Nucleoside phosphoramidate prodrugs

0001This application applies to US Provisional Application No. 60 / 909,315 filed March 30, 2007, US Application No. 60 / 982,309 filed October 24, 2007, and US Application No. 12 / file filed March 21, 2008. Claim priority over 053,015. The contents of each of the above applications are incorporated herein by reference in their entirety.

0002The present invention relates to nucleoside phosphoramidates and their use as agents for treating viral diseases. These compounds are inhibitors of RNA-dependent RNA virus replication and are useful as inhibitors of HCV NS5B polymerase, as inhibitors of HCV replication, and in the treatment of hepatitis C infections in mammals. The present invention provides novel chemical compounds and uses of these compounds for the treatment of HCV infections, alone or in combination with other antiviral agents.

0003Hepatitis C virus (HCV) infection is a serious health problem that causes chronic liver disease such as cirrhosis and hepatocellular carcinoma in a significant number of infected people, estimated to be 2-15% of the world's population. According to the US Centers for Disease Control and Prevention, there are an estimated 4.5 million infected people in the United States alone. According to the World Health Organization, there are more than 200 million infected people worldwide, with at least 3-4 million people infected each year. When infected, about 20% of people eliminate the virus, but the rest can carry HCV until death. Ultimately, 10 to 20 percent of chronically infected people develop liver-destroying cirrhosis or cancer. Viral diseases are transmitted parenterally or sexually by contaminated blood or blood products, contaminated needles, and vertically from infected or carrier mothers to their offspring. Current treatments for HCV infections are limited to immunotherapy with recombinant interferon α alone or in combination with the nucleoside analog ribavirin, with limited clinical utility. Moreover, there is no established vaccine against HCV. For this reason, there is an urgent need for improved therapeutic agents that effectively treat chronic HCV infections. HCV virion is a positive-strand RNA virus with a single-stranded oligoribonucleotide genome sequence of about 9600 bases, which encodes a polyprotein of about 3,010 amino acids. The protein product of the HCV gene consists of structural proteins C, E1, and E2, and the nonstructural proteins NS2, NS3, NS4A, and NS4B, as well as NS5A and NS5B. Non-structured (NS) proteins are thought to provide a catalytic mechanism for viral replication. NS3 protease releases NS5B, an RNA-dependent RNA polymerase, from the polyprotein chain. NS5B polymerase of HCV is required for the synthesis of double-stranded RNA from single-strand viral RNA that serves as a template in the replication cycle of HCV. Therefore, NS5B polymerase is considered to be an essential component in the HCV replication complex (K. Ishi, et al, Hepatology, 1999, 29: 1227-1235, V.I. Lohmann, et al., Virology, 1998, 249: 108-118). Inhibition of the NS5B polymerase of HCV prevents the formation of double-stranded HCV RNA and is therefore an interesting approach for the development of HCV-specific antiviral therapies. HCV belongs to a fairly large family of viruses with many common characteristics.

0004Flaviviridae virus The flaviviridae of the virus is at least three distinct: the genus Pestivirus, which causes diseases in cattle and pigs, the genus Flaviviridae, which is the main cause of diseases such as dengue and yellow fever, and the genus Hepacivirus, whose only member is HCV. It consists of distinguishable genera. The genus Flaviviridae contains more than 68 members, grouped based on serological associations (Calisher et al., J. Gen. Virol, 1993, 70, 37-43). Clinical manifestations are diverse and include fever, encephalitis, and hemorrhagic fever (Fields Virology, Editors: Fields, BN, Knipe, DM, and Howley, PM, Lippincott-Raven Publishers, Philadelphia, PA, 1996, Chapter 31,931-959. ). Globally concerned flaviviruses involved in human disease include dengue hemorrhagic fever virus (DHF), yellow fever virus, shock syndrome, and Japanese encephalitis virus (Halstead, SB, Rev. Infect. Dis., 1984,6,251-264, Halstead, SB, Science, 239: 476-481,1988, Monath, TP, New Eng. J. Med, 1988,319,64 1-643). The genus Pestivirus includes bovine viral diarrhea virus (BVDV), classical swine fever virus (CSFV, also known as cholera virus), and sheep border disease virus (BDV) (Moennig, V. et al. Adv. Vir. Res. 1992, 41, 53-98). Pestivirus infections in livestock (cattle, pigs, and sheep) result in serious, global economic losses. BVDV causes mucosal disease in cattle and has serious economic importance to the livestock industry (Meyers, G. and Thiel, HJ, Advances in Virus Research, 1996, 47, 53-118, Moennig V., et al , Adv. Vir. Res. 1992, 41, 53-98). Human pestivirus is also not as broadly characterized as animal pestivirus. However, serological studies have shown significant pestivirus exposure in humans.

0005Pestivirus and hepacivirus are closely related groups of viruses within the Flaviviridae family. Other closely related viruses within this family include GB virus A, GB virus A-like factor, GB virus-B, and GB virus-C (hepatitis G virus, also known as HGV). The hepacivirus group (hepatitis C virus, HCV) consists of many closely related but genotypically identifiable viruses that infect humans. There are at least 6 HCV genotypes and over 50 subtypes. Due to the similarity between pestivirus and hepacivirus, bovine viral diarrhea virus (BVDV) is often used as an alternative to study HCV virus, coupled with the lack of efficient growth potential of hepacivirus in cell culture. used. The genetic makeup of pestivirus and hepacivirus is very similar. These positive-strand RNA viruses have a single large open reading frame (ORF) that encodes all viral proteins required for viral replication. These proteins are expressed as polyproteins that undergo simultaneous and post-translational processing by both cellular and viral coding proteins to yield mature viral proteins. Viral proteins involved in viral genomic RNA replication are located approximately within the carboxy terminus. Two-thirds of the ORF are referred to as non-structured (NS) proteins. The genetic makeup of pestivirus and hepacivirus, and the polyprotein processing of the nonstructural protein portion of the ORF, are very similar. For both pestivirus and hepacivirus, mature viral (NS) proteins are sequentially from p7, NS2, NS3, NS4A, NS4B, NS5A, and NS5B from the amino terminus of the unstructured protein coding region to the carboxy terminus of the ORF. Become.

0006The NS proteins of pestivirus and hepacivirus share sequence domains that characterize specific protein functions. For example , the NS3 proteins of both groups of viruses have amino acid sequence motifs characteristic of serine proteinase and helicase (Gorbalenya et al., Nature, 1988, 333, 22, Bazan and Fletterick Virology, 1989,171,637-639, Gorbalenya et al., Nucleic Acid Res., 1989, 17, 3889-3897). Similarly, the NS5B proteins of pestivirus and hepacivirus have motifs characteristic of RNA-dependent RNA polymerases (Koonin, EV and Dolja, VV, Crir. Rev. Biochem. Molec. Biol. 1993, 28, 375-430). The actual roles and functions of the pestivirus and hepacivirus NS proteins in the viral life cycle are directly similar. In both cases, NS3 serine proteinase is involved in all proteolytic processing of polyprotein precursor downstream of its position in the ORF (Wiskerchen and Collett, Virology, 1991, 184, 341-350, Bartenschlager et al., J. Virol. 1993, 67, 3835-3844, Eckart et al. Biochem. Biophys. Res. Comm. 1993,192, 399-406, Grakoui et al., J. Virol. 1993, 67, 2832-2843, Grakoui et al., Proc. Natl. Acad Sci. USA 1993, 90, 10583-10587, Hijikata et al., J. Virol. 1993, 67, 4665-4675, Tome et al., J. Virol., 1993, 67, 4017-4026). The NS4A protein acts as a cofactor with the NS3 serine protease in both cases (Bartenschlager et al., J. Virol. 1994, 68, 5045-5055, Failla et al., J. Virol. 1994, 68, 3753. -3760, Xu et al., J. Virol., 1997, 71:53 12-5322). In addition, the NS3 proteins of both viruses function as helicases (Kim et al., Biochem. Biophys. Res. Comm., 1995, 215, 160-166, Jin and Peterson, Arch. Biochem. Biophys., 1995, 323, 47-53, Warrener and Collett, J. Virol. 1995, 69,1720-1726). Finally, the NS5B proteins of pestivirus and hepacivirus have the expected RNA-dependent RNA polymerase activity (Behrens et al., EMBO, 1996, 15, 12-22, Lechmann et al., J. Virol., 1997, 71, 8416-8428, Yuan et al., Biochem. Biophys. Res. Comm. 1997, 232, 231-235, Hagedorn, PCT WO 97/12033, Zhong et al, J. Virol., 1998, 72, 9365-9369). Currently, treatment options for people infected with hepatitis C virus are limited. Currently approved treatment options are the use of immunotherapy with recombinant interferon-α alone or in combination with the nucleoside analog ribavirin. This therapy has limited clinical efficacy and only 50% of treated patients respond to the therapy. Therefore, there is an important need for more effective and novel therapies to address the unmet medical needs raised by HCV infections.

0007Many potential molecules for the discovery of antiviral agents that currently act directly as anti-HCV therapeutics, including, but not limited to, NS2-NS3 autoproteases, N3 proteases, N3 helicases, and NS5B polymerases. The target has been identified. RNA-dependent RNA polymerase is absolutely essential for the replication of single-stranded positive sense RNA genomes, and this enzyme has caused great interest among medicinal chemists. Inhibitors of HCV NS5B are being investigated as potential therapies for HCV infection (Tan, S.-L., et al., Nature Rev. Drug Discov., 2002, 1, 867-881, Walker, MP et al., Exp. Opin. Investigational Drugs, 2003, 12, 1269-1280, Ni, ZJ., Et al., Current Opinion in Drug Discovery and Development, 2004, 7, 446-459, Beaulieu, P. L., et al., Current Opinion in Investigational Drugs, 2004, 5, 838-850, Wu, J., et al., Current Drug Targets-Infectious Disorders, 2003, 3, 207-219, Griffith, RC, et al, Annual Reports in Medicinal Chemistry, 2004, 39, 223-237, Carlol, S., et al., Infectious Disorders-Drug Targets, 2006, 6, 17-29). The potential for the emergence of resistant HCV strains and the need to identify agents with a wide range of genotypes supports the need for continued efforts to identify new and more effective nucleosides as HCV NS5B inhibitors. ..

0008Nucleoside inhibitors of NS5B polymerases can act as either unnatural substrates that result in chain arrest or competitive inhibitors that compete for nucleotide binding to the polymerase. To function as a chain terminator, nucleoside analogs must be taken up by cells and converted to triphosphates in the body to compete for polymerase nucleotide binding sites. This conversion to triphosphate is usually mediated by cellular kinases, which impose additional structural conditions on potential nucleoside polymerase inhibitors. Unfortunately, this limits the direct evaluation of nucleosides as inhibitors of HCV replication for in-situ phosphorylated cell-based assays. In some cases, the biological activity of a nucleoside is hampered by the poor substrate properties of one or more kinases required to convert it to an active triphosphate form. The formation of monophosphate by nucleoside kinases is generally regarded as the rate-determining step of the three phosphorylation events. Preparation of stable phosphate prodrugs has been reported to avoid the need for an early phosphorylation step in the metabolism of nucleosides to active triphosphate analogs. Nucleoside phosphoramidate prodrugs are precursors of active nucleoside triphosphates and have been shown to inhibit viral replication when administered to all virus-infected cells (McGuigan, C., et al., J. Med. Chem., 1996, 39, 1748-1753, Valette, G., et al., J. Med. Chem., 1996, 39, 1981-1990, Balzarini, J., et al ., Proc. National Acad Sci USA, 1996, 93, 7295-7299, Siddiqui, AQ, et al., J. Med. Chem., 1999, 42, 4122-4128, Eisenberg, E. J., et al., Nucleosides, Nucleotides and Nucleic Acids, 2001, 20, 1091-1098, Lee, WA, et al., Antimicrobial Agents and Chemotherapy, 2005, 49, 1898), US Pat. No. 2006/0241064, and International Publication No. WO 2007/095269. Also, limiting the utility of nucleosides as feasible therapeutic agents is their sometimes poor physicochemical and pharmacokinetic properties. These poor properties can limit the intestinal absorption of the drug and limit its uptake into target tissues or cells. Nucleoside prodrugs have been used to improve their properties. Preparation of nucleoside phosphoramidates improves the absorption of nucleosides in the body, and the phosphoramidate portions of these "pronucleotides" are shielded by neutral lipophilic groups to optimize uptake and transport into cells. It has been shown to obtain a partition coefficient suitable for the above and to dramatically increase the intracellular concentration of the nucleoside monophosphate analog as compared with the administration of the parent nucleoside alone. Enzyme-mediated hydrolysis of the phosphate ester moiety produces a nucleoside monophosphate that does not require rate-determining initial phosphorylation.

0009The present invention relates to nucleoside derivatives for the treatment of viral infections in mammals, in the form of compounds, stereoisomers thereof, salts thereof (acid or base addition salts), hydrates, solvates, or crystalline forms. Targeting new phosphoramidate prodrugs, represented by the following structure,<img id="000002" he="50" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />In the formula, (a) R1 is hydrogen, n-alkyl, branched alkyl, cycloalkyl, or aryl, including, but not limited to, phenyl or naphthyl, and phenyl or naphthyl is C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, F, Cl, Br, I, nitro, cyano, C1-6 haloalkyl, -N (R1) 2, C1-6 acylamino, -NHSO2 C1-6 alkyl, Arbitrarily substituted with at least one of -SO2N (R1') 2, COR1'', and -SO2C1-6 alkyl (R1'is independently hydrogen, or alkyl, C1-20 alkyl , C1-10 alkyl, or C1-6 alkyl, but not limited to, R1'' is -OR'or -N (R1') 2), (b) R2 is hydrogen, C1-10 alkyl, such that R3a or R3b and R2 together form a cyclic ring containing adjacent N and C atoms, C (O) CR3aR3bNHR1 (CH2). n, in the formula n is 2 to 4, (c) R3a and R3b are (i) hydrogen, C1-10 alkyl, cycloalkyl,-(CH2) c (NR3') 2, C1-6 hydroxyalkyl, -CH2SH,-(CH2) 2S (O) dMe. ,-(CH2) 3NHC (= NH) NH2,Independently selected from (1H-indole-3-yl) methyl, (1H-imidazol-4-yl) methyl,-(CH2) eCOR3'', aryl, and aryl C1-3 alkyl, the aryl group is Is it optionally substituted with a group selected from hydroxyl, C1-10 alkyl, C1-6 alkoxy, halogen, nitro, and cyano, or (ii) R3a and R3b are both C1-6 alkyl, (iii). ) R3a and R3b are (CH2) f such that they together form a spiro ring, or (iv) R3a is hydrogen and R3b and R2 together contain adjacent N and C atoms. (CH2) n to form a cyclic ring, or (v) R3b to be hydrogen, and R3a and R2 together to form a cyclic ring containing adjacent N and C atoms. (CH2) n, c is 1 to 6, d is 0 to 2, e is 0 to 3, f is 2 to 5, n is 2 to 4, and R3'is , Independently hydrogen or C1-6 alkyl, R3'' is -OR'or -N (R3') 2), or (vi) R3a is H, R3b is H, CH3 , CH2CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, CH2-Indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C (O) NH2, CH2CH2COOH, CH2CH2C (O) NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC (NH) NH2, CH2-imidazol-4-yl, CH2OH, CH (OH) CH3, CH2 ((4'-OH) -Ph), CH2SH, or lower cycloalkyl or (viii) ) R3a is CH3, -CH2CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C (O) NH2, CH2CH2COOH, CH2CH2C (O) NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC (NH) NH2, CH2-imidazol-4-yl, CH2OH, CH (OH) CH3, CH2 ((4'-OH) -Ph), CH2SH, or lower cycloalkyl, where R3b is H And R3'is independently hydrogen or alkyl and includes, but is not limited to, C1-20 alkyl, C1-10 alkyl, or C1-6 alkyl, where R3'' is -OR'. Or -N (R3') 2), (d) R4 is hydrogen, C1-10 alkyl, C1-10 alkyl (optionally substituted with lower alkyl, alkoxy, di (lower alkyl) -amino, or halogen), C1-10 haloalkyl, C3-10 cyclo. Alkoxy, cycloalkylalkyl, cycloheteroalkyl, aminoacyl, aryl (phenyl, etc.), heteroaryl (pyridinyl, etc.), substituted aryl, or substituted heteroaryl. (e) R5 is H, lower alkyl, CN, vinyl, O- (lower alkyl), hydroxyl lower alkyl, i.e.-(CH2) pOH, where p is 1-6 and hydroxylmethyl. Contains (CH2OH), CH2F, N3, CH2CN, CH2NH2, CH2NHCH3, CH2N (CH3) 2, alkynes (optionally substituted), or halogens containing F, Cl, Br, or I, provided that When X is OH, the base is cytosine, R6 is H, R5 cannot be N3, when X is OH, R6 is CH3 or CH2F, B is a purine base. , R5 cannot be H, (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN, (g) X is H, OH, F, OMe, halogen, NH2, or N3, (h) Y is OH, H, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, vinyl, N3, CN, Cl, Br, F, I, NO2, OC (O) O (C1-4) Alkyl), OC (O) O (C1-4 alkyl), OC (O) O (C2-4 alkynyl), OC (O) O (C2-4 alkenyl), OC1-10 haloalkyl, O (aminoacyl), O (C1-10 Acyl), O (C1-4 Alkyl), O (C2-4 Alkenyl), S (C1-4 Acyl), S (C1-4 Alkyl), S (C2-4 Alkinyl), S (C2 -4 alkenyl), SO (C1-4 acyl), SO (C1-4 alkyl), SO (C2-4 alkynyl), SO (C2-4 alkenyl), SO2 (C1-4 acyl), SO2 (C1-4) Alkyl), SO2 (C2-4 alkynyl), SO2 (C2-4 alkenyl), OS (O) 2 (C1-4 acyl), OS (O) 2 (C1-4 alkyl), OS (O) 2 (C2) -4 alkenyl), NH2, NH (C1-4 alkyl), NH (C2-4 alkenyl), NH (C2-4 alkynyl), NH (C1-4 acyl), N (C1-4 alkyl) 2, N ( C1-18 acyl) 2, alkyl, alkynyl, alkenyl, and vinyl are N3, CN, 1 to 3 halogens (Cl, Br, F, I), NO2, C (O) O (C1-4). Alkyl), C (O) O (C1-4 alkyl), C (O) O (C2-4 alkynyl), C (O) O (C2-4 alkenyl), O (C1-4 acyl), O (C1) -4 alkyl), O (C2-4 alkenyl), S (C1-4 acyl), S (C1-4 alkyl), S (C2-4 alkynyl), S (C2-4 alkenyl), SO (C1-4) Acyl), SO (C1-4 alkyl), SO (C2-4 alkynyl), SO (C2-4 alkenyl), SO2 (C1-4 acyl), SO2 (C1-4 alkyl), SO2 (C2-4 alkynyl) , SO2 (C2-4 alkenyl), OS (O) 2 (C1-4 acyl), OS (O) 2 (C1-4 alkyl), OS (O) 2 (C2-4 alkenyl),NH2, NH (C1-4 alkyl), NH (C2-4 alkenyl), NH (C2-4 alkynyl), NH (C1-4 acyl), N (C1-4 alkyl) 2, N (C1-4 acyl) Arbitrarily replaced by 2 The base is a naturally occurring or modified purine or pyrimidine base represented by the following structure.<img id="000003" he="49" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />During the ceremony Z is N or CR12 R7, R8, R9, R10, and R11 are independently lower grades of H, F, Cl, Br, I, OH, OR', SH, SR', NH2, NHR', NR'2, C1-C6. Alkyl, C1-C6 halogenation (F, Cl, Br, I) lower alkyl, C2-C6 lower alkenyl, C2-C6 halogenation (F, Cl, Br, I) lower alkenyl, C2-C6 lower Alkinil<img id="000004" he="6" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />Halogenation of C2-C6 (F, Cl, Br, I) lower alkynyl, lower alkoxy of C1-C6, halogenation of C1-C6 (F, Cl, Br, I) lower alkoxy, CO2H, CO2R', CONH2, CONHR', CONR'2, CH = CHCO2H, or CH = CHCO2R', R'is optionally substituted alkyl, including, but not limited to, optionally substituted C1-20 alkyl, optionally substituted C1-10 alkyl, optionally substituted lower alkyl. , Arbitrarily substituted cycloalkyl, optionally substituted alkynyl of C2-C6, optionally substituted lower alkenyl of C2-C6, or optionally substituted acyl, C (O) alkyl, C Includes, but is not limited to, (O) (C1-20 alkyl), C (O) (C1-10 alkyl), or C (O) (lower alkyl), or, as an alternative, NR'2 , Each R'contains at least one C atom that is linked to form a heterocycle containing at least two carbon atoms. R12 is H, halogen (including F, Cl, Br, I), OH, OR', SH, SR', NH2, NHR', NR'2, NO2, lower alkyl of C1-C6, C1-C6. Halogenated (F, Cl, Br, I) lower alkyl, C2-C6 lower alkenyl, C2-C6 halogenated (F, Cl, Br, I) lower alkynyl, C2-C6 lower alkynyl, C2-C6 Halogenated (F, Cl, Br, I) lower alkynyl, C1-C6 lower alkoxy, C1-C6 halogenated (F, Cl, Br, I) lower alkoxy, CO2H, CO2R', CONH2, CONHR', CONR '2, CH = CHCO2H, or CH = CHCO2R', but when the base is represented by the structure c where R11 is a hydrogen, R12 is (i) -CCH, (ii) -C = Not CH2 or (iii) -NO2.

0010Definition As used herein, the phrase "a" or "an" object refers to one or more of the objects, eg, ("a") compound is one or more compounds or at least one. Refers to one compound. Thus, "a" (or "an"), "one or more", and "at least one" may be used interchangeably herein. The phrase "as defined herein" refers to the first definition provided in the context of the invention. As used herein, the term "arbitrary" or "arbitrarily" may, but does not have to, cause an event or situation described subsequently, the description of which event or situation is. It means that it includes the case where it occurs and the case where it does not occur. For example, "arbitrary bond" means that the bond may or may not be present and the description includes a single bond, a double bond, and a triple bond.

0011The term "independently" is used herein to indicate that a variable applies to any example, without taking into account the existence or nonexistence of the variable having the same or different definition within the same compound. Will be done. Thus, in a compound where R appears twice and is defined as "independently carbon or nitrogen", both R's can be carbon, both R's can be nitrogen, or one R'can be carbon. And the other can be nitrogen. The term "alkenyl" refers to an unsubstituted hydrocarbon chain radical with 2 to 10 carbon atoms having one or two olefin double bonds, preferably one olefin double bond. The term "C2-N alkenyl" refers to an alkenyl containing 2 to N carbon atoms, where N is an integer having the following values, 4, 5, 6, 7, 8, 9, or 10. The term "C2-10 alkenyl" refers to an alkenyl containing 2 to 10 carbon atoms. The term "C2-4 alkenyl" refers to an alkenyl containing 2 to 4 carbon atoms. Examples include, but are not limited to, vinyl, 1-propenyl, 2-propenyl (allyl), or 2-butenyl (crotyl).

0012The term "halogenated alkenyl" refers to an alkenyl containing at least one of F, Cl, Br, and I. The term "alkyl" refers to a saturated monovalent hydrocarbon residue of a non-branched or branched chain containing 1 to 30 carbon atoms. The term "C1-M alkyl" means that M has the following values: 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, Refers to an alkyl containing 1 to M carbon atoms, which is an integer having 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30. The term "C1-4 alkyl" refers to an alkyl containing 1 to 4 carbon atoms. The term "lower alkyl" refers to straight or branched chain hydrocarbon residues containing 1 to 6 carbon atoms. As used herein, "C1-20 alkyl" refers to an alkyl containing 1 to 20 carbon atoms. As used herein, "C1-10 alkyl" refers to an alkyl containing 1 to 10 carbons. Examples of alkyl groups include lower alkyl groups including methyl, ethyl, propyl, i-propyl, n-butyl, i-butyl, t-butyl or pentyl, isopentyl, neopentyl, hexyl, heptyl, and octyl. , Not limited to these. (Al) alkyl or (heteroaryl) alkyl indicates that the alkyl group is optionally substituted with an aryl or heteroaryl group, respectively.

0013The term "cycloalkyl" means that the carbon ring contains 3 to 10 carbon atoms, preferably 3 to 8 carbon atoms, more preferably 3 to 6 carbon atoms (ie, lower cycloalkyl). Refers to a substituted or substituted carbocycle. Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, 2-methyl-cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. The term "cycloalkylalkyl" refers to an unsubstituted or substituted alkyl further substituted by a lower cycloalkyl. Examples of cycloalkylalkyl include cyclopropyl, 2-methyl-cyclopropyl, cyclobutyl, cyclopentyl, and methyl, ethyl, propyl, i-propyl, n-butyl, i-butyl, t-butyl or substituted with cyclohexyl. Includes, but is not limited to, any one of, but is not limited to, pentyl, isopentyl, neopentyl, hexyl, heptyl, octyl.

0014The term "cycloheteroalkyl" refers to an unsubstituted or substituted heterocycle in which the heterocycle contains 2 to 9 carbon atoms, preferably 2 to 7 carbon atoms, more preferably 2 to 5 carbon atoms. Point. Examples of cycloheteroalkyl include aziridine-2-yl, N-C1-3-alkyl-aziridine-2-yl, azetidineyl, N-C1-3-alkyl-azetidine-m'-yl, pyrrolidine-m'- Includes, but is not limited to, yl, N-C1-3-alkyl-pyrrolidin-m'-yl, piperidine-m'-yl, and N-C1-3-alkyl-piperidine-m'-yl. In the formula, m'is 2, 3, or 4 due to cycloheteroalkyl. Specific examples of N-C1-3-alkyl-cycloheteroalkyl include N-methyl-aziridin-2-yl, N-methyl-azetidine-3-yl, N-methyl-pyrridine-3-yl, and N-methyl. -Includes, but is not limited to, pyrrolidine-4-yl, N-methyl-piperidine-2-yl, N-methyl-piperidine-3-yl, and N-methyl-piperidine-4-yl. In the case of R4, the point of attachment between the cycloheteroalkyl ring carbon and oxygen occurs at any one of the m'locations. The term "heterocycle" comprises carbon, hydrogen, and at least one of N, O, and S, where C and N can be trivalent or tetravalent, ie sp2- or sp3-hybridized. Refers to an unsubstituted or substituted heterocycle. Examples of heterocycles include, but are not limited to, aziridine, azetidine, pyrrolidine, piperidine, imidazole, oxazole, piperazine and the like. In the case of piperazine, in relation to R10 for NR'2, the corresponding opposite nitrogen atom of piperazinyl is replaced by a lower alkyl represented by the structure below.<img id="000005" he="20" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />Preferably, the nitrogen opposite to piperazinyl is replaced by a methyl group.

0015The term "alkyl halide" (or "haloalkyl") refers to a non-branched or branched chain alkyl containing at least one of F, Cl, Br, and I. The term "C1-M haloalkyl" refers to an alkyl containing 1 to M carbon atoms, including at least one of F, Cl, Br, and I, where M is the next value, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, An integer with 29, or 30. "C1-3 haloalkyl" refers to a haloalkyl containing 1 to 3 carbons and at least one of F, Cl, Br, and I. The term "lower alkyl halide" (or "lower haloalkyl") refers to a haloalkyl containing 1 to 6 carbon atoms and at least one of F, Cl, Br, and I. Examples include fluoromethyl, chloromethyl, bromomethyl, iodomethyl, difluoromethyl, dichloromethyl, dibromomethyl, diiodomethyl, trifluoromethyl, trichloromethyl, tribromomethyl, triiodomethyl, 1-fluoroethyl, 1-chloroethyl, 1 -Bromoethyl, 1-iodoethyl, 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 2-iodoethyl, 2,2-difluoroethyl, 2,2-dichloroethyl, 2,2-dibromomethyl, 2-2-diiodomethyl , 3-Fluoropropyl, 3-Chloropropyl, 3-Bromopropyl, 2,2,2-trifluoroethyl or 1,1,2,2,2-pentafluoroethyl, but not limited to these. The term "alkynyl" refers to a non-branched or branched hydrocarbon chain radical having 2 to 10 carbon atoms, preferably 2 to 5 carbon atoms and having one triple bond. The term "C2-N alkynyl" refers to an alkynyl containing 2 to N carbon atoms, where N is an integer with the following values: 3, 4, 5, 6, 7, 8, 9, or 10. .. The term "C2-4 alkynyl" refers to an alkynyl containing 2 to 4 carbon atoms. The term "C2-10 alkynyl" refers to an alkynyl containing 2 to 10 carbons. Examples include, but are not limited to, ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, or 3-butynyl.

0016The term "alkynyl halide" has 2 to 10 carbon atoms, preferably 2 to 5 carbon atoms, with one triple bond and at least one of F, Cl, Br, and I. Refers to a non-branched or branched hydrocarbon chain radical having. The term "cycloalkyl" refers to a saturated carbon ring containing 3 to 8 carbon atoms, namely cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl. As used herein, the term "C3-7 cycloalkyl" refers to a cycloalkyl containing 3 to 7 carbons in the carbocycle.

0017The term "alkoxy" refers to an -O-alkyl group or an -O-cycloalkyl group, as alkyl and cycloalkyl are as defined above. Examples of -O-alkyl groups include, but are not limited to, methoxy, ethoxy, n-propyloxy, i-propyloxy, n-butyloxy, i-butyloxy, t-butyloxy. As used herein, "lower alkoxy" refers to an alkoxy group with a "lower alkyl" group as already defined. "C1-10 Alkoxy" refers to -O-alkyl in which the alkyl is C1-10. Examples of -O-cycloalkyl groups include, but are not limited to, -Oc-propyl, -Oc-butyl, -Oc-pentyl, and -Oc-hexyl. The term "halogenated alkoxy" refers to an -O-alkyl group in which the alkyl group comprises any one of F, Cl, Br, and I.

0018The term "halogenated lower alkoxy" refers to an -O- (lower alkyl) group in which the lower alkyl group comprises any one of F, Cl, Br, and I. The term "amino acid" includes naturally occurring and synthetic α, β, γ, or δ amino acids and is found in proteins such as glycine, alanine, valine, leucine, isoleucine, methionine, phenylalanine, tryptophan. , Proline, serine, threonine, cysteine, tyrosine, aspartic acid, glutamine, aspartic acid, glutamic acid, lysine, arginine, and histidine. In a preferred embodiment, the amino acids are in the L configuration. Alternatively, the amino acids are alanyl, valinyl, leucinyl, isoleucinyl, prolinyl, phenylalanyl, tryptophanyl, methioninyl, glycinyl, serinyl, threoninyl, cystenyl, tyrosinyl, asparaginyl, glutaminyl, aspartoyl, glutaroyl, lysynyl, arginyl, histidine β. Alanil, β-valinyl, β-leucynyl, β-isoleucynyl, β-prolinyl, β-phenylalanyl, β-tryptophanyl, β-methioninyl, β-glycinyl, β-serinyl, β-threoninyl, β-cystenyl, β- It can be a derivative of tyrosinyl, β-asparaginyl, β-glutaminyl, β-aspartyl, β-glutaroyl, β-ricinyl, β-arginyl, or β-histidinyl. When the term amino acid is used, α, β, γ, or δ glycine, alanine, valine, leucine, isoleucine, methionine, phenylalanine, tryptophan, proline, serine, threonine, cysteine, tyrosine, aspartin, glutamine, aspartic acid , Glutamic acid, lysine, arginine, and histidine are considered to be specific and independent disclosures of the esters in the D and L configurations, respectively.

0019The term "aminoacyl" includes N, N-unsubstituted, N, N-1 substituted, and N, N-2 substituted derivatives of naturally occurring and synthetic α, β, γ, or δ aminoacyls herein. Aminoacyl is derived from amino acids. Amino-nitrogen can be substituted or unsubstituted. When the amino-nitrogen is substituted, the nitrogen is either a 1- or 2-substitution and the substituent attached to the amino-nitrogen is a lower alkyl or alkaline. When it is used for Y, the expression "O (aminoacyl)" is used. It is understood that the C3'carbon of ribose is bound to the oxygen "O" and then to the carbonyl carbon of the aminoacyl. The term "alkylamino" or "arylamino" refers to an amino group having one or two alkyl or aryl substituents, respectively.

0020The term "protection" as used herein, and unless otherwise defined, refers to a group added to an oxygen, nitrogen, or phosphorus atom to prevent further reaction or for other purposes. A wide variety of oxygen and nitrogen protecting groups are known to those skilled in the art of organic synthesis. Non-limiting examples include C (O) -alkyl, C (O) Ph, C (O) aryl, CH3, CH2-alkyl, CH2-alkenyl, CH2Ph, CH2-aryl, CH2O-alkyl, CH2O-aryl, SO2. Includes -alkyl, SO2-aryl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, and 1,3- (1,1,3,3-tetraisopropyldisyloxanilidene). The term "aryl" as used herein and unless otherwise specified, refers to substituted or unsubstituted phenyl (Ph), biphenyl, or naphthyl, preferably the term aryl is substituted or unsubstituted phenyl. Point to. Aryl groups are, for example, TW Greene and PGM Wuts,'' Protective Groups in Organic Synthesis,'' 3rd ed., John Wiley &amp; Sons, 1999, known to those skilled in the art, either unprotected or protected as needed, hydroxyl, One or more selected from F, Cl, Br, I, amino, alkylamino, arylamino, alkoxy, aryloxy, nitro, cyano, sulfonic acid, sulfate, phosphonic acid, phosphate, and phosphonate. Can be replaced by a part.

0021The term "alkali" or "alkylaryl" refers to an alkyl group with an aryl substituent such as benzyl. The term "aralkyl" or "arylalkyl" refers to an aryl group with an alkyl substituent. The term "di (lower alkyl) amino-lower alkyl" refers to a lower alkyl that is itself substituted with an amino group that is substituted with two lower alkyl groups. Examples include, but are not limited to, (CH3) 2NCH2, (CH3) 2NCH2CH2, (CH3) 2NCH2CH2CH2, and the like. The above example shows a lower alkyl substituted with an N, N-dimethyl-amino substituent at the terminal carbon atom. These are intended merely as examples and are not intended to limit their meaning to require the term "di (lower alkyl) amino-lower alkyl". It is contemplated that the lower alkyl chain can be replaced with N, N-di (lower alkyl) -amino at any position along the chain, for example with CH3CH (N- (lower alkyl) 2) CH2CH2. is there.

0022The term "halo" as used herein includes chloro, bromo, iodine, and fluoro. The term "acyl" refers to a substituent containing a carbonyl moiety and a non-carbonyl moiety. The carbonyl moiety contains a double bond between the carbonyl carbon and the heteroatom, the heteroatom being selected from O, N, and S. If the heteroatom is N, N is replaced by a lower alkyl. Non-carbonyl moieties include, but are not limited to, linear, branched, or cyclic C1-20 alkyl, C1-10 alkyl, or lower alkyl, linear, branched, and cyclic alkyl, alkoxyalkyls including methoxymethyl, benzyls. Aralkyl containing aralkyl, aryloxyalkyl such as phenoxymethyl, or aryl, methanesulfonyl containing phenyl optionally substituted with halogen (F, Cl, Br, I), hydroxyl, C1 to C4 alkyl, or C1 to C4 alkoxy. Selected from sulfonic acid esters such as alkyl or aralkylsulfonyls, including one, two or triphosphates, trityl or monomethoxytrityl, substituted benzyls, trialkylsilyls (eg dimethyl-t-butylsilyl), or diphenylmethylsilyls. .. When at least one aryl group is present in the non-carbonyl moiety, the aryl group preferably comprises a phenyl group. The term "lower acyl" refers to an acyl group whose non-carbonyl moiety is a lower alkyl. The terms "purine" or "pyrimidine" base are adenine, N6-alkylpurine, N6-acylpurine (acyl is C (O) (alkyl, aryl, alkylaryl, or arylalkyl), N6-benzylpurine, N6. -Halopurine, N6-vinylpurine, N6-acetylenepurine, N6-acylpurine, N6-hydroxyalkylpurine, N6-alkylaminopurine, N6-thioalkylpurine, N2-alkylpurine, N2-alkyl-6-thiopurine, pyrimidine, 6-azapyrimidine, including citocin, 5-fluorocitosine, 5-methylcytosine, 6-azacitosine, 2- and / or 4-mercaptopyrimidine, uracil, 5-halouracil containing 5-fluorouracil, C5-alkylpyrimidine, C5- Benzylpyrimidine, C5-halopyrimidine, C5-vinylpyrimidine, C5-acetylenepyrimidine, C5-acylpyrimidine, C5-hydroxyalkylpurine, C5-amidepyrimidine, C5-cyanopyrimidine, C5-iodopyrimidine, C6-iodo-pyrimidine, C5-Br-vinylpyrimidine, C6-Br-vinylpyrimidine, C5-nitropyrimidine, C5-amino-pyrimidine, N2-alkylpurine, N2-alkyl-6-thiopurine, 5-azacitidinyl, 5-azaurasilyl, triazolopyrimidine Includes, but is not limited to, le, imidazolopyrimidine, pyrrolopyrimidinenyl, and pyrazolopyrimidinel. Purine bases include, but are, guanine, adenine, hypoxanthin, 2,6-diaminopurine, and 6-chloropurine. The oxygen and nitrogen functional groups on the base can be protected as needed or desired. Suitable protective groups are well known to those skilled in the art and are known to those skilled in the art and are trimethylsilyl, dimethylhexylsilyl, t-butyldimethylsilyl. , And t-butyldiphenylsilyl, trityl, alkyl groups, and acyl groups such as acetyl and propionyl, methanesulfonyl, and p-toluenesulfonyl.

0023The terms "tautomer" and "tautomer" have their generally accepted plain meaning. The term "P *" refers to the corresponding Cahn-Ingold-Prelog representation of "R" or "S", where the phosphorus atoms are antipodal and have their generally accepted plain meaning. Means to have. It is contemplated that the compounds of formula I are racemic due to their chirality in phosphorus. Applicants intend to use racemates and / or isolated enantiomers. In some cases, the star does not appear next to the phosphoramidaterin atom. In these cases, the phosphorus atom is chiral, and one of ordinary skill in the art will appreciate this unless the substituent attached to the phosphorus eliminates the possibility of chirality in phosphorus, as in P (O) Cl3. It is understood to understand that it is.

0024One aspect of the present invention targets a compound represented by the formula I, a salt thereof, a hydrate, a solvate, a crystal form, and the like.<img id="000006" he="40" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />During the ceremony (a) R1 is hydrogen, n-alkyl, branched alkyl, cycloalkyl, or aryl, including, but not limited to, phenyl or naphthyl, where phenyl or naphthyl is C1-6 alkyl, C2-6. Alkenyl, C2-6 alkynyl, C1-6 alkoxy, F, Cl, Br, I, nitro, cyano, C1-6 haloalkyl, -N (R1) 2, C1-6 acylamino, -NHSO2 C1-6 alkyl, -SO2N ( Arbitrarily substituted with at least one of R1') 2, COR1'', and -SO2C1-6 alkyl (R1'is independently hydrogen, or alkyl, C1-20 alkyl, C1- Includes, but is not limited to, 10 alkyl, or C1-6 alkyl, where R1'' is -OR'or -N (R1') 2), (b) R2 is hydrogen, C1-10 alkyl, such that R3a or R3b and R2 together form a cyclic ring containing adjacent N and C atoms, C (O) CR3aR3bNHR1 (CH2). n, in the formula n is 2 to 4, (c) R3a and R3b are (i) hydrogen, C1-10 alkyl, cycloalkyl,-(CH2) c (NR3') 2, C1-6 hydroxyalkyl, -CH2SH,-(CH2) 2S (O) dMe. ,-(CH2) 3NHC (= NH) NH2,Independently selected from (1H-indole-3-yl) methyl, (1H-imidazol-4-yl) methyl,-(CH2) eCOR3'', aryl, and aryl C1-3 alkyl, the aryl group is Is it optionally substituted with a group selected from hydroxyl, C1-10 alkyl, C1-6 alkoxy, halogen, nitro, and cyano, or (ii) R3a and R3b are both C1-6 alkyl, (iii). ) R3a and R3b are (CH2) f such that they together form a spiro ring, or (iv) R3a is hydrogen and R3b and R2 together contain adjacent N and C atoms. (CH2) n to form a cyclic ring, or (v) R3b to be hydrogen, and R3a and R2 together to form a cyclic ring containing adjacent N and C atoms. (CH2) n, c is 1 to 6, d is 0 to 2, e is 0 to 3, f is 2 to 5, n is 2 to 4, and R3'is , Independently hydrogen or C1-6 alkyl, R3'' is -OR'or -N (R3') 2), or (vi) R3a is H, R3b is H, CH3 , CH2CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, CH2-Indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C (O) NH2, CH2CH2COOH, CH2CH2C (O) NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC (NH) NH2, CH2-imidazol-4-yl, CH2OH, CH (OH) CH3, CH2 ((4'-OH) -Ph), CH2SH, or lower cycloalkyl or (viii) ) R3a is CH3, -CH2CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C (O) NH2, CH2CH2COOH, CH2CH2C (O) NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC (NH) NH2, CH2-imidazol-4-yl, CH2OH, CH (OH) CH3, CH2 ((4'-OH) -Ph), CH2SH, or lower cycloalkyl, where R3b is H And R3'is independently hydrogen or alkyl and includes, but is not limited to, C1-20 alkyl, C1-10 alkyl, or C1-6 alkyl, where R3'' is -OR'. Or -N (R3') 2), (d) R4 is hydrogen, C1-10 alkyl, C1-10 alkyl (optionally substituted with lower alkyl, alkoxy, di (lower alkyl) -amino, or halogen), C1-10 haloalkyl, C3-10 cyclo. Alkoxy, cycloalkylalkyl, cycloheteroalkyl, aminoacyl, aryl (phenyl, etc.), heteroaryl (pyridinyl, etc.), substituted aryl, or substituted heteroaryl. (e) R5 is H, lower alkyl, CN, vinyl, O- (lower alkyl), hydroxyl lower alkyl, i.e.-(CH2) pOH, where p is 1-6 and hydroxylmethyl. Contains (CH2OH), CH2F, N3, CH2CN, CH2NH2, CH2NHCH3, CH2N (CH3) 2, alkynes (optionally substituted), or halogens containing F, Cl, Br, or I, provided that When X is OH, the base is cytosine, R6 is H, R5 cannot be N3, when X is OH, R6 is CH3 or CH2F, B is a purine base. , R5 cannot be H, (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN, (g) X is H, OH, F, OMe, halogen, NH2, or N3, (h) Y is OH, H, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, vinyl, N3, CN, Cl, Br, F, I, NO2, OC (O) O (C1-4) Alkyl), OC (O) O (C1-4 alkyl), OC (O) O (C2-4 alkynyl), OC (O) O (C2-4 alkenyl), OC1-10 haloalkyl, O (aminoacyl), O (C1-10 Acyl), O (C1-4 Alkyl), O (C2-4 Alkenyl), S (C1-4 Acyl), S (C1-4 Alkyl), S (C2-4 Alkinyl), S (C2 -4 alkenyl), SO (C1-4 acyl), SO (C1-4 alkyl), SO (C2-4 alkynyl), SO (C2-4 alkenyl), SO2 (C1-4 acyl), SO2 (C1-4) Alkyl), SO2 (C2-4 alkynyl), SO2 (C2-4 alkenyl), OS (O) 2 (C1-4 acyl), OS (O) 2 (C1-4 alkyl), OS (O) 2 (C2) -4 alkenyl), NH2, NH (C1-4 alkyl), NH (C2-4 alkenyl), NH (C2-4 alkynyl), NH (C1-4 acyl), N (C1-4 alkyl) 2, N ( C1-18 acyl) 2, alkyl, alkynyl, alkenyl, and vinyl are N3, CN, 1 to 3 halogens (Cl, Br, F, I), NO2, C (O) O (C1-4). Alkyl), C (O) O (C1-4 alkyl), C (O) O (C2-4 alkynyl), C (O) O (C2-4 alkenyl), O (C1-4 acyl), O (C1) -4 alkyl), O (C2-4 alkenyl), S (C1-4 acyl), S (C1-4 alkyl), S (C2-4 alkynyl), S (C2-4 alkenyl), SO (C1-4) Acyl), SO (C1-4 alkyl), SO (C2-4 alkynyl), SO (C2-4 alkenyl), SO2 (C1-4 acyl), SO2 (C1-4 alkyl), SO2 (C2-4 alkynyl) , SO2 (C2-4 alkenyl), OS (O) 2 (C1-4 acyl), OS (O) 2 (C1-4 alkyl), OS (O) 2 (C2-4 alkenyl),NH2, NH (C1-4 alkyl), NH (C2-4 alkenyl), NH (C2-4 alkynyl), NH (C1-4 acyl), N (C1-4 alkyl) 2, N (C1-4 acyl) Arbitrarily replaced by 2 The base is a naturally occurring or modified purine or pyrimidine base represented by the following structure.<img id="000007" he="49" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />During the ceremony Z is N or CR12 R7, R8, R9, R10, and R11 are independently lower grades of H, F, Cl, Br, I, OH, OR', SH, SR', NH2, NHR', NR'2, C1-C6. Alkyl, C1-C6 halogenation (F, Cl, Br, I) lower alkyl, C2-C6 lower alkenyl, C2-C6 halogenation (F, Cl, Br, I) lower alkenyl, C2-C6 lower Alkinil<img id="000008" he="6" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />Halogenation of C2-C6 (F, Cl, Br, I) lower alkynyl, lower alkoxy of C1-C6, halogenation of C1-C6 (F, Cl, Br, I) lower alkoxy, CO2H, CO2R', CONH2, CONHR', CONR'2, CH = CHCO2H, or CH = CHCO2R', R'is optionally substituted alkyl, including, but not limited to, optionally substituted C1-20 alkyl, optionally substituted C1-10 alkyl, optionally substituted lower alkyl. , Arbitrarily substituted cycloalkyl, optionally substituted alkynyl of C2-C6, optionally substituted lower alkenyl of C2-C6, or optionally substituted acyl, C (O) alkyl, C Includes, but is not limited to, (O) (C1-20 alkyl), C (O) (C1-10 alkyl), or C (O) (lower alkyl), or, as an alternative, NR'2 , Each R'contains at least one C atom that is linked to form a heterocycle containing at least two carbon atoms. R12 is H, halogen (including F, Cl, Br, I), OH, OR', SH, SR', NH2, NHR', NR'2, NO2, lower alkyl of C1-C6, C1-C6. Halogenated (F, Cl, Br, I) lower alkyl, C2-C6 lower alkenyl, C2-C6 halogenated (F, Cl, Br, I) lower alkynyl, C2-C6 lower alkynyl, C2-C6 Halogenated (F, Cl, Br, I) lower alkynyl, C1-C6 lower alkoxy, C1-C6 halogenated (F, Cl, Br, I) lower alkoxy, CO2H, CO2R', CONH2, CONHR', CONR '2, CH = CHCO2H, or CH = CHCO2R', but when the base is represented by the structure c where R11 is a hydrogen, R12 is (i) -CCH, (ii) -C = Not CH2 or (iii) -NO2.

0025As can be recognized from the structure represented by the above formula I, there are innumerable ways to express some embodiments and aspects of each embodiment of the present invention. As can be seen below, we have disclosed some embodiments for compounds of formula I, each of which has several embodiments, based on the uniqueness of the modified purine or pyrimidine base. .. This is not intended and should not be construed as an explicit or implied approval that the three embodiments are independent or unique. Rather, it is intended to convey information so that the full scope of the invention can be understood. Furthermore, the following embodiments and aspects thereof are not intended to limit the complete scope of the invention listed by the structure of Formula I. The first embodiment of the present invention targets a compound represented by the formula I-1.<img id="000009" he="85" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />During the ceremony (a) R1 is hydrogen, n-alkyl, branched alkyl, cycloalkyl, or aryl, including, but not limited to, phenyl or naphthyl, where phenyl or naphthyl is C1-6 alkyl, C2-6 alkoxy, C2-6 alkynyl, C1-6 alkoxy, F, Cl, Br, I, nitro, cyano, C1-6 haloalkyl, -N (R1) 2, C1-6 acylamino, -NHSO2 C1-6 alkyl, -SO2N (R1' ) 2, COR1'', and -SO2C1-6 alkyl optionally substituted (R1'is independently hydrogen, or alkyl, C1-20 alkyl, C1-10 alkyl , Or including, but not limited to, C1-6 alkyl, where R1'' is -OR'or -N (R1') 2), (b) R2 is hydrogen, C1-10 alkyl, such that R3a or R3b and R2 together form a cyclic ring containing adjacent N and C atoms, C (O) CR3aR3bNHR1 (CH2). n, in the formula n is 2 to 4, (c) R3a and R3b are (i) hydrogen, C1-10 alkyl, cycloalkyl,-(CH2) c (NR3') 2, C1-6 hydroxyalkyl, -CH2SH,-(CH2) 2S (O) dMe. ,-(CH2) 3NHC (= NH) NH2,Independently selected from (1H-indole-3-yl) methyl, (1H-imidazol-4-yl) methyl,-(CH2) eCOR3'', aryl, and aryl C1-3 alkyl, the aryl group is Is it optionally substituted with a group selected from hydroxyl, C1-10 alkyl, C1-6 alkoxy, halogen, nitro, and cyano, or (ii) R3a and R3b are both C1-6 alkyl, (iii). ) R3a and R3b are (CH2) f such that they together form a spiro ring, or (iv) R3a is hydrogen and R3b and R2 together contain adjacent N and C atoms. (CH2) n to form a cyclic ring, or (v) R3b to be hydrogen, and R3a and R2 together to form a cyclic ring containing adjacent N and C atoms. (CH2) n, c is 1 to 6, d is 0 to 2, e is 0 to 3, f is 2 to 5, n is 2 to 4, and R3'is , Independently hydrogen or C1-6 alkyl, R3'' is -OR'or -N (R3') 2), or (vi) R3a is H, R3b is H, CH3 , CH2CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, CH2-Indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C (O) NH2, CH2CH2COOH, CH2CH2C (O) NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC (NH) NH2, CH2-imidazol-4-yl, CH2OH, CH (OH) CH3, CH2 ((4'-OH) -Ph), CH2SH, or lower cycloalkyl or (viii) ) R3a is CH3, -CH2CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C (O) NH2, CH2CH2COOH, CH2CH2C (O) NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC (NH) NH2, CH2-imidazol-4-yl, CH2OH, CH (OH) CH3, CH2 ((4'-OH) -Ph), CH2SH, or lower cycloalkyl, where R3b is H And R3'is independently hydrogen or alkyl and includes, but is not limited to, C1-20 alkyl, C1-10 alkyl, or C1-6 alkyl, where R3'' is -OR'. Or -N (R3') 2), (d) R4 is hydrogen, C1-10 alkyl, C1-10 alkyl (optionally substituted with lower alkyl, alkoxy, di (lower alkyl) -amino, or halogen), C1-10 haloalkyl, C3-10 cyclo. Alkoxy, cycloalkylalkyl, cycloheteroalkyl, aminoacyl, di (lower alkyl) -amino, aryl (phenyl, etc.), heteroaryl (pyridinyl, etc.), substituted aryl, or substituted heteroaryl. (e) R5 is H, lower alkyl, CN, vinyl, O- (lower alkyl), hydroxyl lower alkyl, i.e.-(CH2) pOH, where p is 1-6 and hydroxylmethyl. Contains (CH2OH), CH2F, N3, CH2CN, CH2NH2, CH2NHCH3, CH2N (CH3) 2, alkynes (optionally substituted), or halogens containing F, Cl, Br, or I, provided that When X is OH, the base is cytosine, R6 is H, R5 cannot be N3, when X is OH, R6 is CH3 or CH2F, B is a purine base. , R5 cannot be H, (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN, (g) X is H, OH, F, OMe, Cl, Br, I, NH2, or N3, (h) Y is OH, H, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, vinyl, N3, CN, Cl, Br, F, I, NO2, OC (O) O (C1-4) Alkyl), OC (O) O (C1-4 alkyl), OC (O) O (C2-4 alkynyl), OC (O) O (C2-4 alkenyl), OC1-10 haloalkyl, O (aminoacyl), O (C1-10 Acyl), O (C1-4 Alkyl), O (C2-4 Alkenyl), S (C1-4 Acyl), S (C1-4 Alkyl), S (C2-4 Alkinyl), S (C2 -4 alkenyl), SO (C1-4 acyl), SO (C1-4 alkyl), SO (C2-4 alkynyl), SO (C2-4 alkenyl), SO2 (C1-4 acyl), SO2 (C1-4) Alkyl), SO2 (C2-4 alkynyl), SO2 (C2-4 alkenyl), OS (O) 2 (C1-4 acyl), OS (O) 2 (C1-4 alkyl), OS (O) 2 (C2) -4 alkenyl), NH2, NH (C1-4 alkyl), NH (C2-4 alkenyl), NH (C2-4 alkynyl), NH (C1-4 acyl), N (C1-4 alkyl) 2, N ( C1-18 acyl) 2, alkyl, alkynyl, alkenyl, and vinyl are N3, CN, 1 to 3 halogens (Cl, Br, F, I), NO2, C (O) O (C1-4). Alkyl), C (O) O (C1-4 alkyl), C (O) O (C2-4 alkynyl), C (O) O (C2-4 alkenyl), O (C1-4 acyl), O (C1) -4 alkyl), O (C2-4 alkenyl), S (C1-4 acyl), S (C1-4 alkyl), S (C2-4 alkynyl), S (C2-4 alkenyl), SO (C1-4) Acyl), SO (C1-4 alkyl), SO (C2-4 alkynyl), SO (C2-4 alkenyl), SO2 (C1-4 acyl), SO2 (C1-4 alkyl), SO2 (C2-4 alkynyl) , SO2 (C2-4 alkenyl), OS (O) 2 (C1-4 acyl), OS (O) 2 (C1-4 alkyl), OS (O) 2 (C2-4 alkenyl),NH2, NH (C1-4 alkyl), NH (C2-4 alkenyl), NH (C2-4 alkynyl), NH (C1-4 acyl), N (C1-4 alkyl) 2, N (C1-4 acyl) Arbitrarily replaced by 2 (i) R7, R8, R9 are independently H, F, Cl, Br, I, OH, OR', SH, SR', NH2, NHR', NR'2, lower alkyl, halogenated (F, Cl, Br, I) Lower alkyl, lower alkenyl of C2-C6, CO2H, CO2R', CONH2, CONHR', CONR'2, where R'is C1-20 alkyl, C1-20 cycloalkyl, C2-C6 alkenyl and C2-C6 alkynyl.

0026The first aspect of the first embodiment is directed to a compound of formula I-1. During the ceremony (a) R1 is hydrogen, n-alkyl, or aryl, including, but not limited to, phenyl or naphthyl, where phenyl or naphthyl is C1-6 alkyl, C1-6 alkoxy, F, Cl, Arbitrarily substituted with at least one of Br, I, nitro, cyano, C1-6 haloalkyl, (b) R2 is hydrogen or CH3, (c) R3a and R3b are independent, (i) R3a is hydrogen, and R3b and R2 are (CH2) n such that they together form a cyclic ring containing adjacent N and C atoms. Or (v) R3b is hydrogen, R3a and R2 are (CH2) n such that they together form a cyclic ring containing adjacent N and C atoms, and c is 1-6. d is 0 to 2, e is 0 to 3, f is 3 to 5, n is 2 to 4, R3'is independently hydrogen or C1-6 alkyl, R3' 'Is -OR' or -N (R3') 2) or (vi) R3a is H and R3b is H, CH3, CH (CH3) 2, CH2CH (CH3) 2, CH ( CH3) CH2CH3, CH2Ph, CH2-Indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C (O) NH2, CH2CH2COOH, CH2CH2C (O) NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC (NH) NH2, CH2-Imidazole-4-yl, CH2OH, CH (OH) CH3, CH2 ((4'-OH) -Ph), CH2SH, or lower cycloalkyl, or (viii) R3a is CH3, CH (CH3) 2, CH2CH (CH3) 2 , CH (CH3) CH2CH3, CH2Ph, CH2-Indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C (O) NH2, CH2CH2COOH, CH2CH2C (O) NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC (NH) NH2, CH2-Imidazole -Il, CH2OH, CH (OH) CH3, CH2 ((4'-OH) -Ph), or CH2SH, R3b is H, (d) R4 is hydrogen, C1-10 alkyl, C1-10 alkyl (optionally substituted with lower alkyl, alkoxy, di (lower alkyl) -amino, or halogen), C1-10 haloalkyl, C3-10 cyclo. Alkoxy, cycloalkylalkyl, cycloheteroalkyl, aminoacyl, aryl (phenyl, etc.), heteroaryl (pyridinyl, etc.), substituted aryl, or substituted heteroaryl. (e) R5 is CH2 (halo) such as H, CN, CH3, vinyl, OCH3, OCH2CH3, CH2OH, CH2F, N3, CH2CN, CH2N3, CH2NH2, CH2NHCH3, CH2N (CH3) 2, F, Cl, Br, Or a halogen containing I, provided that when X is OH, the base is cytosine, R6 is H, and R5 cannot be N3. (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN, (g) X is H, OH, F, OMe, Cl, Br, I, NH2, or N3, (h) Y is OH, H, C1-4 alkyl, vinyl, N3, CN, Cl, Br, F, I, O (C1-6 acyl), O (C1-4 alkyl), NH2, NH (C1) -4 alkyl), NH (C2-4 alkenyl), NH (C2-4 alkynyl), NH (C1-4 acyl), N (C1-4 alkyl) 2, N (C1-18 acyl) 2, Alkyl, alkynyl, alkenyl, and vinyl are N3, CN, 1 to 3 halogens (Cl, Br, F, I), NO2, OC (O) O (C1-4 alkyl), OC (O) O (C1). -4 alkyl), OC (O) O (C2-4 alkynyl), OC (O) O (C2-4 alkenyl), OC1-4 haloalkyl, O (aminoacyl), O (C1-4 acyl), O (C1) -4 alkyl), O (C2-4 alkenyl), S (C1-4 acyl), S (C1-4 alkyl), S (C2-4 alkynyl), S (C2-4 alkenyl), SO (C1-4) Acyl), SO (C1-4 alkyl), SO (C2-4 alkynyl), SO (C2-4 alkenyl), SO2 (C1-4 acyl), SO2 (C1-4 alkyl), SO2 (C2-4 alkynyl) , SO2 (C2-4 alkenyl), OS (O) 2 (C1-4 acyl), OS (O) 2 (C1-4 alkyl), OS (O) 2 (C2-4 alkenyl), NH2, NH (C1 -4 Alkyl), NH (C2-4 Alkenyl), NH (C2-4 Alkinyl), NH (C1-4 Acyl), N (C1-4 Alkyl) 2, or N (C1-4 Acyl) 2 optionally Replaced (i) R7, R8, R9 are independently H, F, Cl, Br, I, OH, OR', SH, SR', NH2, NHR', NR'2, lower alkyl, halogenated (F, Cl, Br, I) Lower alkyl, lower alkenyl of C2-C6, CO2H, CO2R', CONH2, CONHR', CONR'2, where R'is C1-20 alkyl, C1-20 cycloalkyl, C2-C6 alkenyl and C2-C6 alkynyl.

0027The second aspect of the first embodiment is directed to a compound of formula I-1. During the ceremony (a) R1 is hydrogen, n-alkyl, or substituted or unsubstituted phenyl, and the substituents of the substituted phenyl are C1-3 alkyl, C1-3 alkoxy, F, Cl, Br, I, nitro, cyano. , And at least one of the C1-3 haloalkyl, (b) R2 is hydrogen or CH3, (c) R3a and R3b are independent, (i) R3a is hydrogen, and R3b and R2 are (CH2) n such that they together form a cyclic ring containing adjacent N and C atoms. Or (v) R3b is hydrogen, R3a and R2 are (CH2) n such that they together form a cyclic ring containing adjacent N and C atoms, and c is 1-6. d is 0 to 2, e is 0 to 3, f is 3 to 5, n is 2 to 4, R3'is independently hydrogen or C1-6 alkyl, R3' 'Is -OR' or -N (R3') 2) or (vi) R3a is H and R3b is H, CH3, CH (CH3) 2, CH2CH (CH3) 2, CH ( CH3) CH2CH3, CH2Ph, CH2-Indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C (O) NH2, CH2CH2COOH, CH2CH2C (O) NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC (NH) NH2, CH2-Imidazole-4-yl, CH2OH, CH (OH) CH3, CH2 ((4'-OH) -Ph), CH2SH, or lower cycloalkyl, or (viii) R3a is CH3, CH (CH3) 2, CH2CH (CH3) 2 , CH (CH3) CH2CH3, CH2Ph, CH2-Indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C (O) NH2, CH2CH2COOH, CH2CH2C (O) NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC (NH) NH2, CH2-Imidazole -Il, CH2OH, CH (OH) CH3, CH2 ((4'-OH) -Ph), or CH2SH, R3b is H, (d) R4 is hydrogen, CH3, Et, iPr, nPr, nBu, 2-butyl, tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridine-2-yl, N-methyl-azetidine. -3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, di (lower alkyl) amino-lower alkyl, or aminoacyl And (e) R5 includes CH2 (halo) such as H, CN, CH3, OCH3, CH2OH, CH2F, N3, CH2CN, CH2N3, CH2NH2, CH2NHCH3, CH2N (CH3) 2, F, Cl, Br, or I. Halogen, provided that when X is OH, the base is cytosine, R6 is H, and R5 cannot be N3. (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN, (g) X is H, OH, F, OCH3, NH2, or N3, (h) Y is OH, H, CH3, vinyl, N3, CN, Cl, Br, F, I, OC (O) CH3, OCH3, NH2, NHCH3, NH (vinyl), NH (acetyl), NH ( C (O) CH3), N (CH3) 2, N (C (O) CH3) 2, or O (aminoacyl), (i) R7 and R8 are independently H, F, Cl, Br, I, OH, OCH3, SH, SCH3, NH2, NHCH3, N (CH3) 2, CH3, CH3-qXq (in the formula, X is F, Cl, Br, or I, q is 1 to 3), vinyl, CO2H, CO2CH3, CONH2, CONHCH3, or CON (CH3) 2, (j) R9 includes, but is limited to, OH, OCH3, SH, SCH3, NH2, NHCH3, N (CH3) 2, OC (O) (C1-20 alkyl) (OC (O) (CH2) sCH3. Not), NHC (O) (C1-20 alkyl) (including, but not limited to, NHC (O) (CH2) sCH3), and N (C (O) (CH2) sCH3) 2 (N (C (C (C) In the formula, s includes, but is not limited to, O) (CH2) sCH3) 2, s is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, It is an integer selected from 13, 14, 15, 16, 17, 18, and 19).

0028A third aspect of the first embodiment is directed to a compound of formula I-1. During the ceremony (a) R1 is hydrogen, n-alkyl, or substituted or unsubstituted phenyl, and substituted or unsubstituted phenyl is CH3, OCH3, F, Cl, Br, I, nitro, cyano, and CH3-qXq ( In the formula, X is F, Cl, Br, or I, and q is 1 to 3). (b) R2 is hydrogen or CH3, (c) R3a is H, R3b is H, CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C (O) NH2, CH2CH2COOH, CH2CH2C (O) NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC (NH) NH2, CH2-imidazol-4-yl, CH2OH, CH (OH) CH3, CH2 ((4'-OH) -Ph) , CH2SH, or lower cycloalkyl, or R3a is CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C (O) NH2, CH2CH2COOH, CH2CH2C (O) NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC (NH) NH2, CH2-imidazol-4-yl, CH2OH, CH (OH) CH3, CH2 ((4'-OH) -Ph) , CH2SH, or lower cycloalkyl, R3b is H, (d) R4 is hydrogen, CH3, Et, iPr, nPr, nBu, 2-butyl, tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridine-2-yl, N-methyl-azetidine. -3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, lower haloalkyl, di (lower alkyl) amino-lower alkyl, or aminoacyl, (e) R5 includes CH2 (halo) such as H, CN, CH3, OCH3, CH2OH, CH2F, N3, CH2CN, CH2N3, CH2NH2, CH2NHCH3, CH2N (CH3) 2, F, Cl, Br, or I. Halogen, provided that when X is OH, the base is cytosine, R6 is H, and R5 cannot be N3. (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN, (g) X is H, OH, F, OCH3, NH2, or N3, (h) Y is OH, H, CH3, vinyl, N3, CN, Cl, Br, F, I, OC (O) CH3, OCH3, NH2, NHCH3, NH (vinyl), NH (acetyl), NH ( C (O) CH3), N (CH3) 2, N (C (O) CH3) 2, or O (aminoacyl), (i) R7 and R8 are independently H, F, Cl, Br, I, OH, OCH3, SH, SCH3, NH2, NHCH3, N (CH3) 2, CH3, CH3-qXq (in the formula, X is F, Cl, Br, or I, q is 1 to 3), vinyl, CO2H, CO2CH3, CONH2, CONHCH3, or CON (CH3) 2, where R'is C1-20 alkyl, C1- 20 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl', (j) R9 includes, but is limited to, OH, OCH3, SH, SCH3, NH2, NHCH3, N (CH3) 2, OC (O) (C1-20 alkyl) (OC (O) (CH2) sCH3. Not), NHC (O) (C1-20 alkyl) (including, but not limited to, NHC (O) (CH2) sCH3), and N (C (O) (CH2) sCH3) 2 (N (C (C (C) In the formula, s includes, but is not limited to, O) (CH2) sCH3) 2, s is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, It is an integer selected from 13, 14, 15, 16, 17, 18, and 19).

0029The fourth aspect of the first embodiment targets the compound represented by the formula I-2.<img id="000010" he="89" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />During the ceremony (a) R1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, or substituted or unsubstituted phenyl, and substituted or unsubstituted phenyl is CH3, OCH3, F, Cl, Br, I, nitro. , Cyano, and CH3-qXq (in the formula, X is F, Cl, Br, or I, q is 1-3), (b) R2 is hydrogen or CH3, (c) R3a is H, R3b is H, CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C (O) NH2, CH2CH2COOH, CH2CH2C (O) NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC (NH) NH2, CH2-imidazol-4-yl, CH2OH, CH (OH) CH3, CH2 ((4'-OH) -Ph) , CH2SH, or lower cycloalkyl, or R3a is CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C (O) NH2, CH2CH2COOH, CH2CH2C (O) NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC (NH) NH2, CH2-imidazol-4-yl, CH2OH, CH (OH) CH3, CH2 ((4'-OH) -Ph) , CH2SH, or lower cycloalkyl, R3b is H, (d) R4 is hydrogen, C1-10 alkyl, C1-10 alkyl (optionally substituted with lower alkyl, alkoxy, or halogen), C1-10 haloalkyl, C3-10 cycloalkyl, cycloalkylalkyl, cyclohetero. Alkoxy, aminoacyl, di (lower alkyl) amino-lower alkyl, aryl (phenyl, etc.), heteroaryl (pyridinyl, etc.), substituted aryl, or substituted heteroaryl. (e) R5 is a halogen containing H, CN, CH3, OCH3, CH2OH, CH2F, N3, CH2CN, CH2N3, CH2NH2, CH2NHCH3, CH2N (CH3) 2, F, Cl, Br, or I. , On the condition that when X is OH, the base is cytosine, R6 is H, and R5 cannot be N3. (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN, (g) X is H, OH, F, OCH3, Cl, Br, I, NH2, or N3, (h) Y is OH, H, CH3, vinyl, N3, CN, Cl, Br, F, I, OC (O) CH3, OCH3, NH2, NHCH3, NH (vinyl), NH (acetyl), NH ( C (O) CH3), N (CH3) 2, N (C (O) CH3) 2, or O (aminoacyl), (i) R7 and R8 are independently H, F, Cl, Br, I, OH, OCH3, SH, SCH3, NH2, NHCH3, N (CH3) 2, CH3, CH3-qXq (in the formula, X is F, Cl, Br, or I, q is 1 to 3), vinyl, CO2H, CO2CH3, CONH2, CONHCH3, or CON (CH3) 2, where R'is C1-20 alkyl, C1- 20 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, (j) R9 includes, but is limited to, OH, OCH3, SH, SCH3, NH2, NHCH3, N (CH3) 2, OC (O) (C1-20 alkyl) (OC (O) (CH2) sCH3. Not), NHC (O) (C1-20 alkyl) (including, but not limited to, NHC (O) (CH2) sCH3), and N (C (O) (CH2) sCH3 (N (C (O)) In the formula, s includes, but is not limited to, (CH2) sCH3) 2, s is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, It is an integer selected from 14, 15, 16, 17, 18, and 19). A fifth aspect of the first embodiment is directed to a compound of formula I-2. During the ceremony (a) R1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl, (b) R2 is hydrogen or CH3, (c) R3a is H, R3b is H, CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, CH2-indole-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C (O) NH2, CH2CH2COOH, CH2CH2C (O) NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC (NH) NH2, CH2-imidazol-4-yl, CH2OH, CH (OH) CH3, CH2 ((4'-OH) -Ph) , CH2SH, or lower cycloalkyl, (d) R4 is hydrogen, CH3, Et, iPr, nPr, nBu, 2-butyl, tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridine-2-yl, N-methyl-azetidine. -3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, lower haloalkyl, di (lower alkyl) amino-lower alkyl, or aminoacyl, (e) R5 is a halogen containing H, CN, CH3, OCH3, CH2OH, CH2F, F, Cl, Br, or I. (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN, (g) X is H, OH, F, OCH3, NH2, or N3, (h) Y is OH, H, CH3, vinyl, N3, CN, Cl, Br, F, I, OC (O) CH3, OCH3, or O (aminoacyl). (i) R7 and R8 are independently H, F, Cl, Br, I, OH, OCH3, SH, SCH3, NH2, NHCH3, N (CH3) 2, CH3, CH3-qXq (in the formula, X is F, Cl, Br, or I, q is 1 to 3), vinyl, CO2H, CO2CH3, CONH2, CONHCH3, or CON (CH3) 2, where R'is C1-20 alkyl, C1- 20 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, (j) R9 includes, but is limited to, OH, OCH3, SH, SCH3, NH2, NHCH3, N (CH3) 2, OC (O) (C1-20 alkyl) (OC (O) (CH2) sCH3. Not), NHC (O) (C1-20 alkyl) (including, but not limited to, NHC (O) (CH2) sCH3), and N (C (O) (CH2) sCH3) 2 (N (C (C (C) In the formula, s includes, but is not limited to, O) (CH2) sCH3) 2, s is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, It is an integer selected from 13, 14, 15, 16, 17, 18, and 19).

0030A sixth aspect of the first embodiment is directed to a compound of formula I-2. During the ceremony (a) R1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl, (b) R2 is hydrogen or CH3, (c) R3a is H, R3b is H, CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, or lower cycloalkyl. (d) R4 is hydrogen, C1-10 alkyl, C1-10 alkyl (optionally substituted with lower alkyl, alkoxy, or halogen), C1-10 haloalkyl, C3-10 cycloalkyl, cycloalkylalkyl, cyclohetero. Alkoxy, aminoacyl, di (lower alkyl) amino-lower alkyl, aryl (phenyl, etc.), heteroaryl (pyridinyl, etc.), substituted aryl, or substituted heteroaryl. (e) R5 is H, OMe, CN, CH2F, F, Cl, Br, or I, (f) R6 is H, CH3, CH2F, CHF2, CF3, or F, (g) X is H, OH, F, OCH3, F, Cl, Br, I, or N3, (h) Y is H, OH, CH3, F, Cl, Br, I, or N3, OCH3, OC (O) CH3, or O (aminoacyl). (i) R7 and R8 are independently H, F, Br, SCH3, CH3, CH3-qXq (in the formula, X is F, Cl, Br, or I, q is 1 to 3). , Vinyl, CO2CH3, CONH2, CONHCH3, or CON (CH3) 2, (j) R9 includes, but is limited to, OH, OCH3, SH, SCH3, NH2, NHCH3, N (CH3) 2, OC (O) (C1-20 alkyl) (OC (O) (CH2) sCH3. Not), NHC (O) (C1-20 alkyl) (including, but not limited to, NHC (O) (CH2) sCH3), and N (C (O) (CH2) sCH3) 2 (N (C (C (C) In the formula, s includes, but is not limited to, O) (CH2) sCH3) 2, s is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, It is an integer selected from 13, 14, 15, 16, 17, 18, and 19). A seventh aspect of the first embodiment is directed to a compound of formula I-2. During the ceremony (a) R1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl, (b) R2 is hydrogen, (c) R3a is H, R3b is H, CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, or lower cycloalkyl. (d) R4 is hydrogen, CH3, Et, iPr, nPr, nBu, 2-butyl, tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridine-2-yl, N-methyl-azetidine. -3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di (lower alkyl) amino-lower alkyl , (e) R5 is H, (f) R6 is H, CH3, CH2F, CHF2, CF3, or F, (g) X is H, OH, OCH3, F, or N3, (h) Y is OH, OCH3, OC (O) CH3, or O (aminoacyl). (i) R7 and R8 are independently H, F, Br, SCH3, CH3, CH3-qXq (in the formula, X is F, Cl, Br, or I, q is 1 to 3). , Vinyl, CO2CH3, CONH2, CONHCH3, or CON (CH3) 2, (j) R9 includes, but is not limited to, OH, OCH3, NH2, NHCH3, N (CH3) 2, OC (O) (C1-20 alkyl) (including, but not limited to, OC (O) (CH2) sCH3). (O) (C1-20 alkyl) (including, but not limited to, NHC (O) (CH2) sCH3), and N (C (O) (CH2) sCH3) 2 (N (C (O) (CH2) ) SCH3) 2, but not limited to, in the formula, s is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, It is an integer selected from 15, 16, 17, 18, and 19).

0031The eighth aspect of the first embodiment is directed to the compound represented by the formula I-2. During the ceremony (a) R1 is hydrogen, methyl, phenyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl, (b) R2 is hydrogen, (c) R3a is H, R3b is H, CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, or lower cycloalkyl. (d) R4 is hydrogen, CH3, Et, iPr, nPr, nBu, 2-butyl, tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridine-2-yl, N-methyl-azetidine. -3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di (lower alkyl) amino-lower alkyl , (e) R5 is H, (f) R6 is H, CH3, CH2F, CHF2, CF3, or F, (g) X is H, OH, OCH3, F, or N3, (h) Y is OH, OCH3, OC (O) CH3, or O (aminoacyl). (i) R7 and R8 are independently H, F, Br, SCH3, CH3, CH3-qXq (in the formula, X is F, Cl, Br, or I, q is 1 to 3). , Vinyl, CO2CH3, CONH2, CONHCH3, or CON (CH3) 2, (j) R9 includes, but is not limited to, OH, OCH3, NH2, NHCH3, N (CH3) 2, OC (O) (C1-20 alkyl) (including, but not limited to, OC (O) (CH2) sCH3). (O) (C1-20 alkyl) (including, but not limited to, NHC (O) (CH2) sCH3), and N (C (O) (CH2) sCH3) 2 (N (C (O) (CH2) ) SCH3) 2, but not limited to, in the formula, s is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, It is an integer selected from 15, 16, 17, 18, and 19). The second embodiment of the present invention targets a compound represented by the formula I, in which the base has a structure represented by the above formula b, and has a structure represented by the above formula b, R1, R2, R3a, R3b, R4, R5, R6, X, Y, R7, and R8 are defined in the section of the abstract of the invention above.

0032The first aspect of the second embodiment is directed to a compound of formula I-3.<img id="000011" he="71" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />During the ceremony (a) R1 is hydrogen, n-alkyl, branched alkyl, cycloalkyl, or aryl, including, but not limited to, phenyl or naphthyl, where phenyl or naphthyl is C1-6 alkyl, C2-6 alkoxy, C2-6 alkynyl, C1-6 alkoxy, F, Cl, Br, I, nitro, cyano, C1-6 haloalkyl, -N (R1) 2, C1-6 acylamino, -NHSO2 C1-6 alkyl, -SO2N (R1' ) 2, COR1'', and -SO2C1-6 alkyl optionally substituted (R1'is independently hydrogen, or alkyl, C1-20 alkyl, C1-10 alkyl , Or including, but not limited to, C1-6 alkyl, where R1'' is -OR'or -N (R1') 2), (b) R2 is hydrogen or CH3, (c) R3a and R3b are (i) hydrogen, C1-10 alkyl, cycloalkyl,-(CH2) c (NR3') 2, C1-6 hydroxyalkyl, -CH2SH,-(CH2) 2S (O) dMe. ,-(CH2) 3NHC (= NH) NH2,Independently selected from (1H-indole-3-yl) methyl, (1H-imidazol-4-yl) methyl,-(CH2) eCOR3'', aryl, and aryl C1-3 alkyl, the aryl group is Is it optionally substituted with a group selected from hydroxyl, C1-10 alkyl, C1-6 alkoxy, halogen, nitro, and cyano, or (ii) R3a and R3b are both C1-6 alkyl, (iii). ) R3a and R3b are (CH2) f such that they together form a spiro ring, or (iv) R3a is hydrogen and R3b and R2 together contain adjacent N and C atoms. (CH2) n to form a cyclic ring, or (v) R3b to be hydrogen, and R3a and R2 together to form a cyclic ring containing adjacent N and C atoms. (CH2) n, c is 1 to 6, d is 0 to 2, e is 0 to 3, f is 2 to 5, n is 2 to 4, and R3'is , Independently hydrogen or C1-6 alkyl, R3'' is -OR'or -N (R3') 2), or (vi) R3a is H, R3b is H, CH3 , CH2CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, CH2-Indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C (O) NH2, CH2CH2COOH, CH2CH2C (O) NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC (NH) NH2, CH2-imidazol-4-yl, CH2OH, CH (OH) CH3, CH2 ((4'-OH) -Ph), CH2SH, or lower cycloalkyl or (viii) ) R3a is CH3, -CH2CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C (O) NH2, CH2CH2COOH, CH2CH2C (O) NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC (NH) NH2, CH2-imidazol-4-yl, CH2OH, CH (OH) CH3, CH2 ((4'-OH) -Ph), CH2SH, or lower cycloalkyl, where R3b is H And R3'is independently hydrogen or alkyl and includes, but is not limited to, C1-20 alkyl, C1-10 alkyl, or C1-6 alkyl, where R3'' is -OR'. Or -N (R3') 2), (d) R4 is hydrogen, C1-10 alkyl, C1-10 alkyl (optionally substituted with lower alkyl, alkoxy, or halogen), C1-10 haloalkyl, C3-10 cycloalkyl, cycloalkylalkyl, cyclohetero. Alkoxy, aminoacyl, di (lower alkyl) amino-lower alkyl, aryl (phenyl, etc.), heteroaryl (pyridinyl, etc.), substituted aryl, or substituted heteroaryl. (e) R5 is H, lower alkyl, CN, vinyl, O- (lower alkyl), hydroxyl lower alkyl, i.e.-(CH2) pOH, where p is 1-6 and hydroxylmethyl. Contains (CH2OH), CH2F, N3, CH2CN, CH2NH2, CH2NHCH3, CH2N (CH3) 2, alkynes (optionally substituted), or halogens containing F, Cl, Br, or I, provided that When X is OH, the base is cytosine, R6 is H, R5 cannot be N3, when X is OH, R6 is CH3 or CH2F, B is a purine base. , R5 cannot be H, (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN, (g) X is H, OH, F, OMe, Cl, Br, I, NH2, or N3, (h) Y is OH, H, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, vinyl, N3, CN, Cl, Br, F, I, NO2, OC (O) O (C1-4) Alkyl), OC (O) O (C1-4 alkyl), OC (O) O (C2-4 alkynyl), OC (O) O (C2-4 alkenyl), OC1-10 haloalkyl, O (aminoacyl), O (C1-10 Acyl), O (C1-4 Alkyl), O (C2-4 Alkenyl), S (C1-4 Acyl), S (C1-4 Alkyl), S (C2-4 Alkinyl), S (C2 -4 alkenyl), SO (C1-4 acyl), SO (C1-4 alkyl), SO (C2-4 alkynyl), SO (C2-4 alkenyl), SO2 (C1-4 acyl), SO2 (C1-4) Alkyl), SO2 (C2-4 alkynyl), SO2 (C2-4 alkenyl), OS (O) 2 (C1-4 acyl), OS (O) 2 (C1-4 alkyl), OS (O) 2 (C2) -4 alkenyl), NH2, NH (C1-4 alkyl), NH (C2-4 alkenyl), NH (C2-4 alkynyl), NH (C1-4 acyl), N (C1-4 alkyl) 2, or N (C1-18 acyl) 2, alkyl, alkynyl, alkenyl, and vinyl are N3, CN, 1 to 3 halogens (Cl, Br, F, I), NO2, C (O) O (C1- 4 alkyl), C (O) O (C1-4 alkyl), C (O) O (C2-4 alkynyl), C (O) O (C2-4 alkenyl), O (C1-4 acyl), O ( C1-4 alkyl), O (C2-4 alkenyl), S (C1-4 acyl), S (C1-4 alkyl), S (C2-4 alkynyl), S (C2-4 alkenyl), SO (C1-C1- 4-acyl), SO (C1-4 alkyl), SO (C2-4 alkynyl), SO (C2-4 alkenyl), SO2 (C1-4 acyl), SO2 (C1-4 alkyl), SO2 (C2-4 alkynyl) ), SO2 (C2-4 alkenyl), OS (O) 2 (C1-4 acyl), OS (O) 2 (C1-4 alkyl), OS (O) 2 (C2-4 Alkeni), NH2, NH (C1-4 alkyl), NH (C2-4 alkenyl), NH (C2-4 alkynyl), NH (C1-4 acyl), N (C1-4 alkyl) 2, or N (C1) -4 acyl) optionally replaced by 2 (i) R7 and R8 are independently H, F, Cl, Br, I, OH, OR', SH, SR', NH2, NHR', NR'2, lower alkyl, halogenated (F, Cl). , Br, I) Lower alkyl, lower alkenyl of C2-C6, CO2H, CO2R', CONH2, CONHR', CONR'2, where R'is C1-20 alkyl, C1-20 cycloalkyl, C2 -C6 alkenyl, C2-C6 alkynyl.

0033The second aspect of the second embodiment is directed to the compound represented by the formula I-3. During the ceremony (a) R1 is hydrogen, n-alkyl, or aryl, including, but not limited to, phenyl or naphthyl, where phenyl or naphthyl is C1-6 alkyl, C1-6 alkoxy, F, Cl, Arbitrarily substituted with at least one of Br, I, nitro, cyano, C1-6 haloalkyl, (b) R2 is hydrogen or CH3, (c) R3a and R3b are independent, (i) R3a is hydrogen, and R3b and R2 are (CH2) n such that they together form a cyclic ring containing adjacent N and C atoms. Or (v) R3b is hydrogen, R3a and R2 are (CH2) n such that they together form a cyclic ring containing adjacent N and C atoms, and c is 1-6. d is 0 to 2, e is 0 to 3, f is 3 to 5, n is 2 to 4, R3'is independently hydrogen or C1-6 alkyl, R3' 'Is -OR' or -N (R3') 2) or (vi) R3a is H and R3b is H, CH3, CH (CH3) 2, CH2CH (CH3) 2, CH ( CH3) CH2CH3, CH2Ph, CH2-Indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C (O) NH2, CH2CH2COOH, CH2CH2C (O) NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC (NH) NH2, CH2-Imidazole-4-yl, CH2OH, CH (OH) CH3, CH2 ((4'-OH) -Ph), CH2SH, or lower cycloalkyl, or (viii) R3a is CH3, CH (CH3) 2, CH2CH (CH3) 2 , CH (CH3) CH2CH3, CH2Ph, CH2-Indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C (O) NH2, CH2CH2COOH, CH2CH2C (O) NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC (NH) NH2, CH2-Imidazole -Il, CH2OH, CH (OH) CH3, CH2 ((4'-OH) -Ph), or CH2SH, R3b is H, (d) R4 is hydrogen, C1-10 alkyl, C1-10 alkyl (optionally substituted with lower alkyl, alkoxy, or halogen), C1-10 haloalkyl, C3-10 cycloalkyl, cycloalkylalkyl, cyclohetero. Alkoxy, aminoacyl, di (lower alkyl) amino-lower alkyl, aryl (phenyl, etc.), heteroaryl (pyridinyl, etc.), substituted aryl, or substituted heteroaryl. (e) R5 is CH2 (halo) such as H, CN, CH3, vinyl, OCH3, OCH2CH3, CH2OH, CH2F, N3, CH2CN, CH2N3, CH2NH2, CH2NHCH3, CH2N (CH3) 2, F, Cl, Br, Or a halogen containing I, (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN, (g) X is H, OH, F, OMe, halogen, NH2, or N3, (h) Y is OH, H, C1-4 alkyl, vinyl, N3, CN, Cl, Br, F, I, O (C1-6 acyl), O (C1-4 alkyl), NH2, NH (C1) -4 alkyl), NH (C2-4 alkenyl), NH (C2-4 alkynyl), NH (C1-4 acyl), N (C1-4 alkyl) 2, N (C1-18 acyl) 2, Alkyl, alkynyl, alkenyl, and vinyl are N3, CN, 1 to 3 halogens (Cl, Br, F, I), NO2, OC (O) O (C1-4 alkyl), OC (O) O (C1). -4 alkyl), OC (O) O (C2-4 alkynyl), OC (O) O (C2-4 alkenyl), OC1-10 haloalkyl, O (aminoacyl), O (C1-4 acyl), O (C1) -4 alkyl), O (C2-4 alkenyl), S (C1-4 acyl), S (C1-4 alkyl), S (C2-4 alkynyl), S (C2-4 alkenyl), SO (C1-4) Acyl), SO (C1-4 alkyl), SO (C2-4 alkynyl), SO (C2-4 alkenyl), SO2 (C1-4 acyl), SO2 (C1-4 alkyl), SO2 (C2-4 alkynyl) , SO2 (C2-4 alkenyl), OS (O) 2 (C1-4 acyl), OS (O) 2 (C1-4 alkyl), OS (O) 2 (C2-4 alkenyl), NH2, NH (C1 -4 alkyl), NH (C2-4 alkenyl), NH (C2-4 alkynyl), NH (C1-4 acyl), N (C1-4 alkyl) 2, N (C1-4 acyl) 2 optionally substituted Being done (i) R7 and R8 are independently H, F, Cl, Br, I, OH, OR', SH, SR', NH2, NHR', NR'2, lower alkyl, halogenated (F, Cl). , Br, I) Lower alkyl, lower alkenyl of C2-C6, CO2H, CO2R', CONH2, CONHR', CONR'2, where R'is C1-20 alkyl, C1-20 cycloalkyl, C2 -C6 alkenyl, C2-C6 alkynyl.

0034The third aspect of the second embodiment targets the compound represented by the formula I-3. During the ceremony (a) R1 is hydrogen, n-alkyl, or substituted or unsubstituted phenyl, and the substituents of the substituted phenyl are C1-3 alkyl, C1-3 alkoxy, F, Cl, Br, I, nitro, cyano. , And at least one of the C1-3 haloalkyl, (b) R2 is hydrogen, CH3, and R3a or R3b and R2 are (CH2) 3 such that they together form a cyclic ring containing adjacent N and C atoms, C (O) CR3aR3bNHR1. In the equation, n is 2 to 4, and R1, R3a, and R3b are as defined herein. (c) R3a and R3b are independent, (i) R3a is hydrogen, and R3b and R2 together form a cyclic ring containing adjacent N and C atoms at (CH2) n. There is (v) R3b is hydrogen, R3a and R2 are (CH2) n such that together form a cyclic ring containing adjacent N and C atoms, and c is 1 to 6. , D is 0 to 2, e is 0 to 3, f is 3 to 5, n is 2 to 4, and R3'is independently hydrogen or C1-6 alkyl. R3'' is -OR'or -N (R3') 2) or (vi) R3a is H and R3b is H, CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, CH2-Indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C (O) NH2, CH2CH2COOH, CH2CH2C (O) NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC (NH) NH2, CH2-Imidazole-4-yl , CH2OH, CH (OH) CH3, CH2 ((4'-OH) -Ph), CH2SH, or lower cycloalkyl, or (viii) R3a is CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, CH2-Indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C (O) NH2, CH2CH2COOH, CH2CH2C (O) NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC (NH) NH2, CH2-Imidazole 4-Il, CH2OH, CH (OH) CH3, CH2 ((4'-OH) -Ph), CH2SH, or lower cycloalkyl, R3b is H, (d) R4 is hydrogen, CH3, Et, iPr, nPr, nBu, 2-butyl, tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridine-2-yl, N-methyl-azetidine. -3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di (lower alkyl) amino-lower alkyl , (e) R5 includes CH2 (halo) such as H, CN, CH3, OCH3, CH2OH, CH2F, N3, CH2CN, CH2N3, CH2NH2, CH2NHCH3, CH2N (CH3) 2, F, Cl, Br, or I. Halogen, (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN, (g) X is H, OH, F, OCH3, halogen, NH2, or N3, (h) Y is OH, H, CH3, vinyl, N3, CN, Cl, Br, F, I, OC (O) CH3, OCH3, NH2, NHCH3, NH (vinyl), NH (acetyl), NH ( C (O) CH3), N (CH3) 2, N (C (O) CH3) 2, (i) R7 and R8 are independently H, F, Cl, Br, I, OH, OCH3, SH, SCH3, NH2, NHCH3, N (CH3) 2, CH3, CH3-qXq (in the formula, X). Is F, Cl, Br, or I, q is 1 to 3), vinyl, CO2H, CO2CH3, CONH2, CONHCH3, or CON (CH3) 2.

0035The fourth aspect of the second embodiment targets the compound represented by the formula I-3. During the ceremony (a) R1 is hydrogen, n-alkyl, or substituted or unsubstituted phenyl, and substituted or unsubstituted phenyl is CH3, OCH3, F, Cl, Br, I, nitro, cyano, and CH3-qXq ( In the formula, X is F, Cl, Br, or I, and q is 1 to 3). (b) R2 is hydrogen or CH3, (c) R3a is H, R3b is H, CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C (O) NH2, CH2CH2COOH, CH2CH2C (O) NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC (NH) NH2, CH2-imidazol-4-yl, CH2OH, CH (OH) CH3, CH2 ((4'-OH) -Ph) , CH2SH, or lower cycloalkyl, or R3a is CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C (O) NH2, CH2CH2COOH, CH2CH2C (O) NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC (NH) NH2, CH2-imidazol-4-yl, CH2OH, CH (OH) CH3, CH2 ((4'-OH) -Ph) , CH2SH, or lower cycloalkyl, R3b is H, (d) R4 is hydrogen, CH3, Et, iPr, nPr, nBu, 2-butyl, tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridine-2-yl, N-methyl-azetidine. -3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di (lower alkyl) amino-lower alkyl , (e) R5 includes CH2 (halo) such as H, CN, CH3, OCH3, CH2OH, CH2F, N3, CH2CN, CH2N3, CH2NH2, CH2NHCH3, CH2N (CH3) 2, F, Cl, Br, or I. Halogen, (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN, (g) X is H, OH, F, OCH3, NH2, or N3, (h) Y is OH, H, CH3, vinyl, N3, CN, Cl, Br, F, I, OC (O) CH3, OCH3, NH2, NHCH3, NH (vinyl), NH (acetyl), NH ( C (O) CH3), N (CH3) 2, N (C (O) CH3) 2, (i) R7 and R8 are independently H, F, Cl, Br, I, OH, OCH3, SH, SCH3, NH2, NHCH3, N (CH3) 2, CH3, CH3-qXq (in the formula, X is F, Cl, Br, or I, q is 1 to 3), vinyl, CO2H, CO2CH3, CONH2, CONHCH3, or CON (CH3) 2, where R'is C1-20 alkyl, C1-20 cyclo. Alkyl, C2-C6 alkenyl, C2-C6 alkynyl.

0036A fifth aspect of the second embodiment is directed to a compound of formula I-4.<img id="000012" he="76" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />During the ceremony (a) R1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, or substituted or unsubstituted phenyl, and the substituents of the substituted phenyl are CH3, OCH3, F, Cl, Br, I, nitro. , Cyano, and CH3-qXq (in the formula, X is F, Cl, Br, or I, q is 1-3), (b) R2 is hydrogen or CH3, (c) R3a is H, R3b is H, CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C (O) NH2, CH2CH2COOH, CH2CH2C (O) NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC (NH) NH2, CH2-imidazol-4-yl, CH2OH, CH (OH) CH3, CH2 ((4'-OH) -Ph) , CH2SH, or lower cycloalkyl, or R3a is CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C (O) NH2, CH2CH2COOH, CH2CH2C (O) NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC (NH) NH2, CH2-imidazol-4-yl, CH2OH, CH (OH) CH3, CH2 ((4'-OH) -Ph) , CH2SH, or lower cycloalkyl, R3b is H, (d) R4 is hydrogen, CH3, Et, iPr, nPr, nBu, 2-butyl, tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridine-2-yl, N-methyl-azetidine. -3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di (lower alkyl) amino-lower alkyl , (e) R5 is a halogen containing H, CN, CH3, OCH3, CH2OH, CH2F, N3, CH2CN, CH2N3, CH2NH2, CH2NHCH3, CH2N (CH3) 2, F, Cl, Br, or I. (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN, (g) X is H, OH, F, OCH3, Cl, Br, I, NH2, or N3, (h) Y is OH, H, CH3, vinyl, N3, CN, Cl, Br, F, I, OC (O) CH3, OCH3, NH2, NHCH3, NH (vinyl), NH (acetyl), NH ( C (O) CH3), N (CH3) 2, N (C (O) CH3) 2, (i) R7 and R8 are independently H, F, Cl, Br, I, OH, OCH3, SH, SCH3, NH2, NHCH3, N (CH3) 2, CH3, CH3-qXq (in the formula, X). Is F, Cl, Br, or I, q is 1 to 3), vinyl, CO2H, CO2CH3, CONH2, CONHCH3, or CON (CH3) 2, where R'is C1-20 alkyl, C1 -20 Cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl.

0037A sixth aspect of the second embodiment is directed to a compound of formula I-4. During the ceremony (a) R1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl, (b) R2 is hydrogen or CH3, (c) R3a is H, R3b is H, CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, CH2-indole-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C (O) NH2, CH2CH2COOH, CH2CH2C (O) NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC (NH) NH2, CH2-imidazol-4-yl, CH2OH, CH (OH) CH3, CH2 ((4'-OH) -Ph) , CH2SH, or lower cycloalkyl, (d) R4 is hydrogen, CH3, Et, iPr, nPr, nBu, 2-butyl, tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridine-2-yl, N-methyl-azetidine. -3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di (lower alkyl) amino-lower alkyl , (e) R5 is a halogen containing H, CN, CH3, OCH3, CH2OH, CH2F, F, Cl, Br, or I. (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN, (g) X is H, OH, F, OCH3, NH2, or N3, (h) Y is OH, H, CH3, vinyl, NH2, N3, CN, Cl, Br, F, I, OC (O) CH3, OCH3, (i) R7 and R8 are independently H, F, Cl, Br, I, OH, OCH3, SH, SCH3, NH2, NHCH3, N (CH3) 2, CH3, CH3-qXq (in the formula, X). Is F, Cl, Br, or I, q is 1 to 3), vinyl, CO2H, CO2CH3, CONH2, CONHCH3, or CON (CH3) 2, where R'is C1-20 alkyl, C1 -20 Cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl.

0038A seventh aspect of the second embodiment is directed to a compound of formula I-4. During the ceremony (a) R1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl, (b) R2 is hydrogen or CH3, (c) R3a is H, R3b is H, CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, or lower cycloalkyl. (d) R4 is hydrogen, CH3, Et, iPr, nPr, nBu, 2-butyl, tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridine-2-yl, N-methyl-azetidine. -3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di (lower alkyl) amino-lower alkyl , (e) R5 is H, OMe, CN, CH2F, F, Cl, Br, or I, (f) R6 is H, CH3, CH2F, CHF2, CF3, or F, (g) X is H, OH, F, OCH3, F, Cl, Br, I, NH2, or N3, (h) Y is H, OH, CH3, F, Cl, Br, I, NH2 or N3, OCH3, or OC (O) CH3. (i) R7 and R8 are independently H, F, Br, SCH3, CH3, CH3-qXq (in the formula, X is F, Cl, Br, or I, q is 1 to 3). , Vinyl, CO2CH3, CONH2, CONHCH3, or CON (CH3) 2,

0039The eighth aspect of the second embodiment is directed to the compound represented by the formula I-4. During the ceremony (a) R1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl, (b) R2 is hydrogen, (c) R3a is H, R3b is H, CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, or lower cycloalkyl. (d) R4 is hydrogen, CH3, Et, iPr, nPr, nBu, 2-butyl, tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridine-2-yl, N-methyl-azetidine. -3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di (lower alkyl) amino-lower alkyl , (e) R5 is H, (f) R6 is H, CH3, CH2F, CHF2, CF3, or F, (g) X is H, OH, OCH3, F, NH2, or N3, (h) Y is OH, NH2, OCH3, or OC (O) CH3, (i) R7 and R8 are independently H, F, Br, SCH3, CH3, CH3-qXq (in the formula, X is F, Cl, Br, or I, q is 1 to 3). , Vinyl, CO2CH3, CONH2, CONHCH3, or CON (CH3) 2.

0040A ninth aspect of the second embodiment is directed to a compound of formula I-4. During the ceremony (a) R1 is hydrogen, methyl, phenyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl, (b) R2 is hydrogen, (c) R3a is H, R3b is H, CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, or lower cycloalkyl. (d) R4 is hydrogen, CH3, Et, iPr, nPr, nBu, 2-butyl, tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridine-2-yl, N-methyl-azetidine. -3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di (lower alkyl) amino-lower alkyl , (e) R5 is H, (f) R6 is H, CH3, CH2F, CHF2, CF3, or F, (g) X is H, OH, OCH3, F, or N3, (h) Y is OH, OCH3, or OC (O) CH3, (i) R7 and R8 are independently H, F, Br, SCH3, CH3, CH3-qXq (in the formula, X is F, Cl, Br, or I, q is 1 to 3). , Vinyl, CO2CH3, CONH2, CONHCH3, or CON (CH3) 2.

0041The third embodiment of the present invention targets a compound represented by the formula I, in which the base has a structure represented by the above formula c, and has a structure represented by the above formula c, R1, R2, R3a, R3b, R4, R5, R6, X, Y, Z, R10, R11, and R12 are defined in the section of the outline of the invention above, provided that R11 is not H. The first aspect of the third embodiment is directed to a compound represented by formula I-5.<img id="000013" he="62" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />During the ceremony (a) R1 is hydrogen, n-alkyl, branched alkyl, cycloalkyl, or aryl, including, but not limited to, phenyl or naphthyl, where phenyl or naphthyl is C1-6 alkyl, C2-6 alkoxy, C2-6 alkynyl, C1-6 alkoxy, F, Cl, Br, I, nitro, cyano, C1-6 haloalkyl, -N (R1) 2, C1-6 acylamino, -NHSO2 C1-6 alkyl, -SO2N (R1' ) 2, COR1'', and -SO2C1-6 alkyl optionally substituted (R1'is independently hydrogen, or alkyl, C1-20 alkyl, C1-10 alkyl , Or including, but not limited to, C1-6 alkyl, where R1'' is -OR'or -N (R1') 2), (b) R2 is hydrogen or CH3, (c) R3a and R3b are (i) hydrogen, C1-10 alkyl, cycloalkyl,-(CH2) c (NR3') 2, C1-6 hydroxyalkyl, -CH2SH,-(CH2) 2S (O) dMe. ,-(CH2) 3NHC (= NH) NH2, (1H-indole-3-yl) methyl, (1H-imidazol-4-yl) methyl,-(CH2) eCOR3'', aryl, and aryl C1-3 alkyl The aryl group is optionally substituted with a group selected from hydroxyl, C1-10 alkyl, C1-6 alkoxy, halogen, nitro, and cyano, or (ii) R3a and R3b , Both are C1-6 alkyl, (iii) R3a and R3b are (CH2) f such that they together form a spiro ring, (iv) R3a is hydrogen, and R3b and R2 are. , Together they are (CH2) n such as to form a cyclic ring containing adjacent N and C atoms, or (v) R3b is hydrogen and R3a and R2 together are adjacent N and (CH2) n that forms a cyclic ring containing C atoms, c is 1 to 6, d is 0 to 2, e is 0 to 3, and f is 2 to 5. , N are 2 to 4, R3'is independently hydrogen or C1-6 alkyl, R3'' is -OR' or -N (R3') 2), or (vi) R3a Is H and R3b is H, CH3, CH2CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C ( O) NH2, CH2CH2COOH, CH2CH2C (O) NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC (NH) NH2, CH2-imidazol-4-yl, CH2OH, CH (OH) CH3, CH2 ((4'-OH) -Ph), CH2SH , Or from lower cycloalkyl, or (viii) R3a, CH3, -CH2CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, CH2-Indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C (O) NH2, CH2CH2COOH, CH2CH2C (O) NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC (NH) NH CH2-imidazol-4-yl, CH2OH, CH (OH) CH3, CH2 ((4'-OH) -Ph), CH2SH, or lower cycloalkyl, R3b is H, R3'is independent Hydrogen or alkyl, including, but not limited to, C1-20 alkyl, C1-10 alkyl, or C1-6 alkyl, where R3'' is -OR'or -N (R3') 2). And (d) R4 is hydrogen, C1-10 alkyl, C1-10 alkyl (optionally substituted with lower alkyl, alkoxy, or halogen), C1-10 haloalkyl, C3-10 cycloalkyl, cycloalkylalkyl, cyclohetero. Alkoxy, aminoacyl, di (lower alkyl) amino-lower alkyl, aryl (phenyl, etc.), heteroaryl (pyridinyl, etc.), substituted aryl, or substituted heteroaryl. (e) R5 is H, lower alkyl, CN, vinyl, O- (lower alkyl), hydroxyl lower alkyl, i.e.-(CH2) pOH, where p is 1-6 and hydroxylmethyl. Contains (CH2OH), CH2F, N3, CH2CN, CH2NH2, CH2NHCH3, CH2N (CH3) 2, alkynes (optionally substituted), or halogens containing F, Cl, Br, or I, provided that When X is OH, the base is cytosine, R6 is H, R5 cannot be N3, when X is OH, R6 is CH3 or CH2F, B is a purine base. , R5 cannot be H, (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN, (g) X is H, OH, F, OMe, halogen, NH2, or N3, (h) Y is OH, H, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, vinyl, N3, CN, Cl, Br, F, I, NO2, OC (O) O (C1-4) Alkyl), OC (O) O (C1-4 alkyl), OC (O) O (C2-4 alkynyl), OC (O) O (C2-4 alkenyl), OC1-10 haloalkyl, O (aminoacyl), O (C1-10 Acyl), O (C1-4 Alkyl), O (C2-4 Alkenyl), S (C1-4 Acyl), S (C1-4 Alkyl), S (C2-4 Alkinyl), S (C2 -4 alkenyl), SO (C1-4 acyl), SO (C1-4 alkyl), SO (C2-4 alkynyl), SO (C2-4 alkenyl), SO2 (C1-4 acyl), SO2 (C1-4) Alkyl), SO2 (C2-4 alkynyl), SO2 (C2-4 alkenyl), OS (O) 2 (C1-4 acyl), OS (O) 2 (C1-4 alkyl), OS (O) 2 (C2) -4 alkenyl), NH2, NH (C1-4 alkyl), NH (C2-4 alkenyl), NH (C2-4 alkynyl), NH (C1-4 acyl), N (C1-4 alkyl) 2, N ( C1-18 acyl) 2, alkyl, alkynyl, alkenyl, and vinyl are N3, CN, 1 to 3 halogens (Cl, Br, F, I), NO2, C (O) O (C1-4). Alkyl), C (O) O (C1-4 alkyl), C (O) O (C2-4 alkynyl), C (O) O (C2-4 alkenyl), O (C1-4 acyl), O (C1) -4 alkyl), O (C2-4 alkenyl), S (C1-4 acyl), S (C1-4 alkyl), S (C2-4 alkynyl), S (C2-4 alkenyl), SO (C1-4) Acyl), SO (C1-4 alkyl), SO (C2-4 alkynyl), SO (C2-4 alkenyl), SO2 (C1-4 acyl), SO2 (C1-4 alkyl), SO2 (C2-4 alkynyl) , SO2 (C2-4 alkenyl), OS (O) 2 (C1-4 acyl), OS (O) 2 (C1-4 alkyl), OS (O) 2 (C2-4 alkenyl),NH2, NH (C1-4 alkyl), NH (C2-4 alkenyl), NH (C2-4 alkynyl), NH (C1-4 acyl), N (C1-4 alkyl) 2, N (C1-4 acyl) Arbitrarily replaced by 2 (i) R10 and R11 are independently H, F, Cl, Br, I, OH, OR', SH, SR', NH2, NHR', NR'2, C1-C6 lower alkyl, C1- Halogenation of C6 (F, Cl, Br, I) lower alkyl, lower alkenyl of C2-C6, halogenation of C2-C6 (F, Cl, Br, I) lower alkenyl, lower alkynyl of C2-C6<img id="000014" he="6" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />C2-C6 Halogenation (F, Cl, Br, I) Lower Alkyne, C1-C6 Lower Alkoxy, C1-C6 Halogenation (F, Cl, Br, I) Lower Alkoxy, CO2H, CO2R', CONH2, CONHR', CONR'2, CH = CHCO2H, or CH = CHCO2R', provided that if R10 is OH, then R11 is not NH2. R'is optionally substituted alkyl, including, but not limited to, optionally substituted C1-20 alkyl, optionally substituted C1-10 alkyl, optionally substituted lower alkyl. , Arbitrarily substituted cycloalkyl, optionally substituted alkynyl of C2-C6, optionally substituted lower alkenyl of C2-C6, or optionally substituted acyl, C (O) alkyl, C Includes, but is not limited to, (O) (C1-20 alkyl), C (O) (C1-10 alkyl), or C (O) (lower alkyl), or, as an alternative, NR'2 , Each R'contains at least one C atom that is linked to form a heterocycle containing at least two carbon atoms. (j) Z is N or CR12 R12 is H, halogen (including F, Cl, Br, I), OH, OR', SH, SR', NH2, NHR', NR'2, NO2, lower alkyl of C1-C6, C1-C6. Halogenated (F, Cl, Br, I) lower alkyl, C2-C6 lower alkenyl, C2-C6 halogenated (F, Cl, Br, I) lower alkenyl, C2-C lower alkynyl 6, C2-C6 Halogenation (F, Cl, Br, I) lower alkynyl, C1-C6 lower alkoxy, C1-C6 halogenation (F, Cl, Br, I) lower alkoxy, CO2H, CO2R', CONH2, CONHR', CONR'2, CH = CHCO2H, or CH = CHCO2R'.

0042The second aspect of the third embodiment is directed to the compound represented by the formula I-5. During the ceremony (a) R1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl, (b) R2 is hydrogen or CH3, (c) R3a is H, R3b is H, CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, CH2-indole-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C (O) NH2, CH2CH2COOH, CH2CH2C (O) NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC (NH) NH2, CH2-imidazol-4-yl, CH2OH, CH (OH) CH3, CH2 ((4'-OH) -Ph) , CH2SH, or lower cycloalkyl, (d) R4 is hydrogen, CH3, Et, iPr, nPr, nBu, 2-butyl, tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridine-2-yl, N-methyl-azetidine. -3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, lower haloalkyl, or di (lower alkyl) amino-lower alkyl, (e) R5 is a halogen containing H, CN, CH3, OCH3, CH2OH, CH2F, F, Cl, Br, or I, except that when X is OH, R6 is CH3 or CH2F. R5 cannot be H, provided (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN, (g) X is H, OH, F, OCH3, Cl, Br, I, NH2, or N3, (h) Y is OH, H, CH3, vinyl, NH2, N3, CN, Cl, Br, F, I, OC (O) CH3, OCH3, (i) R10 and R11 are independently H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, CONHR', CONR'2, CH = CHCO2H, Or CH = CHCO2R', provided that when R10 is OH, R11 is not NH2. R'is a lower alkyl, lower cycloalkyl, or C (O) (lower alkyl), or, in the case of NR'2, each R'is concatenated and contains at least two carbon atoms. Contains at least one C atom forming a heterocycle (j) Z is N or CR12 R12 is H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of C1-C6, CO2R', CONH2, CONHR', CONR'2 , CH = CHCO2H, or CH = CHCO2R'.

0043The third aspect of the third embodiment is directed to the compound represented by the formula I-5. During the ceremony (a) R1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl, (b) R2 is hydrogen or CH3, (c) R3a is H, R3b is H, CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, or lower cycloalkyl. (d) R4 is hydrogen, CH3, Et, iPr, nPr, nBu, 2-butyl, tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridine-2-yl, N-methyl-azetidine. -3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di (lower alkyl) amino-lower alkyl , (e) R5 is H, CN, CH2F, F, Cl, Br, or I, except that X is OH, R6 is CH3 or CH2F, and R5 cannot be H. As a condition (f) R6 is H, CH3, CH2F, CHF2, CF3, or F, (g) X is H, OH, F, OCH3, F, Cl, Br, I, NH2, or N3, (h) Y is H, OH, CH3, F, Cl, Br, I, NH2 or N3, OCH3, or OC (O) CH3. (i) R10 and R11 are independently H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, CONHR', CONR'2, CH = CHCO2H, Or CH = CHCO2R', provided that when R10 is OH, R11 is not NH2. R'is a lower alkyl, lower cycloalkyl, or C (O) (lower alkyl), or, in the case of NR'2, each R'is concatenated and contains at least two carbon atoms. Contains at least one C atom forming a heterocycle (j) Z is N or CR12 R12 is H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of C1-C6, CO2R', CONH2, CONHR', CONR'2 , CH = CHCO2H, or CH = CHCO2R'.

0044The fourth aspect of the third embodiment targets the compound represented by the formula I-5. During the ceremony (a) R1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl, (b) R2 is hydrogen, (c) R3a is H, R3b is H, CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, or lower cycloalkyl. (d) R4 is hydrogen, CH3, Et, iPr, nPr, nBu, 2-butyl, tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridine-2-yl, N-methyl-azetidine. -3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di (lower alkyl) amino-lower alkyl , (e) R5 is H, provided that when X is OH, R6 is CH3 or CH2F and R5 cannot be H. (f) R6 is H, CH3, CH2F, CHF2, CF3, or F, (g) X is H, OH, OCH3, F, NH2, or N3, (h) Y is OH, NH2, OCH3, or OC (O) CH3, (i) R10 and R11 are independently H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, CONHR', CONR'2, CH = CHCO2H, Or CH = CHCO2R', provided that when R10 is OH, R11 is not NH2. R'is a lower alkyl, lower cycloalkyl, or C (O) (lower alkyl), or, in the case of NR'2, each R'is concatenated and contains at least two carbon atoms. Contains at least one C atom forming a heterocycle (j) Z is N or CR12 R12 is H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of C1-C6, CO2R', CONH2, CONHR', CONR'2 , CH = CHCO2H, or CH = CHCO2R'.

0045A fifth aspect of the third embodiment is directed to a compound of formula I-5. During the ceremony (a) R1 is hydrogen, methyl, phenyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl, (b) R2 is hydrogen, (c) R3a is H, R3b is H, CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, or lower cycloalkyl. (d) R4 is hydrogen, CH3, Et, iPr, nPr, nBu, 2-butyl, tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridine-2-yl, N-methyl-azetidine. -3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di (lower alkyl) amino-lower alkyl , (e) R5 is H, provided that when X is OH, R6 is CH3 or CH2F and R5 cannot be H. (f) R6 is H, CH3, CH2F, CHF2, CF3, or F, (g) X is H, OH, OCH3, F, NH2, or N3, (h) Y is OH, NH2, OCH3, or OC (O) CH3, (i) R10 and R11 are independently H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, CONHR', CONR'2, CH = CHCO2H, Or CH = CHCO2R', provided that when R10 is OH, R11 is not NH2. R'is a lower alkyl, lower cycloalkyl, or C (O) (lower alkyl), or, in the case of NR'2, each R'is concatenated and contains at least two carbon atoms. Contains at least one C atom forming a heterocycle (j) Z is N or CR12 R12 is H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of C1-C6, CO2R', CONH2, CONHR', CONR'2 , CH = CHCO2H, or CH = CHCO2R'.

0046The sixth aspect of the third embodiment is directed to the compound represented by the formula I-5. During the ceremony (a) R1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl, (b) R2 is hydrogen or CH3, (c) R3a is H, R3b is H, CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, CH2-indole-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C (O) NH2, CH2CH2COOH, CH2CH2C (O) NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC (NH) NH2, CH2-imidazol-4-yl, CH2OH, CH (OH) CH3, CH2 ((4'-OH) -Ph) , CH2SH, or lower cycloalkyl, (d) R4 is hydrogen, CH3, Et, iPr, nPr, nBu, 2-butyl, tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridine-2-yl, N-methyl-azetidine. -3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di (lower alkyl) amino-lower alkyl , (e) R5 is a halogen containing H, CN, CH3, OCH3, CH2OH, CH2F, F, Cl, Br, or I, except that when X is OH, R6 is CH3 or CH2F. R5 cannot be H, provided (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN, (g) X is H, OH, F, OCH3, Cl, Br, I, NH2, or N3, (h) Y is OH, H, CH3, vinyl, NH2, N3, CN, Cl, Br, F, I, OC (O) CH3, OCH3, (i) R10 is NH2, R11 is H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, CONHR', CONR'2, CH = CHCO2H , Or CH = CHCO2R', R'is a lower alkyl, lower cycloalkyl, or C (O) (lower alkyl), or, in the case of NR'2, each R'is concatenated and contains at least two carbon atoms. Contains at least one C atom forming a heterocycle (j) Z is N or CR12 R12 is H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of C1-C6, CO2R', CONH2, CONHR', CONR'2 , CH = CHCO2H, or CH = CHCO2R'.

0047A seventh aspect of the third embodiment is directed to a compound of formula I-5. During the ceremony (a) R1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl, (b) R2 is hydrogen or CH3, (c) R3a is H, R3b is H, CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, or lower cycloalkyl. (d) R4 is hydrogen, CH3, Et, iPr, nPr, nBu, 2-butyl, tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridine-2-yl, N-methyl-azetidine. -3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di (lower alkyl) amino-lower alkyl , (e) R5 is H, CN, CH2F, F, Cl, Br, or I, except that X is OH, R6 is CH3 or CH2F, and R5 cannot be H. As a condition (f) R6 is H, CH3, CH2F, CHF2, CF3, or F, (g) X is H, OH, F, OCH3, F, Cl, Br, I, NH2, or N3, (h) Y is H, OH, CH3, F, Cl, Br, I, NH2 or N3, OCH3, or OC (O) CH3. (i) R10 is NH2, R11 is H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, CONHR', CONR'2, CH = CHCO2H , Or CH = CHCO2R', R'is a lower alkyl, lower cycloalkyl, or C (O) (lower alkyl), or, in the case of NR'2, each R'is concatenated and contains at least two carbon atoms. Contains at least one C atom forming a heterocycle (j) Z is N or CR12 R12 is H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of C1-C6, CO2R', CONH2, CONHR', CONR'2 , CH = CHCO2H, or CH = CHCO2R'.

0048The eighth aspect of the third embodiment is directed to the compound represented by the formula I-5. During the ceremony (a) R1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl, (b) R2 is hydrogen, (c) R3a is H, R3b is H, CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, or lower cycloalkyl. (d) R4 is hydrogen, CH3, Et, iPr, nPr, nBu, 2-butyl, tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridine-2-yl, N-methyl-azetidine. -3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidine-4-yl, lower haloalkyl, (e) R5 is H, provided that when X is OH, R6 is CH3 or CH2F and R5 cannot be H. (f) R6 is H, CH3, CH2F, CHF2, CF3, or F, (g) X is H, OH, OCH3, F, NH2, or N3, (h) Y is OH, NH2, OCH3, or OC (O) CH3, (i) R10 is NH2, R11 is H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, CONHR', CONR'2, CH = CHCO2H , Or CH = CHCO2R', R'is a lower alkyl, lower cycloalkyl, or C (O) (lower alkyl), or, in the case of NR'2, each R'is concatenated and contains at least two carbon atoms. Contains at least one C atom forming a heterocycle (j) Z is N or CR12 R12 is H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of C1-C6, CO2R', CONH2, CONHR', CONR'2 , CH = CHCO2H, or CH = CHCO2R'.

0049A ninth aspect of the third embodiment is directed to a compound of formula I-5. During the ceremony (a) R1 is hydrogen, methyl, phenyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl, (b) R2 is hydrogen, (c) R3a is H, R3b is H, CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, or lower cycloalkyl. (d) R4 is hydrogen, CH3, Et, iPr, nPr, nBu, 2-butyl, tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridine-2-yl, N-methyl-azetidine. -3-yl, N-methyl-pyrrolidin-3-yl, or N-methyl-pyrrolidin-4-yl, lower haloalkyl, or di (lower alkyl) amino-lower alkyl, (e) R5 is H, provided that when X is OH, R6 is CH3 or CH2F and R5 cannot be H. (f) R6 is H, CH3, CH2F, CHF2, CF3, or F, (g) X is H, OH, OCH3, F, NH2, or N3, (h) Y is OH, NH2, OCH3, or OC (O) CH3, (i) R10 is NH2, R11 is H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, CONHR', CONR'2, CH = CHCO2H , Or CH = CHCO2R', R'is a lower alkyl, lower cycloalkyl, or C (O) (lower alkyl), or, in the case of NR'2, each R'is concatenated and contains at least two carbon atoms. Contains at least one C atom forming a heterocycle (j) Z is N or CR12 R12 is H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of C1-C6, CO2R', CONH2, CONHR', CONR'2 , CH = CHCO2H, or CH = CHCO2R'.

0050The tenth aspect of the third embodiment is directed to the compound represented by the formula I-6 .<img id="000015" he="62" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />During the ceremony (a) R1 is hydrogen, n-alkyl, branched alkyl, cycloalkyl, or aryl, including, but not limited to, phenyl or naphthyl, where phenyl or naphthyl is C1-6 alkyl, C2-6 alkoxy, C2-6 alkynyl, C1-6 alkoxy, F, Cl, Br, I, nitro, cyano, C1-6 haloalkyl, -N (R1) 2, C1-6 acylamino, -NHSO2 C1-6 alkyl, -SO2N (R1' ) 2, COR1'', and -SO2C1-6 alkyl optionally substituted (R1'is independently hydrogen, or alkyl, C1-20 alkyl, C1-10 alkyl , Or including, but not limited to, C1-6 alkyl, where R1'' is -OR'or -N (R1') 2), (b) R2 is hydrogen or CH3, (c) R3a and R3b are (i) hydrogen, C1-10 alkyl, cycloalkyl,-(CH2) c (NR3') 2, C1-6 hydroxyalkyl, -CH2SH,-(CH2) 2S (O) dMe. ,-(CH2) 3NHC (= NH) NH2,Independently selected from (1H-indole-3-yl) methyl, (1H-imidazol-4-yl) methyl,-(CH2) eCOR3'', aryl, and aryl C1-3 alkyl, the aryl group is Is it optionally substituted with a group selected from hydroxyl, C1-10 alkyl, C1-6 alkoxy, halogen, nitro, and cyano, or (ii) R3a and R3b are both C1-6 alkyl, (iii). ) R3a and R3b are (CH2) f such that they together form a spiro ring, or (iv) R3a is hydrogen and R3b and R2 together contain adjacent N and C atoms. (CH2) n to form a cyclic ring, or (v) R3b to be hydrogen, and R3a and R2 together to form a cyclic ring containing adjacent N and C atoms. (CH2) n, c is 1 to 6, d is 0 to 2, e is 0 to 3, f is 2 to 5, n is 2 to 4, and R3'is , Independently hydrogen or C1-6 alkyl, R3'' is -OR'or -N (R3') 2), or (vi) R3a is H, R3b is H, CH3 , CH2CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, CH2-Indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C (O) NH2, CH2CH2COOH, CH2CH2C (O) NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC (NH) NH2, CH2-imidazol-4-yl, CH2OH, CH (OH) CH3, CH2 ((4'-OH) -Ph), CH2SH, or lower cycloalkyl or (viii) ) R3a is CH3, -CH2CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C (O) NH2, CH2CH2COOH, CH2CH2C (O) NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC (NH) NH2, CH2-imidazol-4-yl, CH2OH, CH (OH) CH3, CH2 ((4'-OH) -Ph), CH2SH, or lower cycloalkyl, where R3b is H And R3'is independently hydrogen or alkyl and includes, but is not limited to, C1-20 alkyl, C1-10 alkyl, or C1-6 alkyl, where R3'' is -OR'. Or -N (R3') 2), (d) R4 is hydrogen, C1-10 alkyl, C1-10 alkyl (optionally substituted with lower alkyl, alkoxy, or halogen), C1-10 haloalkyl, C3-10 cycloalkyl, cycloalkylalkyl, cyclohetero. Alkoxy, aminoacyl, di (lower alkyl) amino-lower alkyl, aryl (phenyl, etc.), heteroaryl (pyridinyl, etc.), substituted aryl, or substituted heteroaryl. (e) R5 is H, lower alkyl, CN, vinyl, O- (lower alkyl), hydroxyl lower alkyl, i.e.-(CH2) pOH, where p is 1-6 and hydroxylmethyl. Contains (CH2OH), CH2F, N3, CH2CN, CH2NH2, CH2NHCH3, CH2N (CH3) 2, alkynes (optionally substituted), or halogens containing F, Cl, Br, or I, provided that When X is OH, the base is cytosine, R6 is H, R5 cannot be N3, when X is OH, R6 is CH3 or CH2F, B is a purine base. , R5 cannot be H, (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN, (g) X is H, OH, F, OMe, Cl, Br, I, NH2, or N3, (h) Y is OH, H, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, vinyl, N3, CN, Cl, Br, F, I, NO2, OC (O) O (C1-4) Alkyl), OC (O) O (C1-4 alkyl), OC (O) O (C2-4 alkynyl), OC (O) O (C2-4 alkenyl), OC1-10 haloalkyl, O (aminoacyl), O (C1-10 Acyl), O (C1-4 Alkyl), O (C2-4 Alkenyl), S (C1-4 Acyl), S (C1-4 Alkyl), S (C2-4 Alkinyl), S (C2 -4 alkenyl), SO (C1-4 acyl), SO (C1-4 alkyl), SO (C2-4 alkynyl), SO (C2-4 alkenyl), SO2 (C1-4 acyl), SO2 (C1-4) Alkyl), SO2 (C2-4 alkynyl), SO2 (C2-4 alkenyl), OS (O) 2 (C1-4 acyl), OS (O) 2 (C1-4 alkyl), OS (O) 2 (C2) -4 alkenyl), NH2, NH (C1-4 alkyl), NH (C2-4 alkenyl), NH (C2-4 alkynyl), NH (C1-4 acyl), N (C1-4 alkyl) 2, N ( C1-18 acyl) 2, alkyl, alkynyl, alkenyl, and vinyl are N3, CN, 1 to 3 halogens (Cl, Br, F, I), NO2, C (O) O (C1-4). Alkyl), C (O) O (C1-4 alkyl), C (O) O (C2-4 alkynyl), C (O) O (C2-4 alkenyl), O (C1-4 acyl), O (C1) -4 alkyl), O (C2-4 alkenyl), S (C1-4 acyl), S (C1-4 alkyl), S (C2-4 alkynyl), S (C2-4 alkenyl), SO (C1-4) Acyl), SO (C1-4 alkyl), SO (C2-4 alkynyl), SO (C2-4 alkenyl), SO2 (C1-4 acyl), SO2 (C1-4 alkyl), SO2 (C2-4 alkynyl) , SO2 (C2-4 alkenyl), OS (O) 2 (C1-4 acyl), OS (O) 2 (C1-4 alkyl), OS (O) 2 (C2-4 alkenyl),NH2, NH (C1-4 alkyl), NH (C2-4 alkenyl), NH (C2-4 alkynyl), NH (C1-4 acyl), N (C1-4 alkyl) 2, N (C1-4 acyl) Arbitrarily replaced by 2 (i) R10 and R11 are independently H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, CONHR', CONR'2, CH = CHCO2H, Or CH = CHCO2R', provided that when R10 is OH, R11 is not NH2. R'is a lower alkyl, lower cycloalkyl, or C (O) (lower alkyl), or, in the case of NR'2, each R'is concatenated and contains at least two carbon atoms. Contains at least one C atom forming a heterocycle (j) Z is N or CR12 R12 is H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of C1-C6, CO2R', CONH2, CONHR', CONR'2 , CH = CHCO2H, or CH = CHCO2R'.

0051The eleventh aspect of the third embodiment targets the compound represented by the formula I-6. During the ceremony (a) R1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl, (b) R2 is hydrogen or CH3, (c) R3a is H, R3b is H, CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, CH2-indole-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C (O) NH2, CH2CH2COOH, CH2CH2C (O) NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC (NH) NH2, CH2-imidazol-4-yl, CH2OH, CH (OH) CH3, CH2 ((4'-OH) -Ph) , CH2SH, or lower cycloalkyl, (d) R4 is hydrogen, CH3, Et, iPr, nPr, nBu, 2-butyl, tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridine-2-yl, N-methyl-azetidine. -3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di (lower alkyl) amino-lower alkyl , (e) R5 is a halogen containing H, CN, CH3, OCH3, CH2OH, CH2F, F, Cl, Br, or I, except that when X is OH, R6 is CH3 or CH2F. R5 cannot be H, provided (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN, (g) X is H, OH, F, OCH3, Cl, Br, I, NH2, or N3, (h) Y is OH, H, CH3, vinyl, NH2, N3, CN, Cl, Br, F, I, OC (O) CH3, OCH3, (i) R10 and R11 are independently H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, CONHR', CONR'2, CH = CHCO2H, Or CH = CHCO2R', provided that when R10 is OH, R11 is not NH2. R'is a lower alkyl, lower cycloalkyl, or C (O) (lower alkyl), or, in the case of NR'2, each R'is concatenated and contains at least two carbon atoms. Contains at least one C atom forming a heterocycle (j) Z is N or CR12 R12 is H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of C1-C6, CO2R', CONH2, CONHR', CONR'2 , CH = CHCO2H, or CH = CHCO2R'.

0052The twelfth aspect of the third embodiment targets the compound represented by the formula I-6. During the ceremony (a) R1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl, (b) R2 is hydrogen or CH3, (c) R3a is H, R3b is H, CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, or lower cycloalkyl. (d) R4 is hydrogen, CH3, Et, iPr, nPr, nBu, 2-butyl, tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridine-2-yl, N-methyl-azetidine. -3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di (lower alkyl) amino-lower alkyl , (e) R5 is H, CN, CH2F, F, Cl, Br, or I, except that when X is OH, R6 is CH3 or CH2F and R5 cannot be H. As a condition, (f) R6 is H, CH3, CH2F, CHF2, CF3, or F, (g) X is H, OH, F, OCH3, F, Cl, Br, I, NH2, or N3, (h) Y is H, OH, CH3, F, Cl, Br, I, NH2 or N3, OCH3, or OC (O) CH3. (i) R10 and R11 are independently H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, CONHR', CONR'2, CH = CHCO2H, Or CH = CHCO2R', provided that when R10 is OH, R11 is not NH2. R'is a lower alkyl, lower cycloalkyl, or C (O) (lower alkyl), or, in the case of NR'2, each R'is concatenated and contains at least two carbon atoms. Contains at least one C atom forming a heterocycle (j) Z is N or CR12 R12 is H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of C1-C6, CO2R', CONH2, CONHR', CONR'2 , CH = CHCO2H, or CH = CHCO2R'.

0053The thirteenth aspect of the third embodiment targets the compound represented by the formula I-6. During the ceremony (a) R1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl, (b) R2 is hydrogen, (c) R3a is H, R3b is H, CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, or lower cycloalkyl. (d) R4 is hydrogen, CH3, Et, iPr, nPr, nBu, 2-butyl, tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridine-2-yl, N-methyl-azetidine. -3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di (lower alkyl) amino-lower alkyl , (e) R5 is H, provided that when X is OH, R6 is CH3 or CH2F and R5 cannot be H. (f) R6 is H, CH3, CH2F, CHF2, CF3, or F, (g) X is H, OH, OCH3, F, NH2, or N3, (h) Y is OH, NH2, OCH3, or OC (O) CH3, (i) R10 and R11 are independently H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, CONHR', CONR'2, CH = CHCO2H, Or CH = CHCO2R', provided that when R10 is OH, R11 is not NH2. R'is a lower alkyl, lower cycloalkyl, or C (O) (lower alkyl), or, in the case of NR'2, each R'is concatenated and contains at least two carbon atoms. Contains at least one C atom forming a heterocycle (j) Z is N or CR12 R12 is H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of C1-C6, CO2R', CONH2, CONHR', CONR'2 , CH = CHCO2H, or CH = CHCO2R'.

0054The fourteenth aspect of the third embodiment is directed to the compound represented by the formula I-6. During the ceremony (a) R1 is hydrogen, methyl, phenyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl, (b) R2 is hydrogen, (c) R3a is H, R3b is H, CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, or lower cycloalkyl. (d) R4 is hydrogen, CH3, Et, iPr, nPr, nBu, 2-butyl, tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridine-2-yl, N-methyl-azetidine. -3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di (lower alkyl) amino-lower alkyl , (e) R5 is H, provided that when X is OH, R6 is CH3 or CH2F and R5 cannot be H. (f) R6 is H, CH3, CH2F, CHF2, CF3, or F, (g) X is H, OH, OCH3, F, NH2, or N3, (h) Y is OH, NH2, OCH3, or OC (O) CH3, (i) R10 and R11 are independently H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, CONHR', CONR'2, CH = CHCO2H, Or CH = CHCO2R', provided that when R10 is OH, R11 is not NH2. R'is a lower alkyl, lower cycloalkyl, or C (O) (lower alkyl), or, in the case of NR'2, each R'is concatenated and contains at least two carbon atoms. Contains at least one C atom forming a heterocycle (j) Z is N or CR12 R12 is H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of C1-C6, CO2R', CONH2, CONHR', CONR'2 , CH = CHCO2H, or CH = CHCO2R'.

0055A fifteenth aspect of the third embodiment is directed to a compound represented by formula I-6. During the ceremony (a) R1 is hydrogen, n-alkyl, branched alkyl, cycloalkyl, or aryl, including, but not limited to, phenyl or naphthyl, where phenyl or naphthyl is C1-6 alkyl, C2-6 alkoxy, C2-6 alkynyl, C1-6 alkoxy, F, Cl, Br, I, nitro, cyano, C1-6 haloalkyl, -N (R1) 2, C1-6 acylamino, -NHSO2 C1-6 alkyl, -SO2N (R1' ) 2, COR1'', and -SO2C1-6 alkyl optionally substituted (R1'is independently hydrogen, or alkyl, C1-20 alkyl, C1-10 alkyl , Or including, but not limited to, C1-6 alkyl, where R1'' is -OR'or -N (R1') 2), (b) R2 is hydrogen or CH3, (c) R3a and R3b are (i) hydrogen, C1-10 alkyl, cycloalkyl,-(CH2) c (NR3') 2, C1-6 hydroxyalkyl, -CH2SH,-(CH2) 2S (O) dMe. ,-(CH2) 3NHC (= NH) NH2,Independently selected from (1H-indole-3-yl) methyl, (1H-imidazol-4-yl) methyl,-(CH2) eCOR3'', aryl, and aryl C1-3 alkyl, the aryl group is Is it optionally substituted with a group selected from hydroxyl, C1-10 alkyl, C1-6 alkoxy, halogen, nitro, and cyano, or (ii) R3a and R3b are both C1-6 alkyl, (iii). ) R3a and R3b are (CH2) f such that they together form a spiro ring, or (iv) R3a is hydrogen and R3b and R2 together contain adjacent N and C atoms. (CH2) n to form a cyclic ring, or (v) R3b to be hydrogen, and R3a and R2 together to form a cyclic ring containing adjacent N and C atoms. (CH2) n, c is 1 to 6, d is 0 to 2, e is 0 to 3, f is 2 to 5, n is 2 to 4, and R3'is , Independently hydrogen or C1-6 alkyl, R3'' is -OR'or -N (R3') 2), or (vi) R3a is H, R3b is H, CH3 , CH2CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, CH2-Indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C (O) NH2, CH2CH2COOH, CH2CH2C (O) NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC (NH) NH2, CH2-imidazol-4-yl, CH2OH, CH (OH) CH3, CH2 ((4'-OH) -Ph), CH2SH, or lower cycloalkyl or (viii) ) R3a is CH3, -CH2CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C (O) NH2, CH2CH2COOH, CH2CH2C (O) NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC (NH) NH2, CH2-imidazol-4-yl, CH2OH, CH (OH) CH3, CH2 ((4'-OH) -Ph), CH2SH, or lower cycloalkyl, where R3b is H And R3'is independently hydrogen or alkyl and includes, but is not limited to, C1-20 alkyl, C1-10 alkyl, or C1-6 alkyl, where R3'' is -OR'. Or -N (R3') 2), (d) R4 is hydrogen, C1-10 alkyl, C1-10 alkyl (optionally substituted with lower alkyl, alkoxy, or halogen), C1-10 haloalkyl, C3-10 cycloalkyl, cycloalkylalkyl, cyclohetero. Alkoxy, aminoacyl, di (lower alkyl) amino-lower alkyl, aryl (phenyl, etc.), heteroaryl (pyridinyl, etc.), substituted aryl, or substituted heteroaryl. (e) R5 is H, lower alkyl, CN, vinyl, O- (lower alkyl), hydroxyl lower alkyl, i.e.-(CH2) pOH, where p is 1-6 and hydroxylmethyl. Contains (CH2OH), CH2F, N3, CH2CN, CH2NH2, CH2NHCH3, CH2N (CH3) 2, alkynes (optionally substituted), or halogens containing F, Cl, Br, or I, provided that When X is OH, the base is cytosine, R6 is H, R5 cannot be N3, when X is OH, R6 is CH3 or CH2F, B is a purine base. , R5 cannot be H, (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN, (g) X is H, OH, F, OMe, halogen, NH2, or N3, (h) Y is OH, H, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, vinyl, N3, CN, Cl, Br, F, I, NO2, OC (O) O (C1-4) Alkyl), OC (O) O (C1-4 alkyl), OC (O) O (C2-4 alkynyl), OC (O) O (C2-4 alkenyl), OC1-10 haloalkyl, O (aminoacyl), O (C1-10 Acyl), O (C1-4 Alkyl), O (C2-4 Alkenyl), S (C1-4 Acyl), S (C1-4 Alkyl), S (C2-4 Alkinyl), S (C2 -4 alkenyl), SO (C1-4 acyl), SO (C1-4 alkyl), SO (C2-4 alkynyl), SO (C2-4 alkenyl), SO2 (C1-4 acyl), SO2 (C1-4) Alkyl), SO2 (C2-4 alkynyl), SO2 (C2-4 alkenyl), OS (O) 2 (C1-4 acyl), OS (O) 2 (C1-4 alkyl), OS (O) 2 (C2) -4 alkenyl), NH2, NH (C1-4 alkyl), NH (C2-4 alkenyl), NH (C2-4 alkynyl), NH (C1-4 acyl), N (C1-4 alkyl) 2, N ( C1-18 acyl) 2, alkyl, alkynyl, alkenyl, and vinyl are N3, CN, 1 to 3 halogens (Cl, Br, F, I), NO2, C (O) O (C1-4). Alkyl), C (O) O (C1-4 alkyl), C (O) O (C2-4 alkynyl), C (O) O (C2-4 alkenyl), O (C1-4 acyl), O (C1) -4 alkyl), O (C2-4 alkenyl), S (C1-4 acyl), S (C1-4 alkyl), S (C2-4 alkynyl), S (C2-4 alkenyl), SO (C1-4) Acyl), SO (C1-4 alkyl), SO (C2-4 alkynyl), SO (C2-4 alkenyl), SO2 (C1-4 acyl), SO2 (C1-4 alkyl), SO2 (C2-4 alkynyl) , SO2 (C2-4 alkenyl), OS (O) 2 (C1-4 acyl), OS (O) 2 (C1-4 alkyl), OS (O) 2 (C2-4 alkenyl),NH2, NH (C1-4 alkyl), NH (C2-4 alkenyl), NH (C2-4 alkynyl), NH (C1-4 acyl), N (C1-4 alkyl) 2, N (C1-4 acyl) Arbitrarily replaced by 2 (i) R10 is NH2, R11 is H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, CONHR', CONR'2, CH = CHCO2H , Or CH = CHCO2R', R'is a lower alkyl, lower cycloalkyl, or C (O) (lower alkyl), or, in the case of NR'2, each R'is concatenated and contains at least two carbon atoms. Contains at least one C atom forming a heterocycle (j) Z is N or CR12 R12 is H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of C1-C6, CO2R', CONH2, CONHR', CONR'2 , CH = CHCO2H, or CH = CHCO2R'.

0056The sixteenth aspect of the third embodiment is directed to the compound represented by the formula I-6. During the ceremony (a) R1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl, (b) R2 is hydrogen or CH3, (c) R3a is H, R3b is H, CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, CH2-indole-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C (O) NH2, CH2CH2COOH, CH2CH2C (O) NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC (NH) NH2, CH2-imidazol-4-yl, CH2OH, CH (OH) CH3, CH2 ((4'-OH) -Ph) , CH2SH, or lower cycloalkyl, (d) R4 is hydrogen, CH3, Et, iPr, nPr, nBu, 2-butyl, tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridine-2-yl, N-methyl-azetidine. -3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di (lower alkyl) amino-lower alkyl , (e) R5 is a halogen containing H, CN, CH3, OCH3, CH2OH, CH2F, F, Cl, Br, or I, except that when X is OH, R6 is CH3 or CH2F. R5 cannot be H, provided (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN, (g) X is H, OH, F, OCH3, Cl, Br, I, NH2, or N3, (h) Y is OH, H, CH3, vinyl, NH2, N3, CN, Cl, Br, F, I, OC (O) CH3, OCH3, (i) R10 is NH2, R11 is H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, CONHR', CONR'2, CH = CHCO2H , Or CH = CHCO2R', R'is a lower alkyl, lower cycloalkyl, or C (O) (lower alkyl), or, in the case of NR'2, each R'is concatenated and contains at least two carbon atoms. Contains at least one C atom forming a heterocycle (j) Z is N or CR12 R12 is H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of C1-C6, CO2R', CONH2, CONHR', CONR'2 , CH = CHCO2H, or CH = CHCO2R'.

0057The seventeenth aspect of the third embodiment is directed to a compound represented by formula I-6. During the ceremony (a) R1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl, (b) R2 is hydrogen or CH3, (c) R3a is H, R3b is H, CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, or lower cycloalkyl. (d) R4 is hydrogen, CH3, Et, iPr, nPr, nBu, 2-butyl, tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridine-2-yl, N-methyl-azetidine. -3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di (lower alkyl) amino-lower alkyl , (e) R5 is H, CN, CH2F, F, Cl, Br, or I, except that when X is OH, R6 is CH3 or CH2F and R5 cannot be H. As a condition, (f) R6 is H, CH3, CH2F, CHF2, CF3, or F, (g) X is H, OH, F, OCH3, F, Cl, Br, I, NH2, or N3, (h) Y is H, OH, CH3, F, Cl, Br, I, NH2 or N3, OCH3, or OC (O) CH3. (i) R10 is NH2, R11 is H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, CONHR', CONR'2, CH = CHCO2H , Or CH = CHCO2R', R'is a lower alkyl, lower cycloalkyl, or C (O) (lower alkyl), or, in the case of NR'2, each R'is concatenated and contains at least two carbon atoms. Contains at least one C atom forming a heterocycle (j) Z is N or CR12 R12 is H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of C1-C6, CO2R', CONH2, CONHR', CONR'2 , CH = CHCO2H, or CH = CHCO2R'.

0058The eighteenth aspect of the third embodiment is directed to the compound represented by the formula I-6. During the ceremony (a) R1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl, (b) R2 is hydrogen, (c) R3a is H, R3b is H, CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, or lower cycloalkyl. (d) R4 is hydrogen, CH3, Et, iPr, nPr, nBu, 2-butyl, tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridine-2-yl, N-methyl-azetidine. -3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di (lower alkyl) amino-lower alkyl , (e) R5 is H, provided that when X is OH, R6 is CH3 or CH2F and R5 cannot be H. (f) R6 is H, CH3, CH2F, CHF2, CF3, or F, (g) X is H, OH, OCH3, F, NH2, or N3, (h) Y is OH, NH2, OCH3, or OC (O) CH3, (i) R10 is NH2, R11 is H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, CONHR', CONR'2, CH = CHCO2H , Or CH = CHCO2R', R'is a lower alkyl, lower cycloalkyl, or C (O) (lower alkyl), or, in the case of NR'2, each R'is concatenated and contains at least two carbon atoms. Contains at least one C atom forming a heterocycle (j) Z is N or CR12 R12 is H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of C1-C6, CO2R', CONH2, CONHR', CONR'2 , CH = CHCO2H, or CH = CHCO2R'.

0059A nineteenth aspect of the third embodiment is directed to a compound of formula I-6. During the ceremony (a) R1 is hydrogen, methyl, phenyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl, (b) R2 is hydrogen, (c) R3a is H, R3b is H, CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, or lower cycloalkyl. (d) R4 is hydrogen, CH3, Et, iPr, nPr, nBu, 2-butyl, tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridine-2-yl, N-methyl-azetidine. -3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di (lower alkyl) amino-lower alkyl , (e) R5 is H, provided that when X is OH, R6 is CH3 or CH2F and R5 cannot be H. (f) R6 is H, CH3, CH2F, CHF2, CF3, or F, (g) X is H, OH, OCH3, F, NH2, or N3, (h) Y is OH, NH2, OCH3, or OC (O) CH3, (i) R10 is NH2, and R11 is independently H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, CONHR', CONR'2. , CH = CHCO2H, or CH = CHCO2R', R'is a lower alkyl, lower cycloalkyl, or C (O) (lower alkyl), or, in the case of NR'2, each R'is concatenated and contains at least two carbon atoms. Contains at least one C atom forming a heterocycle (j) Z is N or CR12 R12 is H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of C1-C6, CO2R', CONH2, CONHR', CONR'2 , CH = CHCO2H, or CH = CHCO2R'. The fourth embodiment of the present invention targets a compound represented by the formula I, in which the base is a structure represented by the above formula c, R11 is H, and R2, R3a, R3b, R4, R5, R6, X, and Y are defined in the section of the abstract of the invention above.

0060The first aspect of the fourth embodiment is directed to a compound represented by formula I-7.<img id="000016" he="62" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />During the ceremony (a) R1 is hydrogen, n-alkyl, branched alkyl, cycloalkyl, or aryl, including, but not limited to, phenyl or naphthyl, where phenyl or naphthyl is C1-6 alkyl, C2-6 alkoxy, C2-6 alkynyl, C1-6 alkoxy, F, Cl, Br, I, nitro, cyano, C1-6 haloalkyl, -N (R1) 2, C1-6 acylamino, -NHSO2 C1-6 alkyl, -SO2N (R1' ) 2, COR1'', and -SO2C1-6 alkyl optionally substituted (R1'is independently hydrogen, or alkyl, C1-20 alkyl, C1-10 alkyl , Or including, but not limited to, C1-6 alkyl, where R1'' is -OR'or -N (R1') 2), (b) R2 is hydrogen or CH3, (c) R3a and R3b are (i) hydrogen, C1-10 alkyl, cycloalkyl,-(CH2) c (NR3') 2, C1-6 hydroxyalkyl, -CH2SH,-(CH2) 2S (O) dMe. ,-(CH2) 3NHC (= NH) NH2,Independently selected from (1H-indole-3-yl) methyl, (1H-imidazol-4-yl) methyl,-(CH2) eCOR3'', aryl, and aryl C1-3 alkyl, the aryl group is Is it optionally substituted with a group selected from hydroxyl, C1-10 alkyl, C1-6 alkoxy, halogen, nitro, and cyano, or (ii) R3a and R3b are both C1-6 alkyl, (iii). ) R3a and R3b are (CH2) f such that they together form a spiro ring, or (iv) R3a is hydrogen and R3b and R2 together contain adjacent N and C atoms. (CH2) n to form a cyclic ring, or (v) R3b to be hydrogen, and R3a and R2 together to form a cyclic ring containing adjacent N and C atoms. (CH2) n, c is 1 to 6, d is 0 to 2, e is 0 to 3, f is 2 to 5, n is 2 to 4, and R3'is , Independently hydrogen or C1-6 alkyl, R3'' is -OR'or -N (R3') 2), or (vi) R3a is H, R3b is H, CH3 , CH2CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, CH2-Indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C (O) NH2, CH2CH2COOH, CH2CH2C (O) NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC (NH) NH2, CH2-imidazol-4-yl, CH2OH, CH (OH) CH3, CH2 ((4'-OH) -Ph), CH2SH, or lower cycloalkyl or (viii) ) R3a is CH3, -CH2CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C (O) NH2, CH2CH2COOH, CH2CH2C (O) NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC (NH) NH2, CH2-imidazol-4-yl, CH2OH, CH (OH) CH3, CH2 ((4'-OH) -Ph), CH2SH, or lower cycloalkyl, where R3b is H And R3'is independently hydrogen or alkyl and includes, but is not limited to, C1-20 alkyl, C1-10 alkyl, or C1-6 alkyl, where R3'' is -OR'. Or -N (R3') 2), (d) R4 is hydrogen, C1-10 alkyl, C1-10 alkyl (optionally substituted with lower alkyl, alkoxy, or halogen), C1-10 haloalkyl, C3-10 cycloalkyl, cycloalkylalkyl, cyclohetero. Alkoxy, aminoacyl, di (lower alkyl) amino-lower alkyl, aryl (phenyl, etc.), heteroaryl (pyridinyl, etc.), substituted aryl, or substituted heteroaryl. (e) R5 is H, lower alkyl, CN, vinyl, O- (lower alkyl), hydroxyl lower alkyl, i.e.-(CH2) pOH, where p is 1-6 and hydroxylmethyl. Contains (CH2OH), CH2F, N3, CH2CN, CH2NH2, CH2NHCH3, CH2N (CH3) 2, alkynes (optionally substituted), or halogens containing F, Cl, Br, or I, provided that When X is OH, the base is cytosine, R6 is H, R5 cannot be N3, when X is OH, R6 is CH3 or CH2F, B is a purine base. , R5 cannot be H, (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN, (g) X is H, OH, F, OMe, halogen, NH2, or N3, (h) Y is OH, H, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, vinyl, N3, CN, Cl, Br, F, I, NO2, OC (O) O (C1-4) Alkyl), OC (O) O (C1-4 alkyl), OC (O) O (C2-4 alkynyl), OC (O) O (C2-4 alkenyl), OC1-10 haloalkyl, O (aminoacyl), O (C1-10 Acyl), O (C1-4 Alkyl), O (C2-4 Alkenyl), S (C1-4 Acyl), S (C1-4 Alkyl), S (C2-4 Alkinyl), S (C2 -4 alkenyl), SO (C1-4 acyl), SO (C1-4 alkyl), SO (C2-4 alkynyl), SO (C2-4 alkenyl), SO2 (C1-4 acyl), SO2 (C1-4) Alkyl), SO2 (C2-4 alkynyl), SO2 (C2-4 alkenyl), OS (O) 2 (C1-4 acyl), OS (O) 2 (C1-4 alkyl), OS (O) 2 (C2) -4 alkenyl), NH2, NH (C1-4 alkyl), NH (C2-4 alkenyl), NH (C2-4 alkynyl), NH (C1-4 acyl), N (C1-4 alkyl) 2, N ( C1-18 acyl) 2, alkyl, alkynyl, alkenyl, and vinyl are N3, CN, 1 to 3 halogens (Cl, Br, F, I), NO2, C (O) O (C1-4). Alkyl), C (O) O (C1-4 alkyl), C (O) O (C2-4 alkynyl), C (O) O (C2-4 alkenyl), O (C1-4 acyl), O (C1) -4 alkyl), O (C2-4 alkenyl), S (C1-4 acyl), S (C1-4 alkyl), S (C2-4 alkynyl), S (C2-4 alkenyl), SO (C1-4) Acyl), SO (C1-4 alkyl), SO (C2-4 alkynyl), SO (C2-4 alkenyl), SO2 (C1-4 acyl), SO2 (C1-4 alkyl), SO2 (C2-4 alkynyl) , SO2 (C2-4 alkenyl), OS (O) 2 (C1-4 acyl), OS (O) 2 (C1-4 alkyl), OS (O) 2 (C2-4 alkenyl),NH2, NH (C1-4 alkyl), NH (C2-4 alkenyl), NH (C2-4 alkynyl), NH (C1-4 acyl), N (C1-4 alkyl) 2, N (C1-4 acyl) Arbitrarily replaced by 2 (i) R10 is H, F, Cl, Br, I, OH, OR', SH, SR', NH2, NHR', NR'2, lower alkyl of C1-C6, halogenation of C1-C6 (F) , Cl, Br, I) Lower alkyl, C2-C6 lower alkenyl, C2-C6 halogenation (F, Cl, Br, I) lower alkenyl, C2-C6 lower alkynyl<img id="000017" he="6" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />Halogenation of C2-C6 (F, Cl, Br, I) lower alkynyl, lower alkoxy of C1-C6, halogenation of C1-C6 (F, Cl, Br, I) lower alkoxy, CO2H, CO2R', CONH2, CONHR', CONR'2, CH = CHCO2H, or CH = CHCO2R', R'is optionally substituted alkyl, including, but not limited to, optionally substituted C1-20 alkyl, optionally substituted C1-10 alkyl, optionally substituted lower alkyl. , Arbitrarily substituted cycloalkyl, optionally substituted alkynyl of C2-C6, optionally substituted lower alkenyl of C2-C6, or optionally substituted acyl, C (O) alkyl, C Includes, but is not limited to, (O) (C1-20 alkyl), C (O) (C1-10 alkyl), or C (O) (lower alkyl), or, as an alternative, NR'2 , Each R'contains at least one C atom that is linked to form a heterocycle containing at least two carbon atoms. (j) Z is N or CR12 R12 is H, halogen (including F, Cl, Br, I), OH, OR', SH, SR', NH2, NHR', NR'2, NO2, lower alkyl of C1-C6, C1-C6. Halogenated (F, Cl, Br, I) lower alkyl, C2-C6 lower alkenyl, C2-C6 halogenated (F, Cl, Br, I) lower alkynyl, C2-C6 lower alkynyl, C2-C6 Halogenated (F, Cl, Br, I) lower alkynyl, C1-C6 lower alkoxy, C1-C6 halogenated (F, Cl, Br, I) lower alkoxy, CO2H, CO2R', CONH2, CONHR', CONR '2, CH = CHCO2H, or CH = CHCO2R', provided that R12 is not (i) -CCH, (ii) -C = CH2, or (iii) -NO2. ..

0061The second aspect of the fourth embodiment is directed to the compound represented by the formula I-7. During the ceremony (a) R1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl, (b) R2 is hydrogen or CH3, (c) R3a is H, R3b is H, CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, CH2-indole-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C (O) NH2, CH2CH2COOH, CH2CH2C (O) NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC (NH) NH2, CH2-imidazol-4-yl, CH2OH, CH (OH) CH3, CH2 ((4'-OH) -Ph) , CH2SH, or lower cycloalkyl, (d) R4 is hydrogen, CH3, Et, iPr, nPr, nBu, 2-butyl, tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridine-2-yl, N-methyl-azetidine. -3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di (lower alkyl) amino-lower alkyl , (e) R5 is a halogen containing H, CN, CH3, OCH3, CH2OH, CH2F, F, Cl, Br, or I, except that when X is OH, R6 is CH3 or CH2F. R5 cannot be H, provided (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN, (g) X is H, OH, F, OCH3, halogen, NH2, or N3, (h) Y is OH, H, CH3, vinyl, NH2, N3, CN, Cl, Br, F, I, OC (O) CH3, OCH3, (i) R10 is H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, CONHR', CONR'2, CH = CHCO2H, or CH = CHCO2R' Yes, R'is a lower alkyl, lower cycloalkyl, or C (O) (lower alkyl), or, in the case of NR'2, each R'is concatenated and contains at least two carbon atoms. Contains at least one C atom forming a heterocycle (j) Z is N or CR12 R12 is H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of C1-C6, CO2R', CONH2, CONHR', CONR'2 , CH = CHCO2H, or CH = CHCO2R', provided that R12 is not (i) -CCH, (ii) -C = CH2, or (iii) -NO2.

0062The third aspect of the third embodiment is directed to the compound represented by the formula I-7. During the ceremony (a) R1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl, (b) R2 is hydrogen or CH3, (c) R3a is H, R3b is H, CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, or lower cycloalkyl. (d) R4 is hydrogen, CH3, Et, iPr, nPr, nBu, 2-butyl, tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridine-2-yl, N-methyl-azetidine. -3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di (lower alkyl) amino-lower alkyl , (e) R5 is H, CN, CH2F, F, Cl, Br, or I, except that X is OH, R6 is CH3 or CH2F, and R5 cannot be H. As a condition (f) R6 is H, CH3, CH2F, CHF2, CF3, or F, (g) X is H, OH, F, OCH3, F, Cl, Br, I, NH2, or N3, (h) Y is H, OH, CH3, F, Cl, Br, I, NH2 or N3, OCH3, or OC (O) CH3. (i) R10 is H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, CONHR', CONR'2, CH = CHCO2H, or CH = CHCO2R' Yes, R'is a lower alkyl, lower cycloalkyl, or C (O) (lower alkyl), or, in the case of NR'2, each R'is concatenated and contains at least two carbon atoms. Contains at least one C atom forming a heterocycle (j) Z is N or CR12 R12 is H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of C1-C6, CO2R', CONH2, CONHR', CONR'2 , CH = CHCO2H, or CH = CHCO2R', provided that R12 is not (i) -CCH, (ii) -C = CH2, or (iii) -NO2.

0063The fourth aspect of the fourth embodiment is directed to the compound represented by the formula I-7. During the ceremony (a) R1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl, (b) R2 is hydrogen, (c) R3a is H, R3b is H, CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, or lower cycloalkyl. (d) R4 is hydrogen, CH3, Et, iPr, nPr, nBu, 2-butyl, tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridine-2-yl, N-methyl-azetidine. -3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di (lower alkyl) amino-lower alkyl , (e) R5 is H, provided that when X is OH, R6 is CH3 or CH2F and R5 cannot be H. (f) R6 is H, CH3, CH2F, CHF2, CF3, or F, (g) X is H, OH, OCH3, F, NH2, or N3, (h) Y is OH, NH2, OCH3, or OC (O) CH3, (i) R10 and R11 are H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, CONHR', CONR'2, CH = CHCO2H, or CH = CHCO2R. 'And R'is a lower alkyl, lower cycloalkyl, or C (O) (lower alkyl), or, in the case of NR'2, each R'is concatenated and contains at least two carbon atoms. Contains at least one C atom forming a heterocycle (j) Z is N or CR12 R12 is H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of C1-C6, CO2R', CONH2, CONHR', CONR'2 , CH = CHCO2H, or CH = CHCO2R', provided that R12 is not (i) -CCH, (ii) -C = CH2, or (iii) -NO2.

0064The fifth aspect of the fourth embodiment targets the compound represented by the formula I-7. During the ceremony (a) R1 is hydrogen, methyl, phenyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl, (b) R2 is hydrogen, (c) R3a is H, R3b is H, CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, or lower cycloalkyl. (d) R4 is hydrogen, CH3, Et, iPr, nPr, nBu, 2-butyl, tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridine-2-yl, N-methyl-azetidine. -3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di (lower alkyl) amino-lower alkyl , (e) R5 is H, provided that when X is OH, R6 is CH3 or CH2F and R5 cannot be H. (f) R6 is H, CH3, CH2F, CHF2, CF3, or F, (g) X is H, OH, OCH3, F, NH2, or N3, (h) Y is OH, NH2, OCH3, or OC (O) CH3, (i) R10 is H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, CONHR', CONR'2, CH = CHCO2H, or CH = CHCO2R' Yes, R'is a lower alkyl, lower cycloalkyl, or C (O) (lower alkyl), or, in the case of NR'2, each R'is concatenated and contains at least two carbon atoms. Contains at least one C atom forming a heterocycle (j) Z is N or CR12 R12 is H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of C1-C6, CO2R', CONH2, CONHR', CONR'2 , CH = CHCO2H, or CH = CHCO2R'.

0065The sixth aspect of the fourth embodiment is directed to the compound represented by the formula I-8.<img id="000018" he="66" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />During the ceremony (a) R1 is hydrogen, n-alkyl, branched alkyl, cycloalkyl, or aryl, including, but not limited to, phenyl or naphthyl, where phenyl or naphthyl is C1-6 alkyl, C2-6 alkoxy, C2-6 alkynyl, C1-6 alkoxy, F, Cl, Br, I, nitro, cyano, C1-6 haloalkyl, -N (R1) 2, C1-6 acylamino, -NHSO2 C1-6 alkyl, -SO2N (R1' ) 2, COR1'', and -SO2C1-6 alkyl optionally substituted (R1'is independently hydrogen, or alkyl, C1-20 alkyl, C1-10 alkyl , Or including, but not limited to, C1-6 alkyl, where R1'' is -OR'or -N (R1') 2), (b) R2 is hydrogen or CH3, (c) R3a and R3b are (i) hydrogen, C1-10 alkyl, cycloalkyl,-(CH2) c (NR3') 2, C1-6 hydroxyalkyl, -CH2SH,-(CH2) 2S (O) dMe. ,-(CH2) 3NHC (= NH) NH2,Independently selected from (1H-indole-3-yl) methyl, (1H-imidazol-4-yl) methyl,-(CH2) eCOR3'', aryl, and aryl C1-3 alkyl, the aryl group is Is it optionally substituted with a group selected from hydroxyl, C1-10 alkyl, C1-6 alkoxy, halogen, nitro, and cyano, or (ii) R3a and R3b are both C1-6 alkyl, (iii). ) R3a and R3b are (CH2) f such that they together form a spiro ring, or (iv) R3a is hydrogen and R3b and R2 together contain adjacent N and C atoms. (CH2) n to form a cyclic ring, or (v) R3b to be hydrogen, and R3a and R2 together to form a cyclic ring containing adjacent N and C atoms. (CH2) n, c is 1 to 6, d is 0 to 2, e is 0 to 3, f is 2 to 5, n is 2 to 4, and R3'is , Independently hydrogen or C1-6 alkyl, R3'' is -OR'or -N (R3') 2), or (vi) R3a is H, R3b is H, CH3 , CH2CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, CH2-Indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C (O) NH2, CH2CH2COOH, CH2CH2C (O) NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC (NH) NH2, CH2-imidazol-4-yl, CH2OH, CH (OH) CH3, CH2 ((4'-OH) -Ph), CH2SH, or lower cycloalkyl or (viii) ) R3a is CH3, -CH2CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C (O) NH2, CH2CH2COOH, CH2CH2C (O) NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC (NH) NH2, CH2-imidazol-4-yl, CH2OH, CH (OH) CH3, CH2 ((4'-OH) -Ph), CH2SH, or lower cycloalkyl, where R3b is H And R3'is independently hydrogen or alkyl and includes, but is not limited to, C1-20 alkyl, C1-10 alkyl, or C1-6 alkyl, where R3'' is -OR'. Or -N (R3') 2), (d) R4 is hydrogen, C1-10 alkyl, C1-10 alkyl (optionally substituted with lower alkyl, alkoxy, or halogen), C1-10 haloalkyl, C3-10 cycloalkyl, cycloalkylalkyl, cyclohetero. Alkoxy, aminoacyl, di (lower alkyl) amino-lower alkyl, aryl (phenyl, etc.), heteroaryl (pyridinyl, etc.), substituted aryl, or substituted heteroaryl. (e) R5 is H, lower alkyl, CN, vinyl, O- (lower alkyl), hydroxyl lower alkyl, i.e.-(CH2) pOH, where p is 1-6 and hydroxylmethyl. Contains (CH2OH), CH2F, N3, CH2CN, CH2NH2, CH2NHCH3, CH2N (CH3) 2, alkynes (optionally substituted), or halogens containing F, Cl, Br, or I, provided that When X is OH, the base is cytosine, R6 is H, R5 cannot be N3, when X is OH, R6 is CH3 or CH2F, B is a purine base. , R5 cannot be H, (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN, (g) X is H, OH, F, OMe, halogen, NH2, or N3, (h) Y is OH, H, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, vinyl, N3, CN, Cl, Br, F, I, NO2, OC (O) O (C1-4) Alkyl), OC (O) O (C2-4 alkynyl), OC (O) O (C2-4 alkenyl), OC1-10 haloalkyl, O (aminoacyl), O (C1-10 acyl), O (C1-4) Alkyl), O (C2-4 alkenyl), S (C1-4 acyl), S (C1-4 alkyl), S (C2-4 alkynyl), S (C2-4 alkenyl), SO (C1-4 acyl) , SO (C1-4 alkyl), SO (C2-4 alkynyl), SO (C2-4 alkenyl), SO2 (C1-4 acyl), SO2 (C1-4 alkyl), SO2 (C2-4 alkynyl), SO2 (C2-4 alkenyl), OS (O) 2 (C1-4 acyl), OS (O) 2 (C1-4 alkyl), OS (O) 2 (C2-4 alkenyl), NH2, NH (C1-4) Alkyl), NH (C2-4 alkenyl), NH (C2-4 alkynyl), NH (C1-4 acyl), N (C1-4 alkyl) 2, N (C1-18 acyl) 2, alkyl, Alkinyl, alkenyl, and vinyl are N3, CN, 1 to 3 halogens (Cl, Br, F, I), NO2, C (O) O (C1-4 alkyl), C (O) O (C1-4). Alkyl), C (O) O (C2-4 alkynyl), C (O) O (C2-4 alkenyl), O (C1-4 acyl), O (C1-4 alkyl), O (C2-4 alkenyl) , S (C1-4 acyl), S (C1-4 alkyl), S (C2-4 alkynyl), S (C2-4 alkenyl), SO (C1-4 acyl), SO (C1-4 alkyl), SO (C2-4 alkynyl), SO (C2-4 alkenyl), SO2 (C1-4 acyl), SO2 (C1-4 alkyl), SO2 (C2-4 alkynyl), SO2 (C2-4 alkenyl), OS (O) ) 2 (C1-4 acyl), OS (O) 2 (C1-4 alkyl), OS (O) 2 (C2-4 alkenyl), NH2, NH (C1-4 alkyl),Arbitrarily substituted with NH (C2-4 alkenyl), NH (C2-4 alkynyl), NH (C1-4 acyl), N (C1-4 alkyl) 2, N (C1-4 acyl) 2 (i) R10 is H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, CONHR', CONR'2, CH = CHCO2H, or CH = CHCO2R' Yes, R'is a lower alkyl, lower cycloalkyl, or C (O) (lower alkyl), or, in the case of NR'2, each R'is concatenated and contains at least two carbon atoms. Contains at least one C atom forming a heterocycle (j) Z is N or CR12 R12 is H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of C1-C6, CO2R', CONH2, CONHR', CONR'2 , CH = CHCO2H, or CH = CHCO2R', but when the base is represented by the structure c where R11 is hydrogen, R12 is (i) -CCH, (ii) -C = CH2, Or (iii)-provided that it is not NO2.

0066A seventh aspect of the fourth embodiment is directed to a compound of formula I-8. During the ceremony (a) R1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl, (b) R2 is hydrogen or CH3, (c) R3a is H, R3b is H, CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, CH2-indole-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C (O) NH2, CH2CH2COOH, CH2CH2C (O) NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC (NH) NH2, CH2-imidazol-4-yl, CH2OH, CH (OH) CH3, CH2 ((4'-OH) -Ph) , CH2SH, or lower cycloalkyl, (d) R4 is hydrogen, CH3, Et, iPr, nPr, nBu, 2-butyl, tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridine-2-yl, N-methyl-azetidine. -3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di (lower alkyl) amino-lower alkyl , (e) R5 is a halogen containing H, CN, CH3, OCH3, CH2OH, CH2F, F, Cl, Br, or I, except that when X is OH, R6 is CH3 or CH2F. R5 cannot be H, provided (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN, (g) X is H, OH, F, OCH3, halogen, NH2, or N3, (h) Y is OH, H, CH3, vinyl, NH2, N3, CN, Cl, Br, F, I, OC (O) CH3, OCH3, (i) R10 is H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, CONHR', CONR'2, CH = CHCO2H, or CH = CHCO2R' Yes, R'is a lower alkyl, lower cycloalkyl, or C (O) (lower alkyl), or, in the case of NR'2, each R'is concatenated and contains at least two carbon atoms. Contains at least one C atom forming a heterocycle (j) Z is N or CR12 R12 is H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of C1-C6, CO2R', CONH2, CONHR', CONR'2 , CH = CHCO2H, or CH = CHCO2R', provided that R12 is not (i) -CCH, (ii) -C = CH2, or (iii) -NO2.

0067The eighth aspect of the fourth embodiment is directed to the compound represented by the formula I-8. During the ceremony (a) R1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl, (b) R2 is hydrogen or CH3, (c) R3a is H, R3b is H, CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, or lower cycloalkyl. (d) R4 is hydrogen, CH3, Et, iPr, nPr, nBu, 2-butyl, tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridine-2-yl, N-methyl-azetidine. -3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di (lower alkyl) amino-lower alkyl , (e) R5 is H, CN, CH2F, F, Cl, Br, or I, except that when X is OH, R6 is CH3 or CH2F and R5 cannot be H. As a condition, (f) R6 is H, CH3, CH2F, CHF2, CF3, or F, (g) X is H, OH, F, OCH3, F, Cl, Br, I, NH2, or N3, (h) Y is H, OH, CH3, F, Cl, Br, I, NH2 or N3, OCH3, or OC (O) CH3. (i) R10 is H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, CONHR', CONR'2, CH = CHCO2H, or CH = CHCO2R' Yes, R'is a lower alkyl, lower cycloalkyl, or C (O) (lower alkyl), or, in the case of NR'2, each R'is concatenated and contains at least two carbon atoms. Contains at least one C atom forming a heterocycle (j) Z is N or CR12 R12 is H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of C1-C6, CO2R', CONH2, CONHR', CONR'2 , CH = CHCO2H, or CH = CHCO2R', provided that R12 is not (i) -CCH, (ii) -C = CH2, or (iii) -NO2.

0068A ninth aspect of the fourth embodiment is directed to a compound of formula I-8. During the ceremony (a) R1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl, (b) R2 is hydrogen, (c) R3a is H, R3b is H, CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, or lower cycloalkyl. (d) R4 is hydrogen, CH3, Et, iPr, nPr, nBu, 2-butyl, tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridine-2-yl, N-methyl-azetidine. -3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di (lower alkyl) amino-lower alkyl , (e) R5 is H, provided that when X is OH, R6 is CH3 or CH2F and R5 cannot be H. (f) R6 is H, CH3, CH2F, CHF2, CF3, or F, (g) X is H, OH, OCH3, F, NH2, or N3, (h) Y is OH, NH2, OCH3, or OC (O) CH3, (i) R10 is H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, CONHR', CONR'2, CH = CHCO2H, or CH = CHCO2R' Yes, R'is a lower alkyl, lower cycloalkyl, or C (O) (lower alkyl), or, in the case of NR'2, each R'is concatenated and contains at least two carbon atoms. Contains at least one C atom forming a heterocycle (j) Z is N or CR12 R12 is H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of C1-C6, CO2R', CONH2, CONHR', CONR'2 , CH = CHCO2H, or CH = CHCO2R', provided that R12 is not (i) -CCH, (ii) -C = CH2, or (iii) -NO2.

0069The tenth aspect of the fourth embodiment is directed to a compound represented by the formula I-8. During the ceremony (a) R1 is hydrogen, methyl, phenyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl, (b) R2 is hydrogen, (c) R3a is H, R3b is H, CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, or lower cycloalkyl. (d) R4 is hydrogen, CH3, Et, iPr, nPr, nBu, 2-butyl, tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridine-2-yl, N-methyl-azetidine. -3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di (lower alkyl) amino-lower alkyl , (e) R5 is H, provided that when X is OH, R6 is CH3 or CH2F and R5 cannot be H. (f) R6 is H, CH3, CH2F, CHF2, CF3, or F, (g) X is H, OH, OCH3, F, NH2, or N3, (h) Y is OH, NH2, OCH3, or OC (O) CH3, (i) R10 is H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, CONHR', CONR'2, CH = CHCO2H, or CH = CHCO2R' Yes, R'is a lower alkyl, lower cycloalkyl, or C (O) (lower alkyl), or, in the case of NR'2, each R'is concatenated and contains at least two carbon atoms. Contains at least one C atom forming a heterocycle (j) Z is N or CR12 R12 is H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of C1-C6, CO2R', CONH2, CONHR', CONR'2 , CH = CHCO2H, or CH = CHCO2R', provided that R12 is not (i) -CCH, (ii) -C = CH2, or (iii) -NO2.

0070The fifth embodiment of the present invention targets a compound represented by the formula I, in which the base has a structure represented by the above formula d, and has a structure represented by the above formula d, R1, R2, R3a, R3b, R4, R5, R6, X, and Y are defined in the section of the abstract of the invention above. The first aspect of the fifth embodiment is directed to a compound represented by formula I-9.<img id="000019" he="62" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />During the ceremony (a) R1 is hydrogen, n-alkyl, branched alkyl, cycloalkyl, or aryl, including, but not limited to, phenyl or naphthyl, where phenyl or naphthyl is C1-6 alkyl, C2-6 alkoxy, C2-6 alkynyl, C1-6 alkoxy, F, Cl, Br, I, nitro, cyano, C1-6 haloalkyl, -N (R1) 2, C1-6 acylamino, -NHSO2 C1-6 alkyl, -SO2N (R1' ) 2, COR1'', and -SO2C1-6 alkyl optionally substituted (R1'is independently hydrogen, or alkyl, C1-20 alkyl, C1-10 alkyl , Or including, but not limited to, C1-6 alkyl, where R1'' is -OR'or -N (R1') 2), (b) R2 is hydrogen or CH3, (c) R3a and R3b are (i) hydrogen, C1-10 alkyl, cycloalkyl,-(CH2) c (NR3') 2, C1-6 hydroxyalkyl, -CH2SH,-(CH2) 2S (O) dMe. ,-(CH2) 3NHC (= NH) NH2,Independently selected from (1H-indole-3-yl) methyl, (1H-imidazol-4-yl) methyl,-(CH2) eCOR3'', aryl, and aryl C1-3 alkyl, the aryl group is Is it optionally substituted with a group selected from hydroxyl, C1-10 alkyl, C1-6 alkoxy, halogen, nitro, and cyano, or (ii) R3a and R3b are both C1-6 alkyl, (iii). ) R3a and R3b are (CH2) f such that they together form a spiro ring, or (iv) R3a is hydrogen and R3b and R2 together contain adjacent N and C atoms. (CH2) n to form a cyclic ring, or (v) R3b to be hydrogen, and R3a and R2 together to form a cyclic ring containing adjacent N and C atoms. (CH2) n, c is 1 to 6, d is 0 to 2, e is 0 to 3, f is 2 to 5, n is 2 to 4, and R3'is , Independently hydrogen or C1-6 alkyl, R3'' is -OR'or -N (R3') 2), or (vi) R3a is H, R3b is H, CH3 , CH2CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, CH2-Indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C (O) NH2, CH2CH2COOH, CH2CH2C (O) NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC (NH) NH2, CH2-imidazol-4-yl, CH2OH, CH (OH) CH3, CH2 ((4'-OH) -Ph), CH2SH, or lower cycloalkyl or (viii) ) R3a is CH3, -CH2CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C (O) NH2, CH2CH2COOH, CH2CH2C (O) NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC (NH) NH2, CH2-imidazol-4-yl, CH2OH, CH (OH) CH3, CH2 ((4'-OH) -Ph), CH2SH, or lower cycloalkyl, where R3b is H And R3'is independently hydrogen or alkyl and includes, but is not limited to, C1-20 alkyl, C1-10 alkyl, or C1-6 alkyl, where R3'' is -OR'. Or -N (R3') 2), (d) R4 is hydrogen, C1-10 alkyl, C1-10 alkyl (optionally substituted with lower alkyl, alkoxy, or halogen), C1-10 haloalkyl, C3-10 cycloalkyl, cycloalkylalkyl, cyclohetero. Alkoxy, aminoacyl, di (lower alkyl) amino-lower alkyl, aryl (phenyl, etc.), heteroaryl (pyridinyl, etc.), substituted aryl, or substituted heteroaryl. (e) R5 is H, lower alkyl, CN, vinyl, O- (lower alkyl), hydroxyl lower alkyl, i.e.-(CH2) pOH, where p is 1-6 and hydroxylmethyl. Contains (CH2OH), CH2F, N3, CH2CN, CH2NH2, CH2NHCH3, CH2N (CH3) 2, alkynes (optionally substituted), or halogens containing F, Cl, Br, or I, provided that When X is OH, the base is cytosine, R6 is H, R5 cannot be N3, when X is OH, R6 is CH3 or CH2F, B is a purine base. , R5 cannot be H, (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN, (g) X is H, OH, F, OMe, halogen, NH2, or N3, (h) Y is OH, H, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl,Vinyl, N3, CN, Cl, Br, F, I, NO2, OC (O) O (C1-4 alkyl), OC (O) O (C1-4 alkyl), OC (O) O (C2-4 alkylinyl) ), OC (O) O (C2-4 alkenyl), OC1-10 haloalkyl, O (amino acyl), O (C1-10 acyl), O (C1-4 alkyl), O (C2-4 alkenyl), S ( C1-4 acyl), S (C1-4 alkyl), S (C2-4 alkynyl), S (C2-4 alkenyl), SO (C1-4 acyl), SO (C1-4 alkyl), SO (C2-C2- 4 alkynyl), SO (C2-4 alkenyl), SO2 (C1-4 acyl), SO2 (C1-4 alkyl), SO2 (C2-4 alkynyl), SO2 (C2-4 alkenyl), OS (O) 2 ( C1-4 acyl), OS (O) 2 (C1-4 alkyl), OS (O) 2 (C2-4 alkenyl), NH2, NH (C1-4 alkyl), NH (C2-4 alkenyl), NH ( C2-4 alkynyl), NH (C1-4 acyl), N (C1-4 alkyl) 2, N (C1-18 acyl) 2, alkyl, alkynyl, alkenyl, and vinyl from N3, CN, 1 3 halogens (Cl, Br, F, I), NO2, C (O) O (C1-4 alkyl), C (O) O (C1-4 alkyl), C (O) O (C2-4 alkylyl) , C (O) O (C2-4 alkenyl), O (C1-4 acyl), O (C1-4 alkyl), O (C2-4 alkenyl), S (C1-4 acyl), S (C1-4) Alkyl), S (C2-4 alkynyl), S (C2-4 alkenyl), SO (C1-4 acyl), SO (C1-4 alkyl), SO (C2-4 alkynyl), SO (C2-4 alkenyl) , SO2 (C1-4 acyl), SO2 (C1-4 alkyl), SO2 (C2-4 alkynyl), SO2 (C2-4 alkenyl), OS (O) 2 (C1-4 acyl), OS (O) 2 (C1-4 alkyl), OS (O) 2 (C2-4 alkenyl), NH2, NH (C1-4 alkyl), NH (C2-4 alkenyl), NH (C2-4 alkini), NH (C1-4 acyl), N (C1-4 alkyl) 2, N (C1-4 acyl) 2 arbitrarily substituted.

0071The second aspect of the fifth embodiment is directed to the compound represented by the formula I-9. During the ceremony (a) R1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl, (b) R2 is hydrogen or CH3, (c) R3a is H, R3b is H, CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, CH2-indole-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C (O) NH2, CH2CH2COOH, CH2CH2C (O) NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC (NH) NH2, CH2-imidazol-4-yl, CH2OH, CH (OH) CH3, CH2 ((4'-OH) -Ph) , CH2SH, or lower cycloalkyl, (d) R4 is hydrogen, CH3, Et, iPr, nPr, nBu, 2-butyl, tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridine-2-yl, N-methyl-azetidine. -3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di (lower alkyl) amino-lower alkyl , (e) R5 is a halogen containing H, CN, CH3, OCH3, CH2OH, CH2F, F, Cl, Br, or I, except that when X is OH, R6 is CH3 or CH2F. R5 cannot be H, provided (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN, (g) X is H, OH, F, OCH3, halogen, NH2, or N3, (h) Y is OH, H, CH3, vinyl, NH2, N3, CN, Cl, Br, F, I, OC (O) CH3, OCH3,

0072The third aspect of the fifth embodiment is directed to the compound represented by the formula I-9. During the ceremony (a) R1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl, (b) R2 is hydrogen or CH3, (c) R3a is H, R3b is H, CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, or lower cycloalkyl. (d) R4 is hydrogen, CH3, Et, iPr, nPr, nBu, 2-butyl, tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridine-2-yl, N-methyl-azetidine. -3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di (lower alkyl) amino-lower alkyl , (e) R5 is H, CN, CH2F, F, Cl, Br, or I, except that X is OH, R6 is CH3 or CH2F, and R5 cannot be H. As a condition (f) R6 is H, CH3, CH2F, CHF2, CF3, or F, (g) X is H, OH, F, OCH3, F, Cl, Br, I, NH2, or N3, (h) Y is H, OH, CH3, F, Cl, Br, I, NH2 or N3, OCH3, or OC (O) CH3.

0073The fourth aspect of the fifth embodiment is directed to the compound represented by the formula I-9. During the ceremony (a) R1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl, (b) R2 is hydrogen, (c) R3a is H, R3b is H, CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, or lower cycloalkyl. (d) R4 is hydrogen, CH3, Et, iPr, nPr, nBu, 2-butyl, tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridine-2-yl, N-methyl-azetidine. -3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di (lower alkyl) amino-lower alkyl , (e) R5 is H, provided that when X is OH, R6 is CH3 or CH2F and R5 cannot be H. (f) R6 is H, CH3, CH2F, CHF2, CF3, or F, (g) X is H, OH, OCH3, F, NH2, or N3, (h) Y is OH, NH2, OCH3, or OC (O) CH3,

0074A fifth aspect of the fifth embodiment is directed to a compound represented by formula I-9. During the ceremony (a) R1 is hydrogen, methyl, phenyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl, (b) R2 is hydrogen, (c) R3a is H, R3b is H, CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, or lower cycloalkyl. (d) R4 is hydrogen, CH3, Et, iPr, nPr, nBu, 2-butyl, tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridine-2-yl, N-methyl-azetidine. -3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di (lower alkyl) amino-lower alkyl , (e) R5 is H, provided that when X is OH, R6 is CH3 or CH2F and R5 cannot be H. (f) R6 is H, CH3, CH2F, CHF2, CF3, or F, (g) X is H, OH, OCH3, F, NH2, or N3, (h) Y is OH, NH2, OCH3, or OC (O) CH3,

0075The sixth aspect of the fifth embodiment is directed to the compound represented by the formula I-10.<img id="000020" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />During the ceremony (a) R1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, or substituted or unsubstituted phenyl, and the substituents of the substituted phenyl are CH3, OCH3, F, Cl, Br, I, nitro. , Cyano, and CH3-qXq (in the formula, X is F, Cl, Br, or I, q is 1-3), (b) R2 is hydrogen or CH3, (c) R3a is H, R3b is H, CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C (O) NH2, CH2CH2COOH, CH2CH2C (O) NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC (NH) NH2, CH2-imidazol-4-yl, CH2OH, CH (OH) CH3, CH2 ((4'-OH) -Ph) , CH2SH, or lower cycloalkyl, or R3a is CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C (O) NH2, CH2CH2COOH, CH2CH2C (O) NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC (NH) NH2, CH2-imidazol-4-yl, CH2OH, CH (OH) CH3, CH2 ((4'-OH) -Ph) , CH2SH, or lower cycloalkyl, R3b is H, (d) R4 is hydrogen, CH3, Et, iPr, nPr, nBu, 2-butyl, tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridine-2-yl, N-methyl-azetidine. -3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di (lower alkyl) amino-lower alkyl , (e) R5 is a halogen containing H, CN, CH3, OCH3, CH2OH, CH2F, N3, CH2CN, CH2N3, CH2NH2, CH2NHCH3, CH2N (CH3) 2, F, Cl, Br, or I. , X is OH, provided that R6 is CH3 or CH2F and R5 cannot be H. (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN, (g) X is H, OH, F, OCH3, Cl, Br, I, NH2, or N3, (h) Y is OH, H, CH3, vinyl, N3, CN, Cl, Br, F, I, OC (O) CH3, OCH3, NH2, NHCH3, NH (vinyl), NH (acetyl), NH ( C (O) CH3), N (CH3) 2, N (C (O) CH3) 2,

0076The seventh aspect of the fifth embodiment is directed to the compound represented by the formula I-10. During the ceremony (a) R1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl, (b) R2 is hydrogen or CH3, (c) R3a is H, R3b is H, CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, CH2-indole-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C (O) NH2, CH2CH2COOH, CH2CH2C (O) NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC (NH) NH2, CH2-imidazol-4-yl, CH2OH, CH (OH) CH3, CH2 ((4'-OH) -Ph) , CH2SH, or lower cycloalkyl, (d) R4 is hydrogen, CH3, Et, iPr, nPr, nBu, 2-butyl, tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridine-2-yl, N-methyl-azetidine. -3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di (lower alkyl) amino-lower alkyl , (e) R5 is a halogen containing H, CN, CH3, OCH3, CH2OH, CH2F, F, Cl, Br, or I, except that when X is OH, R6 is CH3 or CH2F. R5 cannot be H, provided (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN, (g) X is H, OH, F, OCH3, Cl, Br, I, NH2, or N3, (h) Y is OH, H, CH3, vinyl, NH2, N3, CN, Cl, Br, F, I, OC (O) CH3, OCH3.

0077The eighth aspect of the fifth embodiment is directed to the compound represented by the formula I-10. During the ceremony (a) R1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl, (b) R2 is hydrogen or CH3, (c) R3a is H, R3b is H, CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, or lower cycloalkyl. (d) R4 is hydrogen, CH3, Et, iPr, nPr, nBu, 2-butyl, tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridine-2-yl, N-methyl-azetidine. -3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di (lower alkyl) amino-lower alkyl , (e) R5 is H, CN, CH2F, F, Cl, Br, or I, except that when X is OH, R6 is CH3 or CH2F and R5 cannot be H. As a condition, (f) R6 is H, CH3, CH2F, CHF2, CF3, or F, (g) X is H, OH, F, OCH3, F, Cl, Br, I, NH2, or N3, (h) Y is H, OH, CH3, F, Cl, Br, I, NH2 or N3, OCH3, or OC (O) CH3.

0078A ninth aspect of the fifth embodiment is directed to a compound of formula I-10. During the ceremony (a) R1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl, (b) R2 is hydrogen, (c) R3a is H, R3b is H, CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, or lower cycloalkyl. (d) R4 is hydrogen, CH3, Et, iPr, nPr, nBu, 2-butyl, tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridine-2-yl, N-methyl-azetidine. -3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di (lower alkyl) amino-lower alkyl , (e) R5 is H, provided that when X is OH, R6 is CH3 or CH2F and R5 cannot be H. (f) R6 is H, CH3, CH2F, CHF2, CF3, or F, (g) X is H, OH, OCH3, F, NH2, or N3, (h) Y is OH, NH2, OCH3, or OC (O) CH3,

0079The tenth aspect of the fifth embodiment is directed to the compound represented by the formula I-10. During the ceremony (a) R1 is hydrogen, methyl, phenyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl, (b) R2 is hydrogen, (c) R3a is H, R3b is H, CH3, CH (CH3) 2, CH2CH (CH3) 2, CH (CH3) CH2CH3, CH2Ph, or lower cycloalkyl. (d) R4 is hydrogen, CH3, Et, iPr, nPr, nBu, 2-butyl, tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridine-2-yl, N-methyl-azetidine. -3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di (lower alkyl) amino-lower alkyl , (e) R5 is H, provided that when X is OH, R6 is CH3 or CH2F and R5 cannot be H. (f) R6 is H, CH3, CH2F, CHF2, CF3, or F, (g) X is H, OH, OCH3, F, NH2, or N3, (h) Y is OH, NH2, OCH3, or OC (O) CH3. The table below contains the numerical identifiers associated with the various substituent names that should be viewed in the light of the accompanying structure. These structures are the intended species of various aspects of the disclosed embodiments and are not intended to limit the complete range of the intended compounds represented by the structure of formula I. However, any one of the illustrated nucleoside bases specifies a particular combination of R1, R2, R3a, R3b, R4, R5, R6, X, and Y. It is intended that it can be used in combination with one. In each of the presented tables, phosphoramidate substituents containing the substituents R3a and R3b are depicted regardless of their stereochemical structure (Structures I-1, I-3, I-5, I above). See -7 and I-9). The compounds listed below are intended to embody compounds in which R3a projects toward the observer, while R3b projects away from the observer (Structures I-2, I-4, I-6, I). -8, and I-10). In addition, the compounds listed below are also intended to embody compounds in which R3a projects away from the observer, while R3b projects toward the observer. Although not intended to be limiting, the preferred compound is one in which R3a projects towards the observer, while R3b projects away from the observer, as the natural L-amino acid (S) configuration is presented. Is intended. Furthermore, we recognize that the phosphorus atom of the phosphoramidate moiety is another source of antipodality. Although the following structure does not specifically describe the antipathy in phosphorus, we found that in the staggered (or zigzag) linear structure, the oxo-substituents protrude toward the observer, while OR1 Substituents project away from the observer and vice versa, that is, a stereochemical arrangement is possible in which the stereochemical representation of phosphorus's Cahn-Ingold-Prelog is either R or S. Recognize that. Therefore, the structure below is all possible solids for phosphorus.

0080<img id="000021" he="84" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />Table II-1<img id="000022" he="68" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table II-2<img id="000023" he="61" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table II-3<img id="000024" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table II-4<img id="000025" he="62" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table II-5<img id="000026" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table II-6<img id="000027" he="65" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table II-7<img id="000028" he="65" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table II-8<img id="000029" he="66" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table II-9<img id="000030" he="69" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table II-10<img id="000031" he="66" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table II-11<img id="000032" he="61" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table II-12<img id="000033" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table II-13<img id="000034" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table II-14<img id="000035" he="72" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table II-15<img id="000036" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table II-16<img id="000037" he="68" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table II-17<img id="000038" he="65" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table II-18<img id="000039" he="66" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table II-19<img id="000040" he="65" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table II-20<img id="000041" he="67" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table II-21<img id="000042" he="65" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table II-22<img id="000043" he="61" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table II-23<img id="000044" he="63" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table II-24<img id="000045" he="61" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table II-25<img id="000046" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table II-26<img id="000047" he="66" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table II-27<img id="000048" he="66" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table II-28<img id="000049" he="66" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table II-29<img id="000050" he="64" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table II-30<img id="000051" he="72" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table II-31<img id="000052" he="66" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table II-32<img id="000053" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table II-33<img id="000054" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table II-34<img id="000055" he="65" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table II-35<img id="000056" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table II-36<img id="000057" he="66" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table II-37<img id="000058" he="65" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table II-38<img id="000059" he="66" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table II-39<img id="000060" he="64" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table II-40<img id="000061" he="65" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table II-41<img id="000062" he="68" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table II-42<img id="000063" he="61" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table II-43<img id="000064" he="63" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table II-44<img id="000065" he="61" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table II-45<img id="000066" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table II-46<img id="000067" he="66" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table II-47<img id="000068" he="66" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table II-48<img id="000069" he="66" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table II-49<img id="000070" he="65" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table II-50<img id="000071" he="67" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring.

0081<img id="000072" he="78" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />Table III-1<img id="000073" he="61" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table III-2<img id="000074" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table III-3<img id="000075" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table III-4<img id="000076" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table III-5<img id="000077" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table III-6<img id="000078" he="66" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table III-7<img id="000079" he="67" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table III-8<img id="000080" he="64" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table III-9<img id="000081" he="66" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table III-10<img id="000082" he="66" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table III-11<img id="000083" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table III-12<img id="000084" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table III-13<img id="000085" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table III-14<img id="000086" he="61" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table III-15<img id="000087" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table III-16<img id="000088" he="66" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table III-17<img id="000089" he="65" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table III-18<img id="000090" he="65" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table III-19<img id="000091" he="64" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table III-20<img id="000092" he="67" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table III-21<img id="000093" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table III-22<img id="000094" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table III-23<img id="000095" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table III-24<img id="000096" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table III-25<img id="000097" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table III-26<img id="000098" he="68" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table III-27<img id="000099" he="65" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table III-28<img id="000100" he="65" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table III-29<img id="000101" he="66" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table III-30<img id="000102" he="66" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table III-31<img id="000103" he="65" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table III-32<img id="000104" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table III-33<img id="000105" he="61" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table III-34<img id="000106" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table III-35<img id="000107" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table III-36<img id="000108" he="65" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table III-37<img id="000109" he="65" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table III-38<img id="000110" he="66" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table III-39<img id="000111" he="66" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table III-40<img id="000112" he="65" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table III-41<img id="000113" he="61" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table III-42<img id="000114" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table III-43<img id="000115" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table III-44<img id="000116" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table III-45<img id="000117" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table III-46<img id="000118" he="67" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table III-47<img id="000119" he="64" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table III-48<img id="000120" he="64" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table III-49<img id="000121" he="70" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table III-50<img id="000122" he="66" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring.

0082<img id="000123" he="72" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />Table IV-1<img id="000124" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IV-2<img id="000125" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IV-3<img id="000126" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IV-4<img id="000127" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IV-5<img id="000128" he="61" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IV-6<img id="000129" he="67" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IV-7<img id="000130" he="64" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IV-8<img id="000131" he="69" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IV-9<img id="000132" he="66" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IV-10<img id="000133" he="65" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IV-11<img id="000134" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IV-12<img id="000135" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IV-13<img id="000136" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IV-14<img id="000137" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IV-15<img id="000138" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IV-16<img id="000139" he="66" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IV-17<img id="000140" he="61" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IV-18<img id="000141" he="64" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IV-19<img id="000142" he="66" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IV-20<img id="000143" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IV-21<img id="000144" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IV-22<img id="000145" he="62" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IV-23<img id="000146" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IV-24<img id="000147" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IV-25<img id="000148" he="61" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IV-26<img id="000149" he="67" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IV-27<img id="000150" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IV-28<img id="000151" he="66" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IV-29<img id="000152" he="68" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IV-30<img id="000153" he="61" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IV-31<img id="000154" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IV-32<img id="000155" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IV-33<img id="000156" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IV-34<img id="000157" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IV-35<img id="000158" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IV-36<img id="000159" he="65" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IV-37<img id="000160" he="64" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IV-38<img id="000161" he="66" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IV-39<img id="000162" he="65" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IV-40<img id="000163" he="65" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IV-41<img id="000164" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IV-42<img id="000165" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IV-43<img id="000166" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IV-44<img id="000167" he="62" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IV-45<img id="000168" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IV-46<img id="000169" he="66" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IV-47<img id="000170" he="66" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IV-48<img id="000171" he="63" wi="158" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IV-49<img id="000172" he="66" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IV-50<img id="000173" he="61" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring.

0083<img id="000174" he="78" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />Table V-1<img id="000175" he="61" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table V-2<img id="000176" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table V-3<img id="000177" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table V-4<img id="000178" he="62" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table V-5<img id="000179" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table V-6<img id="000180" he="67" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table V-7<img id="000181" he="66" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table V-8<img id="000182" he="64" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table V-9<img id="000183" he="66" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table V-10<img id="000184" he="66" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table V-11<img id="000185" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table V-12<img id="000186" he="61" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table V-13<img id="000187" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table V-14<img id="000188" he="74" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table V-15<img id="000189" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table V-16<img id="000190" he="64" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table V-17<img id="000191" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table V-18<img id="000192" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table V-19<img id="000193" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table V-20<img id="000194" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table V-21<img id="000195" he="63" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table V-22<img id="000196" he="56" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table V-23<img id="000197" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table V-24<img id="000198" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table V-25<img id="000199" he="61" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table V-26<img id="000200" he="65" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table V-27<img id="000201" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table V-28<img id="000202" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table V-29<img id="000203" he="68" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table V-30<img id="000204" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table V-31<img id="000205" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table V-32<img id="000206" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table V-33<img id="000207" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table V-34<img id="000208" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table V-35<img id="000209" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table V-36<img id="000210" he="63" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table V-37<img id="000211" he="64" wi="158" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table V-38<img id="000212" he="63" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table V-39<img id="000213" he="63" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table V-40<img id="000214" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table V-41<img id="000215" he="63" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table V-42<img id="000216" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table V-43<img id="000217" he="62" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table V-44<img id="000218" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table V-45<img id="000219" he="62" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table V-46<img id="000220" he="66" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table V-47<img id="000221" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table V-48<img id="000222" he="65" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table V-49<img id="000223" he="64" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table V-50<img id="000224" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring.

0084<img id="000225" he="73" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />Table VI-1<img id="000226" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VI-2<img id="000227" he="61" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VI-3<img id="000228" he="61" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VI-4<img id="000229" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VI-5<img id="000230" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VI-6<img id="000231" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VI-7<img id="000232" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VI-8<img id="000233" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VI-9<img id="000234" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VI-10<img id="000235" he="60" wi="158" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VI-11<img id="000236" he="61" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VI-12<img id="000237" he="62" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VI-13<img id="000238" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VI-14<img id="000239" he="67" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VI-15<img id="000240" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VI-16<img id="000241" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VI-17<img id="000242" he="61" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VI-18<img id="000243" he="61" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VI-19<img id="000244" he="61" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VI-20<img id="000245" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VI-21<img id="000246" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VI-22<img id="000247" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VI-23<img id="000248" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VI-24<img id="000249" he="61" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VI-25<img id="000250" he="62" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VI-26<img id="000251" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VI-27<img id="000252" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VI-28<img id="000253" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VI-29<img id="000254" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VI-30<img id="000255" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VI-31<img id="000256" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VI-32<img id="000257" he="61" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VI-33<img id="000258" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VI-34<img id="000259" he="62" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VI-35<img id="000260" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VI-36<img id="000261" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VI-37<img id="000262" he="61" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VI-38<img id="000263" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VI-39<img id="000264" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VI-40<img id="000265" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VI-41<img id="000266" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VI-42<img id="000267" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VI-43<img id="000268" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VI-44<img id="000269" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VI-45<img id="000270" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VI-46<img id="000271" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VI-47<img id="000272" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VI-48<img id="000273" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VI-49<img id="000274" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VI-50<img id="000275" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring.

0085<img id="000276" he="71" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />Table VII-1<img id="000277" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VII-2<img id="000278" he="64" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VII-3<img id="000279" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VII-4<img id="000280" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VII-5<img id="000281" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VII-6<img id="000282" he="64" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VII-7<img id="000283" he="63" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VII-8<img id="000284" he="67" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VII-9<img id="000285" he="64" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VII-10<img id="000286" he="65" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VII-11<img id="000287" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VII-12<img id="000288" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VII-13<img id="000289" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VII-14<img id="000290" he="70" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VII-15<img id="000291" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VII-16<img id="000292" he="65" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VII-17<img id="000293" he="64" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VII-18<img id="000294" he="65" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VII-19<img id="000295" he="67" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VII-20<img id="000296" he="66" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VII-21<img id="000297" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VII-22<img id="000298" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VII-23<img id="000299" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VII-24<img id="000300" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VII-25<img id="000301" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VII-26<img id="000302" he="66" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VII-27<img id="000303" he="63" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VII-28<img id="000304" he="64" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VII-29<img id="000305" he="65" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VII-30<img id="000306" he="63" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VII-31<img id="000307" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VII-32<img id="000308" he="62" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VII-33<img id="000309" he="61" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VII-34<img id="000310" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VII-35<img id="000311" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VII-36<img id="000312" he="64" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VII-37<img id="000313" he="64" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VII-38<img id="000314" he="64" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VII-39<img id="000315" he="64" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VII-40<img id="000316" he="64" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VII-41<img id="000317" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VII-42<img id="000318" he="61" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VII-43<img id="000319" he="63" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VII-44<img id="000320" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VII-45<img id="000321" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VII-46<img id="000322" he="64" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VII-47<img id="000323" he="64" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VII-48<img id="000324" he="64" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VII-49<img id="000325" he="64" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VII-50<img id="000326" he="64" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring.

0086<img id="000327" he="71" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />Table VIII-1<img id="000328" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VIII-2<img id="000329" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VIII-3<img id="000330" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VIII-4<img id="000331" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VIII-5<img id="000332" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VIII-6<img id="000333" he="64" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VIII-7<img id="000334" he="64" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VIII-8<img id="000335" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VIII-9<img id="000336" he="64" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VIII-10<img id="000337" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VIII-11<img id="000338" he="62" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VIII-12<img id="000339" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VIII-13<img id="000340" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VIII-14<img id="000341" he="66" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VIII-15<img id="000342" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VIII-16<img id="000343" he="63" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VIII-17<img id="000344" he="61" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VIII-18<img id="000345" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VIII-19<img id="000346" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VIII-20<img id="000347" he="56" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VIII-21<img id="000348" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VIII-22<img id="000349" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VIII-23<img id="000350" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VIII-24<img id="000351" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VIII-25<img id="000352" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VIII-26<img id="000353" he="66" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VIII-27<img id="000354" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VIII-28<img id="000355" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VIII-29<img id="000356" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VIII-30<img id="000357" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VIII-31<img id="000358" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VIII-32<img id="000359" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VIII-33<img id="000360" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VIII-34<img id="000361" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VIII-35<img id="000362" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VIII-36<img id="000363" he="65" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VIII-37<img id="000364" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VIII-38<img id="000365" he="64" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VIII-39<img id="000366" he="63" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VIII-40<img id="000367" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VIII-41<img id="000368" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VIII-42<img id="000369" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VIII-43<img id="000370" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VIII-44<img id="000371" he="62" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VIII-45<img id="000372" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VIII-46<img id="000373" he="65" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VIII-47<img id="000374" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VIII-48<img id="000375" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VIII-49<img id="000376" he="61" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table VIII-50<img id="000377" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring.

0087<img id="000378" he="77" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />Table IX-1<img id="000379" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IX-2<img id="000380" he="61" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IX-3<img id="000381" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IX-4<img id="000382" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IX-5<img id="000383" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IX-6<img id="000384" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IX-7<img id="000385" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IX-8<img id="000386" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IX-9<img id="000387" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IX-10<img id="000388" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IX-11<img id="000389" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IX-12<img id="000390" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IX-13<img id="000391" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IX-14<img id="000392" he="65" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IX-15<img id="000393" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IX-16<img id="000394" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IX-17<img id="000395" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IX-18<img id="000396" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IX-19<img id="000397" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IX-20<img id="000398" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IX-21<img id="000399" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IX-22<img id="000400" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IX-23<img id="000401" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IX-24<img id="000402" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IX-25<img id="000403" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IX-26<img id="000404" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IX-27<img id="000405" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IX-28<img id="000406" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IX-29<img id="000407" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IX-30<img id="000408" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IX-31<img id="000409" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IX-32<img id="000410" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IX-33<img id="000411" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IX-34<img id="000412" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IX-35<img id="000413" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IX-36<img id="000414" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IX-37<img id="000415" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IX-38<img id="000416" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IX-39<img id="000417" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IX-40<img id="000418" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IX-41<img id="000419" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IX-42<img id="000420" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IX-43<img id="000421" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IX-44<img id="000422" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IX-45<img id="000423" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IX-46<img id="000424" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IX-47<img id="000425" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IX-48<img id="000426" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IX-49<img id="000427" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table IX-50<img id="000428" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring.

0088<img id="000429" he="72" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />Table X-1<img id="000430" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table X-2<img id="000431" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table X-3<img id="000432" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table X-4<img id="000433" he="56" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table X-5<img id="000434" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table X-6<img id="000435" he="61" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table X-7<img id="000436" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table X-8<img id="000437" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table X-9<img id="000438" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table X-10<img id="000439" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table X-11<img id="000440" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table X-12<img id="000441" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table X-13<img id="000442" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table X-14<img id="000443" he="70" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table X-15<img id="000444" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table X-16<img id="000445" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table X-17<img id="000446" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table X-18<img id="000447" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table X-19<img id="000448" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table X-20<img id="000449" he="61" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table X-21<img id="000450" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table X-22<img id="000451" he="57" wi="158" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table X-23<img id="000452" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table X-24<img id="000453" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table X-25<img id="000454" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table X-26<img id="000455" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table X-27<img id="000456" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table X-28<img id="000457" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table X-29<img id="000458" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table X-30<img id="000459" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table X-31<img id="000460" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table X-32<img id="000461" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table X-33<img id="000462" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table X-34<img id="000463" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table X-35<img id="000464" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table X-36<img id="000465" he="61" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table X-37<img id="000466" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table X-38<img id="000467" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table X-39<img id="000468" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table X-40<img id="000469" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table X-41<img id="000470" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table X-42<img id="000471" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table X-43<img id="000472" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table X-44<img id="000473" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table X-45<img id="000474" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table X-46<img id="000475" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table X-47<img id="000476" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table X-48<img id="000477" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table X-49<img id="000478" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table X-50<img id="000479" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring.

0089<img id="000480" he="75" wi="158" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />Table XI-1<img id="000481" he="61" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XI-2<img id="000482" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XI-3<img id="000483" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XI-4<img id="000484" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XI-5<img id="000485" he="61" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XI-6<img id="000486" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XI-7<img id="000487" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XI-8<img id="000488" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XI-9<img id="000489" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XI-10<img id="000490" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XI-11<img id="000491" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XI-12<img id="000492" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XI-13<img id="000493" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XI-14<img id="000494" he="66" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XI-15<img id="000495" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XI-16<img id="000496" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XI-17<img id="000497" he="61" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XI-18<img id="000498" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XI-19<img id="000499" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XI-20<img id="000500" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XI-21<img id="000501" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XI-22<img id="000502" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XI-23<img id="000503" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XI-24<img id="000504" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XI-25<img id="000505" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XI-26<img id="000506" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XI-27<img id="000507" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XI-28<img id="000508" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XI-29<img id="000509" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XI-30<img id="000510" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XI-31<img id="000511" he="62" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XI-32<img id="000512" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XI-33<img id="000513" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XI-34<img id="000514" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XI-35<img id="000515" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XI-36<img id="000516" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XI-37<img id="000517" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XI-38<img id="000518" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XI-39<img id="000519" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XI-40<img id="000520" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XI-41<img id="000521" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XI-42<img id="000522" he="61" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XI-43<img id="000523" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XI-44<img id="000524" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XI-45<img id="000525" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XI-46<img id="000526" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XI-47<img id="000527" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XI-48<img id="000528" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XI-49<img id="000529" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XI-50<img id="000530" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring.

0090<img id="000531" he="71" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />Table XII-1<img id="000532" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XII-2<img id="000533" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XII-3<img id="000534" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XII-4<img id="000535" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XII-5<img id="000536" he="61" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XII-6<img id="000537" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XII-7<img id="000538" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XII-8<img id="000539" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XII-9<img id="000540" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XII-10<img id="000541" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XII-11<img id="000542" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XII-12<img id="000543" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XII-13<img id="000544" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XII-14<img id="000545" he="65" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XII-15<img id="000546" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XII-16<img id="000547" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XII-17<img id="000548" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XII-18<img id="000549" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XII-19<img id="000550" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XII-20<img id="000551" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XII-21<img id="000552" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XII-22<img id="000553" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XII-23<img id="000554" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XII-24<img id="000555" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XII-25<img id="000556" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XII-26<img id="000557" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XII-27<img id="000558" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XII-28<img id="000559" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XII-29<img id="000560" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XII-30<img id="000561" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XII-31<img id="000562" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XII-32<img id="000563" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XII-33<img id="000564" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XII-34<img id="000565" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XII-35<img id="000566" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XII-36<img id="000567" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XII-37<img id="000568" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XII-38<img id="000569" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XII-39<img id="000570" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XII-40<img id="000571" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XII-41<img id="000572" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XII-42<img id="000573" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XII-43<img id="000574" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XII-44<img id="000575" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XII-45<img id="000576" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XII-46<img id="000577" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XII-47<img id="000578" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XII-48<img id="000579" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XII-49<img id="000580" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XII-50<img id="000581" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring.

0091<img id="000582" he="78" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />Table XIII-1<img id="000583" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIII-2<img id="000584" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIII-3<img id="000585" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIII-4<img id="000586" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIII-5<img id="000587" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIII-6<img id="000588" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIII-7<img id="000589" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIII-8<img id="000590" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIII-9<img id="000591" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIII-10<img id="000592" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIII-11<img id="000593" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIII-12<img id="000594" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIII-13<img id="000595" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIII-14<img id="000596" he="63" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIII-15<img id="000597" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIII-16<img id="000598" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIII-17<img id="000599" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIII-18<img id="000600" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIII-19<img id="000601" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIII-20<img id="000602" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIII-21<img id="000603" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIII-22<img id="000604" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIII-23<img id="000605" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIII-24<img id="000606" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIII-25<img id="000607" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIII-26<img id="000608" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIII-27<img id="000609" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIII-28<img id="000610" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIII-29<img id="000611" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIII-30<img id="000612" he="56" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIII-31<img id="000613" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIII-32<img id="000614" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIII-33<img id="000615" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIII-34<img id="000616" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIII-35<img id="000617" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIII-36<img id="000618" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIII-37<img id="000619" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIII-38<img id="000620" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIII-39<img id="000621" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIII-40<img id="000622" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIII-41<img id="000623" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIII-42<img id="000624" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIII-43<img id="000625" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIII-44<img id="000626" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIII-45<img id="000627" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIII-46<img id="000628" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIII-47<img id="000629" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIII-48<img id="000630" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIII-49<img id="000631" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIII-50<img id="000632" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring.

0092<img id="000633" he="70" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />Table XIV-1<img id="000634" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIV-2<img id="000635" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIV-3<img id="000636" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIV-4<img id="000637" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIV-5<img id="000638" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIV-6<img id="000639" he="61" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIV-7<img id="000640" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIV-8<img id="000641" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIV-9<img id="000642" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIV-10<img id="000643" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIV-11<img id="000644" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIV-12<img id="000645" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIV-13<img id="000646" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIV-14<img id="000647" he="66" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIV-15<img id="000648" he="58" wi="158" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIV-16<img id="000649" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIV-17<img id="000650" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIV-18<img id="000651" he="61" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIV-19<img id="000652" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIV-20<img id="000653" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIV-21<img id="000654" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIV-22<img id="000655" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIV-23<img id="000656" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIV-24<img id="000657" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIV-25<img id="000658" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIV-26<img id="000659" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIV-27<img id="000660" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIV-28<img id="000661" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIV-29<img id="000662" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIV-30<img id="000663" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIV-31<img id="000664" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIV-32<img id="000665" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIV-33<img id="000666" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIV-34<img id="000667" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIV-35<img id="000668" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIV-36<img id="000669" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIV-37<img id="000670" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIV-38<img id="000671" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIV-39<img id="000672" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIV-40<img id="000673" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIV-41<img id="000674" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIV-42<img id="000675" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIV-43<img id="000676" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIV-44<img id="000677" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIV-45<img id="000678" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIV-46<img id="000679" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIV-47<img id="000680" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIV-48<img id="000681" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIV-49<img id="000682" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIV-50<img id="000683" he="61" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring.

0093<img id="000684" he="76" wi="158" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />Table XV-1<img id="000685" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XV-2<img id="000686" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XV-3<img id="000687" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XV-4<img id="000688" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XV-5<img id="000689" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XV-6<img id="000690" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XV-7<img id="000691" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XV-8<img id="000692" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XV-9<img id="000693" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XV-10<img id="000694" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XV-11<img id="000695" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XV-12<img id="000696" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XV-13<img id="000697" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XV-14<img id="000698" he="65" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XV-15<img id="000699" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XV-16<img id="000700" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XV-17<img id="000701" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XV-18<img id="000702" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XV-19<img id="000703" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XV-20<img id="000704" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XV-21<img id="000705" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XV-22<img id="000706" he="61" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XV-23<img id="000707" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XV-24<img id="000708" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XV-25<img id="000709" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XV-26<img id="000710" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XV-27<img id="000711" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XV-28<img id="000712" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XV-29<img id="000713" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XV-30<img id="000714" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XV-31<img id="000715" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XV-32<img id="000716" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XV-33<img id="000717" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XV-34<img id="000718" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XV-35<img id="000719" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XV-36<img id="000720" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XV-37<img id="000721" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XV-38<img id="000722" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XV-39<img id="000723" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XV-40<img id="000724" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XV-41<img id="000725" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XV-42<img id="000726" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XV-43<img id="000727" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XV-44<img id="000728" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XV-45<img id="000729" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XV-46<img id="000730" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XV-47<img id="000731" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XV-48<img id="000732" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XV-49<img id="000733" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XV-50<img id="000734" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring.

0094<img id="000735" he="69" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />Table XVI-1<img id="000736" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVI-2<img id="000737" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVI-3<img id="000738" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVI-4<img id="000739" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVI-5<img id="000740" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVI-6<img id="000741" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVI-7<img id="000742" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVI-8<img id="000743" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVI-9<img id="000744" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVI-10<img id="000745" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVI-11<img id="000746" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVI-12<img id="000747" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVI-13<img id="000748" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVI-14<img id="000749" he="65" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVI-15<img id="000750" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVI-16<img id="000751" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVI-17<img id="000752" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVI-18<img id="000753" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVI-19<img id="000754" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVI-20<img id="000755" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVI-21<img id="000756" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVI-22<img id="000757" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVI-23<img id="000758" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVI-24<img id="000759" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVI-25<img id="000760" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVI-26<img id="000761" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVI-27<img id="000762" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVI-28<img id="000763" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVI-29<img id="000764" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVI-30<img id="000765" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVI-31<img id="000766" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVI-32<img id="000767" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVI-33<img id="000768" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVI-34<img id="000769" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVI-35<img id="000770" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVI-36<img id="000771" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVI-37<img id="000772" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVI-38<img id="000773" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVI-39<img id="000774" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVI-40<img id="000775" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVI-41<img id="000776" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVI-42<img id="000777" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVI-43<img id="000778" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVI-44<img id="000779" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVI-45<img id="000780" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVI-46<img id="000781" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVI-47<img id="000782" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVI-48<img id="000783" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVI-49<img id="000784" he="61" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVI-50<img id="000785" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring.

0095<img id="000786" he="68" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />Table XVII-1<img id="000787" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVII-2<img id="000788" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVII-3<img id="000789" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVII-4<img id="000790" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVII-5<img id="000791" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVII-6<img id="000792" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVII-7<img id="000793" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVII-8<img id="000794" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVII-9<img id="000795" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVII-10<img id="000796" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVII-11<img id="000797" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVII-12<img id="000798" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVII-13<img id="000799" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVII-14<img id="000800" he="63" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVII-15<img id="000801" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVII-16<img id="000802" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVII-17<img id="000803" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVII-18<img id="000804" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVII-19<img id="000805" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVII-20<img id="000806" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVII-21<img id="000807" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVII-22<img id="000808" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVII-23<img id="000809" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVII-24<img id="000810" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVII-25<img id="000811" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVII-26<img id="000812" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVII-27<img id="000813" he="61" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVII-28<img id="000814" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVII-29<img id="000815" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVII-30<img id="000816" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVII-31<img id="000817" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVII-32<img id="000818" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVII-33<img id="000819" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVII-34<img id="000820" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVII-35<img id="000821" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVII-36<img id="000822" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVII-37<img id="000823" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVII-38<img id="000824" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVII-39<img id="000825" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVII-40<img id="000826" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVII-41<img id="000827" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVII-42<img id="000828" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVII-43<img id="000829" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVII-44<img id="000830" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVII-45<img id="000831" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVII-46<img id="000832" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVII-47<img id="000833" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVII-48<img id="000834" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVII-49<img id="000835" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVII-50<img id="000836" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring.

0096<img id="000837" he="69" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />Table XVIII-1<img id="000838" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVIII-2<img id="000839" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVIII-3<img id="000840" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVIII-4<img id="000841" he="57" wi="158" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVIII-5<img id="000842" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVIII-6<img id="000843" he="63" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVIII-7<img id="000844" he="66" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVIII-8<img id="000845" he="63" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVIII-9<img id="000846" he="63" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVIII-10<img id="000847" he="64" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVIII-11<img id="000848" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVIII-12<img id="000849" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVIII-13<img id="000850" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVIII-14<img id="000851" he="64" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVIII-15<img id="000852" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVIII-16<img id="000853" he="62" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVIII-17<img id="000854" he="65" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVIII-18<img id="000855" he="63" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVIII-19<img id="000856" he="65" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVIII-20<img id="000857" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVIII-21<img id="000858" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVIII-22<img id="000859" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVIII-23<img id="000860" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVIII-24<img id="000861" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVIII-25<img id="000862" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVIII-26<img id="000863" he="64" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVIII-27<img id="000864" he="65" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVIII-28<img id="000865" he="63" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVIII-29<img id="000866" he="66" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVIII-30<img id="000867" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVIII-31<img id="000868" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVIII-32<img id="000869" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVIII-33<img id="000870" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVIII-34<img id="000871" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVIII-35<img id="000872" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVIII-36<img id="000873" he="65" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVIII-37<img id="000874" he="63" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVIII-38<img id="000875" he="64" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XVIII-39 * R2 and R3b are connected by (CH2) 3 to form a 5-membered ring.<img id="000876" he="65" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />Table XVIII-40 * R2 and R3b are connected by (CH2) 3 to form a 5-membered ring.<img id="000877" he="64" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />Table XVIII-41 * R2 and R3b are connected by (CH2) 3 to form a 5-membered ring.<img id="000878" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />Table XVIII-42 * R2 and R3b are connected by (CH2) 3 to form a 5-membered ring.<img id="000879" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />Table XVIII-43 * R2 and R3b are connected by (CH2) 3 to form a 5-membered ring.<img id="000880" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />Table XVIII-44 * R2 and R3b are connected by (CH2) 3 to form a 5-membered ring.<img id="000881" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />Table XVIII-45 * R2 and R3b are connected by (CH2) 3 to form a 5-membered ring.<img id="000882" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />Table XVIII-46 * R2 and R3b are connected by (CH2) 3 to form a 5-membered ring.<img id="000883" he="63" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />Table XVIII-47 * R2 and R3b are connected by (CH2) 3 to form a 5-membered ring.<img id="000884" he="63" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />Table XVIII-48 * R2 and R3b are connected by (CH2) 3 to form a 5-membered ring.<img id="000885" he="65" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />Table XVIII-49 * R2 and R3b are connected by (CH2) 3 to form a 5-membered ring.<img id="000886" he="64" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />Table XVIII-50 * R2 and R3b are connected by (CH2) 3 to form a 5-membered ring.<img id="000887" he="64" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />

0097<img id="000888" he="69" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />Table XIX-1<img id="000889" he="61" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIX-2<img id="000890" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIX-3<img id="000891" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIX-4<img id="000892" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIX-5<img id="000893" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIX-6<img id="000894" he="64" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIX-7<img id="000895" he="64" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIX-8<img id="000896" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIX-9<img id="000897" he="64" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIX-10<img id="000898" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIX-11<img id="000899" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIX-12<img id="000900" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIX-13<img id="000901" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIX-14<img id="000902" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIX-15<img id="000903" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIX-16<img id="000904" he="64" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIX-17<img id="000905" he="56" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIX-18<img id="000906" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIX-19<img id="000907" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIX-20<img id="000908" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIX-21<img id="000909" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIX-22<img id="000910" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIX-23<img id="000911" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIX-24<img id="000912" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIX-25<img id="000913" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIX-26<img id="000914" he="64" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIX-27<img id="000915" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIX-28<img id="000916" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIX-29<img id="000917" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIX-30<img id="000918" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIX-31<img id="000919" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIX-32<img id="000920" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIX-33<img id="000921" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIX-34<img id="000922" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIX-35<img id="000923" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIX-36<img id="000924" he="63" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIX-37<img id="000925" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIX-38<img id="000926" he="64" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIX-39<img id="000927" he="64" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIX-40<img id="000928" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIX-41<img id="000929" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIX-42<img id="000930" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIX-43<img id="000931" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIX-44<img id="000932" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIX-45<img id="000933" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIX-46<img id="000934" he="63" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIX-47<img id="000935" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIX-48<img id="000936" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIX-49<img id="000937" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XIX-50<img id="000938" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring.

0098<img id="000939" he="75" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />Table XX-1<img id="000940" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XX-2<img id="000941" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XX-3<img id="000942" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XX-4<img id="000943" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XX-5<img id="000944" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XX-6<img id="000945" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XX-7<img id="000946" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XX-8<img id="000947" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XX-9<img id="000948" he="63" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XX-10<img id="000949" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XX-11<img id="000950" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XX-12<img id="000951" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XX-13<img id="000952" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XX-14<img id="000953" he="64" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XX-15<img id="000954" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XX-16<img id="000955" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XX-17<img id="000956" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XX-18<img id="000957" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XX-19<img id="000958" he="61" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XX-20<img id="000959" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XX-21<img id="000960" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XX-22<img id="000961" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XX-23<img id="000962" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XX-24<img id="000963" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XX-25<img id="000964" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XX-26<img id="000965" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XX-27<img id="000966" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XX-28<img id="000967" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XX-29<img id="000968" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XX-30<img id="000969" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XX-31<img id="000970" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XX-32<img id="000971" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XX-33<img id="000972" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XX-34<img id="000973" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XX-35<img id="000974" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XX-36<img id="000975" he="65" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XX-37<img id="000976" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XX-38<img id="000977" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XX-39<img id="000978" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XX-40<img id="000979" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XX-41<img id="000980" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XX-42<img id="000981" he="62" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XX-43<img id="000982" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XX-44<img id="000983" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XX-45<img id="000984" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XX-46<img id="000985" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XX-47<img id="000986" he="60" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XX-48<img id="000987" he="57" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XX-49<img id="000988" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring. Table XX-50<img id="000989" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />* R2 and R3b are connected by (CH2) 3 to form a 5-membered ring.

0099<img id="000990" he="67" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="000991" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="000992" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="000993" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="000994" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="000995" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="000996" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="000997" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="000998" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="000999" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001000" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001001" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001002" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001003" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001004" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001005" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001006" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001007" he="109" wi="120" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />

0100<img id="001008" he="63" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001009" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001010" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001011" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001012" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001013" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001014" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001015" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001016" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001017" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001018" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001019" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001020" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001021" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001022" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001023" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001024" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001025" he="109" wi="120" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />

0101<img id="001026" he="61" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001027" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001028" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001029" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001030" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001031" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001032" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001033" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001034" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001035" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001036" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001037" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001038" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001039" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001040" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001041" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001042" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001043" he="109" wi="120" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />

0102<img id="001044" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001045" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001046" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001047" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001048" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001049" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001050" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001051" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001052" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001053" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001054" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001055" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001056" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001057" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001058" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001059" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001060" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001061" he="108" wi="120" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />

0103<img id="001062" he="62" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001063" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001064" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001065" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001066" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001067" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001068" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001069" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001070" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001071" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001072" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001073" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001074" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001075" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001076" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001077" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001078" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001079" he="108" wi="120" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />

0104<img id="001080" he="56" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001081" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001082" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001083" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001084" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001085" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001086" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001087" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001088" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001089" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001090" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001091" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001092" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001093" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001094" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001095" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001096" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001097" he="109" wi="120" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />

0105<img id="001098" he="62" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001099" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001100" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001101" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001102" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001103" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001104" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001105" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001106" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001107" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001108" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001109" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001110" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001111" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001112" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001113" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001114" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001115" he="108" wi="120" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />

0106<img id="001116" he="58" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001117" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001118" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001119" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001120" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001121" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001122" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001123" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001124" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001125" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001126" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001127" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001128" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001129" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001130" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001131" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001132" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001133" he="111" wi="120" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />

0107<img id="001134" he="66" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001135" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001136" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001137" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001138" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001139" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001140" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001141" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001142" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001143" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001144" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001145" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001146" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001147" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001148" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001149" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001150" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001151" he="108" wi="120" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />

0108<img id="001152" he="64" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001153" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001154" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001155" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001156" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001157" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001158" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001159" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001160" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001161" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001162" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001163" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001164" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001165" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001166" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001167" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001168" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001169" he="108" wi="120" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />

0109<img id="001170" he="63" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001171" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001172" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001173" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001174" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001175" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001176" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001177" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001178" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001179" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001180" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001181" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001182" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001183" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001184" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001185" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001186" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001187" he="108" wi="120" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />

0110<img id="001188" he="68" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001189" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001190" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001191" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001192" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001193" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001194" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001195" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001196" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001197" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001198" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001199" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001200" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001201" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001202" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001203" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001204" he="165" wi="121" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001205" he="110" wi="120" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />

0111Dose, administration, and use A sixth embodiment of the invention is directed to a composition for the treatment of any of the viral factors disclosed herein, wherein the composition is an excipient, carrier, diluent, And may include an acceptable medium as an agent selected from equivalent media and a obtainable salt thereof (acid or base addition salt) represented by Formula I, a hydrate, a solvate, and a crystalline form. Includes the intended compound. The formulation of the sixth embodiment is specifically listed in the above table, or the compound intended in any of the first, second, third, fourth, and fifth embodiments. Alternatively, it is contemplated that any of those exemplified herein can be included either alone or in combination with another compound of the invention.

0112The compounds of the present invention can be formulated in a wide variety of oral dosage forms and carriers. Oral administration can be in the form of tablets, coated tablets, hard and soft gelatin capsules, solutions, emulsions, syrups, or suspensions. Among other routes of administration, the compounds of the present invention are effective when administered by suppository administration. The most convenient mode of administration is generally oral, using a simple daily dosing regimen that can be adjusted according to the severity of the disease and the patient's response to antiviral drug therapy. The compounds of the invention, as well as their pharmaceutically acceptable salts, can be combined with one or more conventional excipients, carriers, or diluents in the form of pharmaceutical compositions and unit doses. The pharmaceutical composition and unit dosage form may contain conventional ingredients in conventional proportions with or without additional active compounds, and the unit dosage form is arbitrary, corresponding to the daily dose range of the subject to be used. It may contain a suitable effective amount of active ingredient. The pharmaceutical composition is a solid, semi-solid, powder, sustained release formulation such as tablets or filled capsules for oral use, or as a liquid such as a suspension, emulsion, or filled capsule, or for rectal or vaginal administration. It can be used in the form of suppositories. A typical preparation comprises from about 5% to about 95% active compound (w / w). The term "preparation" or "dosage form" is intended to include both solid and liquid formulations of the active compound, and those skilled in the art will appreciate that one active ingredient depends on the desired dose and pharmacokinetic parameters. Understand that it can be present in different preparations. The term "excipient" as used herein is used to prepare pharmaceutical compositions and is generally safe, non-toxic, and not biologically or otherwise undesirable. Refers to a compound and includes excipients that are acceptable for livestock use as well as pharmaceutical use in humans. The compounds of the invention can be administered alone, but generally as a mixture with one or more suitable pharmaceutical excipients, diluents, or carriers selected for the route of administration of interest and standard pharmaceutical practice. Be administered.

0113In addition, the "drug-acceptable salt" form of the active ingredient can first impart desirable pharmacodynamic properties to the active ingredient that was absent in the non-salt form, and further with respect to its therapeutic activity in the body. It can have a positive effect on the pharmacodynamics of the active ingredient. The phrase "pharmaceutically acceptable salt" of a compound as used herein means a salt that is pharmaceutically acceptable and has the desired pharmacological activity of the parent compound. Such salts include (1) acid addition salts, which are formed of inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitrate, phosphoric acid, or glycolic acid, pyruvate, lactic acid, malonic acid, Apple acid, maleic acid, fumaric acid, tartaric acid, citric acid, 3- (4-hydroxybenzoyl) benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethane-disulfonic acid, 2- Formed from organic acids such as hydroxyethane sulfonic acid, benzene sulfonic acid, 4-chlorobenzene sulfonic acid, 2-naphthalene sulfonic acid, 4-toluene sulfonic acid, camphor sulfonic acid, lauryl sulphate, gluconic acid, glutamic acid, salicylic acid, mucon acid, etc. , Or (2) a conjugated base of any of the inorganic acids listed above, Na +, K +, Mg2 +, Ca2 +, and NHgR'''4-g + (in the formula, R'''is C1- Contains a base addition salt formed of a conjugated base containing a cation component selected from (3 alkyl, where g is a number selected from 0, 1, 2, 3, or 4). It should be understood that all references to pharmaceutically acceptable salts include solvent-added forms (solvates) of identical acid addition salts or crystalline forms (polymorphs) as defined herein. Solid preparations include powders, tablets, pills, capsules, suppositories, and dispersible granules. The solid support can be one or more substances that can also act as diluents, flavoring agents, solubilizers, lubricants, suspending agents, binders, preservatives, tablet disintegrants, or encapsulating materials. In powder, the carrier is generally a finely divided solid that is a mixture with the finely divided active ingredient. In tablets, the active ingredient is generally mixed with a carrier having the required binding capacity in a suitable ratio and compressed to the desired shape and size. Suitable carriers include, but are not limited to, magnesium carbonate, magnesium stearate, talc, sugar, lactose, pectin, dextrin, starch, gelatin, tragant, methylcellulose, sodium carboxymethylcellulose, low melting point wax, cocoa butter and the like. .. In addition to the active ingredient, the solid preparation may include colorants, flavors, stabilizers, buffers, artificial and natural sweeteners, dispersants, thickeners, solubilizers and the like.

0114In addition, liquid preparations suitable for oral administration include liquid preparations containing emulsions, syrups, elixirs, and aqueous suspensions. These include solid preparations that are intended to be converted to liquid preparations shortly before use. Emulsions can be prepared in solution, for example in aqueous propylene glycol, or can contain emulsifiers such as lecithin, sorbitan monooleate, or acacia. Aqueous suspending agents are prepared by dispersing the micronized active ingredients in water with adhesive materials such as natural or synthetic rubbers, resins, methyl cellulose, sodium carboxymethyl cellulose, and other well-known suspending agents. be able to. The compounds of the present invention can be formulated for administration as suppositories. Low melting point waxes such as fatty acid glycerides or mixtures of cocoa butter are first melted and the active ingredients are homogeneously dispersed, for example by stirring. Then, the molten homogeneous mixture is poured into a mold of a convenient size, cooled, and solidified.

0115The compounds of the present invention can be formulated for intravaginal administration. Pessaries, tampons, creams, gels, pastes, foams, or sprays containing carriers in addition to the active ingredient as known to be suitable in the art. Suitable formulations, along with pharmaceutical carriers, diluents, and excipients, Remington: The Science and Practice of Pharmacy 1995, edited by EW It is described in Martin, Mack Publishing Company, 19th edition, Easton, Pennsylvania and is incorporated herein by reference. In addition, the compounds of the present invention can be encapsulated in liposomes such as those described in US Pat. Nos. 6,180,134, 5,192,549, 5,376,380, 6,060,080, 6,132,763, and each of these patents , Incorporated by reference. Skilled pharmaceutical scientists will modify the pharmaceuticals within the teachings herein to make a large number of pharmaceuticals for a particular route of administration without destabilizing the compositions of the invention or impairing their therapeutic activity. Can be provided.

0116Modifications of the Compound, for example to make it more soluble in water or in other vehicles, are readily accomplished with minor modifications (eg, salt formulations) that are well within the normal skill of the art. be able to. It is also well within the normal skill of the art to modify the route of administration and dosing regimen of a particular compound and control the pharmacokinetics of the compound in order to maximize efficacy in the patient. A seventh embodiment of the present invention is the following viral factors, hepatitis C virus, Westnile virus, yellow fever virus, dengue virus, rhinovirus, poliovirus, hepatitis A virus, bovine viral diarrhea virus. , And the use of the compound of formula I in the manufacture of drugs for the treatment of any condition as a result of infection by any one of the Japanese encephalitis viruses.

0117The term "drug" means a substance used in a method of treatment and / or prevention of a subject in need thereof, although the substance includes compositions, formulations, dosage forms, etc. containing compounds of formula I. , Not limited to these. A compound of the use of a compound of formula I in the manufacture of a drug for the treatment of any of the antiviral conditions disclosed herein in a seventh embodiment, alone or in the present invention. A compound contemplated in any of the first, second, third, fourth, fifth, and fifth embodiments, in combination with another compound of the invention, or specific in the table above. It is contemplated that it may be any of those listed in, or exemplified herein. The drug includes, but is not limited to, any one of the compositions contemplated by the sixth embodiment of the present invention. Eighth embodiment of the present invention is directed to a method of treatment and / or prevention in a subject in need thereof, wherein the method comprises administering to the subject a therapeutically effective amount of a compound of formula I. Including. The first aspect of the eighth embodiment is directed to a therapeutic and / or prophylactic method in a subject in need thereof, wherein the method is therapeutically effective in subjecting the subject to a range of compounds of formula I. It comprises the step of administering at least two or more different compounds in an amount.

0118A second aspect of the eighth embodiment is directed to a therapeutic and / or prophylactic method in a subject in need thereof, wherein the method, as an alternative or simultaneously, to the subject, a range of compounds represented by formula I. Includes the step of administering at least two compounds in therapeutically effective amounts within. Targets that require it are hepatitis C virus, Westnile virus, yellow fever virus, dengue virus, rhinovirus, poliovirus, hepatitis A virus, bovine viral diarrhea virus, or Japanese encephalitis virus, flavivirus family. Any of the viral factors disclosed herein, including, but not limited to, a virus or pestivirus or hepasivirus, or a viral factor that causes symptoms equivalent to or comparable to any of the viruses listed above. It is intended to have any condition as a result of virus infection.

0119The term "subject" means mammals, including but not limited to cattle, pigs, sheep, chickens, turkeys, buffaloes, llamas, ostriches, dogs, cats, and humans, preferably humans. is there. Any of the aspects of the first, second, and third embodiments, either alone or in combination with another compound of the invention, in the method of treating the subject of the sixth embodiment. It is contemplated that it can be either the compound intended in, or any of those specifically listed in the table above. As used herein, the term "therapeutically effective amount" means an amount that is required to alleviate the symptoms of a disease in an individual. The dose will be adjusted according to the individual's requirements in each particular case. The dose may include the severity of the disease being treated, the patient's age and overall health, other medications the patient is being treated for, the route of administration and form, and the preferences and experience of the healthcare professional involved. It can vary within a wide range of restrictions, depending on many factors. For oral administration, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, and 9.5 etc. per day A daily dose of about 0.1 to about 10 g, including all values in between, should be appropriate for monotherapy and / or combination therapy. The preferred daily dose is between about 0.5 and about 7.5 g per day, more preferably between 1.5 and about 6.0 g per day. Treatment generally begins with a large initial "loading dose" to rapidly reduce or eliminate the virus, then reduce the dose to a level sufficient to prevent the recovery of the infection. Those skilled in the art in the treatment of the diseases described herein will not rely on undue experimentation and personal knowledge, experience, and disclosure of this application for the compounds of the invention for a given disease and patient. The therapeutically effective amount of can be determined.

0120Therapeutic efficiency is not limited, but for serum proteins (eg albumin, coagulation factors, alkaline phosphatase, aminotransferases (eg, alanine transaminase, aspartate transaminase), 5'-nucleosidase, γ-glutaminyl transpeptidase, etc.) Liver function, including but not limited to protein levels, bilirubin synthesis, cholesterol synthesis, and bile acid synthesis, can be confirmed by testing liver metabolic function, including but not limited to carbohydrate metabolism, amino acid and ammonia metabolism. Alternatively, therapeutic efficacy can be monitored by measuring HCV-RNA. These tests allow for dose optimization. A third aspect of the eighth embodiment is directed to a therapeutic and / or prophylactic method in a subject in need thereof, wherein the method is directed to the subject in a therapeutically effective amount of a compound represented by formula I and therapeutically effective. The administration comprises the step of administering an amount of another antiviral agent, the administration being simultaneous or alternative. The time between alternative doses can range from 1 to 24 hours, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, It is understood to include all subranges in between, including 17, 18, 19, 20, 21, 22, and 23 hours. An example of "another antiviral agent" is HCV NS3 Protease Inhibitors (International Publication No. WO2008010921, International Publication No. WO2008010921, European Patent EP1881001, International Publication No. WO2007015824, International Publication No. WO2007014925, International Publication No. WO2007014926, International Publication No. WO2007014921, International Publication No. WO2007014920, International Publication WO2007014922, US Patent 2005267018, International Publication WO2005095403, International Publication WO2005037214, International Publication WO2004094452, US Patent 2003187018, International Publication WO200364456, International Publication WO2005028502 , And WO 2003006490), HCV NS5B Inhibitors (US Patent No. 2007275947, US Patent No. 20072759300, International Publication No. WO2007095269, International Publication No. WO2007092000, International Publication No. WO2007076034, International Publication No. WO200702602, US Patent No. 2005-98125, International Publication WO2006093801, US Patent 2006166964, International Publication WO2006065590, International Publication WO2006065335, US Patent 2006040927, US Patent 2006040890, International Publication WO2006020082, International Publication WO2006012078, International Publication WO2005123087 No., US Patent No. 2005154056, US Patent No. 2004229840, International Publication No. WO2004065367, International Publication No. WO2004003138, International Publication No. WO2004002977, International Publication No. WO2004002944, International Publication No. WO2004002940, International Publication No. WO2004000858, International Publication No. WO2003105770, International Publication No. WO2003010141, International Publication No. WO2002057425, International Publication No. WO2002057287, International Publication No. WO2005021568, International Publication No. WO2004041201, US Patent No. 20060293306, US Patent No. 20060194749, US Patent (See 20060241064, US Patent 6784166, International Publication WO2007088148, International Publication WO2007039142, International Publication WO2005103045, International Publication WO2007039145, International Publication WO2004096210, and International Publication WO2003037895), HCV NS4 Inhibitor (see WO2007070556 and WO2005067900), HCVNS5a inhibitors (see US Pat. No. 2006276511, WO2006120252, WO2006120251, WO2006100310, WO2006035061), Toll-like receptor agonists (see WO2007093901) ), And other inhibitors (see WO2004035571, WO2004014852, WO2004014313, WO2004009020, WO2003101993, WO2000006529). , Not limited to these.

0121A fourth aspect of the eighth embodiment targets a therapeutic method in a subject in need thereof, wherein the method, as an alternative or at the same time, a therapeutically effective amount of a compound represented by Formula I and another antiviral. Includes the step of administering the agent to the subject. The time between alternative doses can range from 1 to 24 hours, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, It is understood to include all subranges in between, including 17, 18, 19, 20, 21, 22, and 23 hours. A fifth aspect of the eighth embodiment is directed to a therapeutic and / or prophylactic method in a subject in need thereof, wherein the method comprises at least one compound in a therapeutically effective amount represented by Formula I and a therapeutically effective amount. It comprises the step of administering an amount of another antiviral agent, the administration being simultaneous or alternative. The time between alternative doses can range from 1 to 24 hours, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, It is understood to include all subranges in between, including 17, 18, 19, 20, 21, 22, and 23 hours.

0122A sixth aspect of the eighth embodiment is directed to a method of treatment in a subject in need thereof, wherein the method is alternative or simultaneously with at least one compound in a therapeutically effective amount represented by Formula I. Includes the step of administering the antiviral agent of the above to the subject. The time between alternative doses can range from 1 to 24 hours, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, It is understood to include all subranges in between, including 17, 18, 19, 20, 21, 22, and 23 hours. Other antiviral agents include interferon α, interferon β, pegulated interferon α, ribavirin, levovirin, viramidine, another nucleoside HCV polymerase inhibitor, HCV non-nucleoside polymerase inhibitor, HCV protease inhibitor, HCV helicase inhibitor, Alternatively, it is intended to include, but are not limited to, HCV fusion inhibitors. When the active compound or a derivative or salt thereof is administered in combination with another antiviral agent, the activity can be increased beyond the parent compound. If the treatment is a combination therapy, such administration can be simultaneous or continuous with that of the nucleoside derivative. Thus, as used herein, "co-administration" includes administration of the agent at the same or different time points. Administration of two or more drugs at the same time point is achieved by administration of a single formulation containing two or more active ingredients, or substantially simultaneous administration of two or more dosage forms having a single active drug. be able to.

0123It is understood that reference to treatment herein extends to prevention as well as treatment of existing conditions. In addition, the term "treatment" of HCV infection as used herein also includes the treatment or prevention of diseases or conditions associated with or transmitted by HCV infection or its clinical manifestations.

0124Preparation process A ninth embodiment of the invention is intended for a process for preparing a compound of formula I, comprising reacting a suitably substituted phosphorochloridate compound 4 with a nucleoside analog 5.<img id="001206" he="30" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />In the formula, substituents R1, R2, R3a, R3b, R4, R5, X, Y, R6, and bases have their meanings disclosed in the section of embodiments for carrying out the invention, where X'is. , Cl, Br, I, tosylate, mesylate, trifluoroacetate, trifluorosulfonate, pentafluorophenoxide, p-NO2-phenoxide, or Advanced Organic Chemistry by March, These are leaving groups such as other commonly used leaving groups disclosed in the Fourth Edition. Eleasing groups and methods that can be used to generate the formation of phosphoramidate nucleoside conjugates are found in US Pat. No. 20060142238 and WO2007095269. Preferably, the leaving group is Cl. The reaction is carried out in an aprotic anhydrous solvent such as tetrahydrofuran, dioxane, or both tetrahydrofuran and dioxane, or any functional equivalent thereof, with tetrahydrofuran being the preferred solvent. The reaction typically begins in the temperature range of -78 ° C to 40 ° C, with a preferred reaction temperature between 0 ° C and room temperature. First, the nucleoside is a base such as N-methylimidazole, colidin, pyridine, 2,6-lutidine, 2,6-tBu-pyridine (5 to 12 equivalents), a tertiary amine base such as triethylamine or diisopropylethylamine, or tBuMgCl, Stir with alkyl Grignard reagents such as tBuMgBr, MeMgCl, MeMgBr. Phosphorochloridate (3-10 eq) is dissolved in the reaction solvent and added to the mixture of nucleosides and bases. The reaction is then stirred at a temperature between room temperature and 40 ° C. for a period of 30 minutes to 24 hours, with the preferred reaction temperature being room temperature for 24 hours. The solvent is removed from the reaction mixture and the product is purified by silica gel chromatography.

0125A tenth embodiment of the present invention is directed to a product obtained by a process comprising the step of reacting a suitably substituted phosphorochloridate compound 4 with a nucleoside analog 5.<img id="001207" he="30" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />In the formula, substituents R1, R2, R3a, R3b, R4, R5, X, Y, R6, X', and bases have their meanings disclosed in the section of embodiments for carrying out the invention. The reaction can be carried out in an aprotic anhydrous solvent or in other suitable solvents such as tetrahydrofuran, dioxane, or a mixture of tetrahydrofuran and dioxane, with tetrahydrofuran being the preferred solvent. The reaction typically begins in the temperature range of -78 ° C to 40 ° C, with a preferred reaction temperature between 0 ° C and room temperature. First, the nucleoside is stirred with a base (5-12 equivalents) such as N-methylimidazole, a tertiary amine base, or t-butyl magnesium chloride. Phosphoramidite (3-10 equivalents) (or the preferred "phosphoro- (leaving group) -date")) is dissolved in the reaction solvent and added to the mixture of nucleosides and bases. The reaction is then stirred at a temperature between room temperature and 40 ° C. for a period of 30 minutes to 24 hours, with the preferred reaction temperature being room temperature for 24 hours. The solvent is removed from the reaction mixture and the product is purified by silica gel chromatography.

0126Compounds and preparations The phosphoramidate compounds of the present invention can be prepared by condensing the nucleoside analog 5 with a preferably substituted phosphorochloridate compound 4 (Scheme 1). Nucleoside analogs shall be prepared by conventional procedures disclosed in any one of US Publications 2005/0009737, 2006/0199783, 2006/0122146, and 2007/0197463. And each of those applications is incorporated by reference in its entirety. The disclosed 1H-NMR values were recorded on a Varian AS-400 instrument. Mass spectrum data was obtained using either the Micromass-Quattromicro API or Waters Acquity. Thus, by way of example only, a preferably substituted phenol is reacted with phosphorus oxychloride (1) to give aryloxyphosphologi chloride 2 (see Example 1), followed by the presence of TEA. Treatment with an acid addition salt of the α-amino acid ester can give aryloxyphosphorochloridate 4. This arylalkoxy-amino acid phosphoramidate is reacted with a nucleoside analog to provide product I (for procedures, eg, C. McGuigan et al. Antiviral Res. 1992 17: 311-321, D. Curley. See et al. Antiviral Res. 1990 14: 345-356, McGuigan et al. Antiviral Chem. Chemother 1990 1 (2): 107-113).

0127<img id="001208" he="95" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />Preparation of the nucleoside phosphoramidate requires reaction with a nucleoside containing the free 5'-hydroxyl moiety of the appropriately substituted phosphorochloridate. In the presence of only one hydroxyl group, the preparation of phosphoramidate usually proceeds well when the phosphorochloridate is reacted with the desired nucleoside. If the nucleoside contains more than one free hydroxyl group, it may be necessary to prepare a properly protected nucleoside. Cyril, acetonide, or other alcohol protecting groups known in the art may undertake protection of the sugar moiety. For protection of nucleoside bases, protection of free amino groups may require an amidine protection strategy. Condensation of phosphorochloridates can be performed on unprotected nucleosides. Since the 5'-OH group of the nucleoside is not as disturbed as the 3'-OH group, selective phosphoramidateization under carefully controlled conditions is possible. After condensing to form a protected phosphoramidate nucleoside, deprotection to obtain a free phosphoramidate nucleoside can be performed using standard protocols for nucleic acid chemistry. In many cases, the desired product can be easily separated from the starting material using silica gel column chromatography. The synthetic scheme is summarized in Scheme 1. Further understanding of the disclosed embodiments is obtained by considering the following examples, which are intended to be exemplary only and are not intended to limit the disclosed invention.

0128Example 1 Basic procedure for the preparation of phosphorodichloridates<img id="001209" he="29" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />A solution of the appropriate phenol R1-OH (1 eq) and triethylamine (1 eq) in anhydrous ether was added dropwise to a stirred solution of trichloride 1 (1 eq) under nitrogen over 3 hours at 0 ° C. The temperature was then warmed to room temperature and the reaction was stirred overnight. The triethylamine salt was quickly removed by suction filtration and the filtrate was concentrated to dryness in vacuo to give 2 as an oil, which was used without further purification.

0129Example 2 Basic steps for the preparation of phosphorochloridates<img id="001210" he="38" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />A solution of triethylamine (2 eq) in anhydrous dichloromethane is vigorously stirred at -78 ° C for 30-120 minutes with aryloxy-phosphodichloride 2 (1 eq) in anhydrous dichloromethane and a suitable amino ester. It was added dropwise to 3 (1 equivalent) of the solution. Then, the reaction temperature was warmed to room temperature, and the mixture was stirred overnight. The solvent was removed. The residue was washed with ethyl ether, filtered and the filtrate dried under reduced pressure to give 4.

0130Example 3 Basic steps for nucleoside phosphoramidate derivatives<img id="001211" he="38" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />A mixture of nucleoside 5 (1 equivalent) and N-methylimidazole (8 equivalents) in anhydrous THF with vigorous stirring of a suitable solution of phosphorochloridate 4 (6.5 equivalents) in anhydrous tetrahydrofuran (THF) at room temperature. And the reaction mixture was stirred overnight. The solvent was removed in vacuo and the crude was purified by column chromatography and / or thin layer chromatography for preparation to give I.

0131Example 4 Preparation of 2'-deoxy-2'-fluoro-2'-C-methyluridine<img id="001212" he="59" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />2'-deoxy-2'-fluoro-2'-C-methylcytidine (1.0 g, 1 eq) (Clark, J., et al., J. Med. Chem., 2005, 48, 5504-5508) was dissolved in 10 ml anhydrous pyridine and concentrated to dryness in vacuo. The resulting syrup was dissolved in 20 ml anhydrous pyridine under nitrogen and cooled to 0 ° C. with stirring. The brown solution was treated with benzoyl chloride (1.63 g, 3 eq) instills over 10 minutes. The ice bath was removed and stirring was continued for 1.5 hours, which showed thin layer chromatography (TLC) no remaining starting material. The reaction was stopped by the addition of water (0.5 ml) and concentrated to dryness. The residue was dissolved in 50 mL of dichloromethane (DCM) and washed with saturated aqueous LVDS3 solution and H2O. The organic phase is dried over NaSO4, filtered, concentrated to dryness and N4,3', 5'-tribenzoyl-2'-deoxy-2'-fluoro-2'-C-methylcytidine (2.0 g, yield). Rate: 91%) was obtained. N4,3', 5'-tribenzoyl-2'-deoxy-2'-fluoro-2'-C-methylcytidine (2.0 g, 1 eq) was refluxed overnight in 80% hydrous AcOH. After cooling to room temperature (15 ° C), most of the product settled and then filtered through a sintered funnel. The white precipitate was washed with water and co-evaporated with toluene to give a white solid. The filtrate was concentrated and co-evaporated with toluene to give additional product and washed with water to give a white solid. The two batches of white solid were combined to give 1.50 g of 3', 5'-dibenzoyl-2'-deoxy-2'-fluoro-2'-C-methyluridine (yield: 91%). Saturated ammonia in MeOH (20 mL) in a solution of 3', 5'-dibenzoyl-2'-deoxy-2'-fluoro-2'-C-methyluridine (1.5 g, 1 eq) in MeOH (10 mL) Was added to the solution of. The reaction mixture was stirred at 0 ° C. for 30 minutes and then slowly warmed to room temperature. After stirring the reaction mixture for an additional 18 hours, the reaction mixture was evaporated under reduced pressure to give a residue and purified by column chromatography to give the pure compound 2'-deoxy-2'-fluoro-2'-C-methyluridine. Obtained (500 mg, yield: 60%).

0132Example 5 Preparation of 2'-deoxy-2'-fluoro-2'-C-methyluridine 5'-(phenylmethoxy-alanyl phosphate)<img id="001213" he="33" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />Phenylmethoxyalaninyl phosphorochloridet (1 g, 6.5 eq) dissolved in 3 mL of THF was added to 2'-deoxy-2'-fluoro-2'-C-methyluridine (0.15 g, 1) in 3 mL of THF. Equivalent) and N-methylimidazole (0.3 g, 8 eq) were added to the mixture at room temperature with vigorous stirring, after which the reaction was stirred overnight. The solvent was removed by reduced pressure. The resulting crude product was dissolved in methanol and purified by preparative HPLC on a 25 × 30 × 2 mm column of YMC using a water / acetonitrile gradient elution transfer layer. Acetonitrile and water were removed under reduced pressure to give the desired product (50.1 mg, 15.6%). 1H NMR (DMSO-d6) δ1.20-1.27 (m, 6H), 3.58 (d, J = 16.0Hz, 3H), 3.75-3.92 (m, 2H), 4.015-4.379 (m, 2H), 5.54 (t) , J = 10.2Hz, 1H), 5.83-5.91 (m, 1H), 6.00-6.16 (m, 1H), 7.18 (d, J = 8.0Hz, 2H), 7.22 (s, 1H), 7.35 (t, J = 4.4Hz, 2H), 7.55 (s, 1H), 11.52 (s, 1H); MS, m / e502 (M + 1) +.

0133Example 6 Preparation of 2'-deoxy-2'-fluoro-2'-C-methyluridine 5'-(phenylmethoxy-valyl phosphate)<img id="001214" he="36" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />Phenylmethoxy-valylphosphorochloridate (0.6 g, 3.6 eq) dissolved in 3 mL of THF was added to 2'-deoxy-2'-fluoro-2'-C-methyluridine (0.15 g) in 3 Ml of THF. , 1 eq) and N-methylimidazole (0.44 g, 9 eq) were added with vigorous stirring at room temperature, after which the reaction was stirred overnight. The solvent was removed by reduced pressure. The resulting crude product was dissolved in methanol and purified by preparative HPLC on a 25 × 30 × 2 mm column of YMC using a water / acetonitrile gradient elution transfer layer. Acetonitrile and water were removed under reduced pressure to give the desired product (60 mg, 20%). 1H NMR (DMSO-d6) δ0.74-0.847 (m, 6H), 1.20-1.28 (m, 3H), 1.89-1.92 (m, 1H), 3.50-3.54 (m, 1H), 3.58 (d, J = 10.4Hz, 3H), 3.72-3.95 (m, 1H), 4.03-4.05 (m, 1H), 4.23-4.43 (m, 2H), 5.56 (t, J = 16.0Hz, 1H), 5.85-5.92 (m) , 1H), 6.01-6.07 (m, 1H), 7.16-7.21 (m, 3H), 7.37 (t, J = 8Hz, 2H), 7.55-7.60 (m, 1H), 11.52 (s, 1H); MS , M / e530 (M + 1) +.

0134Example 7 Preparation of 2'-deoxy-2'-fluoro-2'-C-methyluridine 5'-(4-bromophenylmethoxy-valyl phosphate)<img id="001215" he="39" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />4-Bromophenylmethoxy-valylphosphorochloridate (1 g, 3.4 eq) dissolved in 3 mL of THF was added to 2'-deoxy-2'-fluoro-2'-C-methyluridine (0.2) in 3 mL of THF. It was added to a mixture of g, 1 eq) and N-methylimidazole (0.35 g, 6 eq) with vigorous stirring at room temperature, after which the reaction was stirred overnight. The solvent was removed by reduced pressure. The resulting crude product was dissolved in methanol and purified by preparative HPLC on a 25 × 30 × 2 mm column of YMC using a water / acetonitrile gradient elution transfer layer. Acetonitrile and water were removed under reduced pressure to give the desired product (120 mg, 26%). 1H NMR (DMSO-d6) δ0.72-0.82 (m, 6H), 1.19-1.26 (m, 3H), 1.86-1.92 (m, 1H), 3.48-3.50 (m, 1H), 3.56 (d, J = 12.0Hz, 3H), 3.72-3.89 (m, 1H), 3.96-4.03 (m, 1H), 4.22-4.37 (m, 2H), 5.54-5.60 (m, 1H), 5.85-5.91 (m, 1H) , 5.98-6.13 (m, 1H), 7.15 (d, J = 8.0Hz, 2H), 7.49-7.56 (m, 3H), 11.53 (s, 1H); MS, m / e608 (M + 1) +.

0135Example 8 Preparation of 2'-deoxy-2'-fluoro-2'-C-methyluridine 5'-(4-bromophenylmethoxy-alanyl phosphate)<img id="001216" he="34" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />4-Bromophenylmethoxy-alanyl phosphorochloridate (0.6 g, 5 eq) dissolved in 3 mL of THF was added to 2'-deoxy-2'-fluoro-2'-C-methyluridine in 3 mL of THF. A mixture of (0.15 g, 1 eq) and N-methylimidazole (0.3 g, 7.8 eq) was added with vigorous stirring at room temperature, after which the reaction was stirred overnight. The solvent was removed by reduced pressure. The resulting crude product was dissolved in methanol and purified by preparative HPLC on a 25 × 30 × 2 mm column of YMC using a water / acetonitrile gradient elution transfer layer. Acetonitrile and water were removed under reduced pressure to give the desired product (40 mg, 12%). 1H NMR (DMSO-d6) δ1.20-1.26 (m, 6H), 3.57 (d, J = 2.8Hz, 3H), 3.84 (s, 1H), 3.97-4.03 (m, 1H), 4.21-4.25 (m) , 1H), 4.33-4.37 (m, 2H), 5.54-5.60 (m, 1H), 5.83-5.89 (m, 1H), 5.98-6.19 (m, 1H), 7.16 (t, J = 10.2Hz, 2H) ), 7.52-7.57 (m, 3H), 11.52 (s, 1H); MS, m / e580 (M + 1) +.

0136Example 9 Preparation of N4- (N, N-dimethylformamidinyl) -2'-deoxy-2'-fluoro-2'-C-methylcytidine<img id="001217" he="29" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />2'-deoxy-2'-fluoro-2'-C-methylcytidine (500 mg, 1.9 mmol) was stirred with dimethylformamide dimethylacetal in DMF (10 mL). The resulting mixture was stirred overnight at room temperature. After removal of the solvent, the crude product was used in the next step without further purification.

0137Example 10 Preparation of 2'-deoxy-2'-fluoro-2'-C-methylcytidine 5'-(phenylmethoxy-alanyl phosphate)<img id="001218" he="29" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />Phenylmethoxyalaninyl phosphorochloridate (0.6 g, 6 eq) dissolved in 3 mL of THF was added to N4- (N, N-dimethylformamidinyl) -2'-deoxy-2'- in 3 mL of THF. A mixture of fluoro-2'-C-methylcitidine (0.15 g, 1 eq) and N-methylimidazole (0.3 g, 7.8 eq) was added with vigorous stirring at room temperature, after which the reaction was stirred overnight. The solvent was removed by reduced pressure. The resulting crude product was dissolved in methanol and purified by preparative HPLC on a 25 × 30 × 2 mm column of YMC using a water / acetonitrile gradient elution transfer layer. Acetonitrile and water were removed under reduced pressure to give the desired product (62 mg, 20.6%). 1H NMR (DMSO-d6) δ1.16 (d, J = 23.2Hz, 3H), 1.22 (d, J = 7.2Hz, 3H), 3.56 (s, 3H), 3.69-3.75 (d, J = 25.6Hz, 1H), 3.82-3.86 (m, 1H), 3.96-3.98 (m, 1H), 4.21-4.34 (m, 2H), 5.68 (d, J = 7.2Hz, 1H), 5.75-5.77 (m, 1H) , 6.07-6.16 (m, 1H), 7.15-7.19 (m, 3H), 7.2 (d, J = 9.2Hz, 2H), 7.39 (t, J = 7.8Hz, 2H), 7.48 (d, J = 9.2) Hz, 1H); MS, m / e501 (M + 1) +.

0138Example 11 Preparation of 2'-deoxy-2'-fluoro-2'-C-methylcytidine 5'-(4-bromophenylmethoxy-valyl phosphate)<img id="001219" he="35" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />4-Bromophenylmethoxy-valylphosphorochloridate (1.0 g, 3.4 eq) dissolved in 3 mL of THF was added to N4- (N, N-dimethylformamidinyl) -2'-deoxy- in 3 mL of THF. Add to a mixture of 2'-fluoro-2'-C-methylcitidine (0.2 g, 1 eq) and N-methylimidazole (0.35 g, 6 eq) with vigorous stirring at room temperature, followed by overnight stirring of the reaction. did. The solvent was removed by reduced pressure. The resulting crude product was dissolved in methanol and purified by preparative HPLC on a 25 × 30 × 2 mm column of YMC using a water / acetonitrile gradient elution transfer layer. Acetonitrile and water were removed under reduced pressure to give the desired product as a white solid (59 mg, 13%). 1H NMR (DMSO-d6) δ0.74-0.83 (m, 6H), 1.12-1.20 (m, 3H), 1.89-1.92 (m, 1H), 3.49-3.51 (m, 1H), 3.55 (s, 3H) , 3.59-3.68 (m, 1H), 3.72-.383 (m, 1H), 4.21-4.39 (m, 2H), 5.70-5.72 (m, 1H), 5.76-5.83 (m, 1H), 6.04-6.16 (m, 1H), 7.15 (d, J = 13.0Hz, 2H), 7.26 (s, 1H), 7.33 (s, 1H), 7.46-7.55 (m, 1H), 7.56 (d, J = 4.4Hz, 2H); MS, m / e607 (M + 1) +.

0139Example 12 Preparation of 2'-deoxy-2'-fluoro-2'-C-methylcytidine 5'-(phenylmethoxy-valyl phosphate)<img id="001220" he="33" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />Phenylmethoxyvalyl phosphorochloridate (0.6 g, 6 eq) dissolved in 3 mL of THF was added to N4- (N, N-dimethylformamidinyl) -2'-deoxy-2'-fluoro in 3 mL of THF. A mixture of -2'-C-methylcitidine (0.15 g, 1 eq) and N-methylimidazole (0.3 g, 7.8 eq) was added with vigorous stirring at room temperature, after which the reaction was stirred overnight. The solvent was removed by reduced pressure. The resulting crude product was dissolved in methanol using a water / acetonitrile gradient elution transfer layer and purified by preparative HPLC on a YMC 25 × 30 × 2 mm column. Acetonitrile and water were removed under reduced pressure to give the desired product as a white solid (86 mg, 42.9%). 1H NMR (DMSO-d6) δ0.72-0.80 (m, 6H), 1.09-1.18 (m, 3H), 1.87-1.92 (m, 1H), 3.47-3.51 (m, 1H), 3.58 (s, 3H) , 3.71-3.75 (m, 1H), 3.97 (t, J = 11.2Hz, 1H), 4.22-4.37 (m, 2H), 5.70 (d, J = 8.0Hz, 1H), 5.76-5.84 (m, 1H) ), 6.01-6.15 (m, 1H), 7.13-7.18 (m, 3H), 7.27 (s, 2H), 7.34 (d, J = 4.0Hz, 2H), 7.46-7.50 (m, 1H); MS, m / e529 (M + 1) +.

0140Example Examples 13-54 and 56-66 are prepared using a procedure similar to that described for Examples 5-8. Example numbers, compound identification, and NMR / MS details are shown below.<img id="001221" he="32" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />

0141<img id="001222" he="125" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001223" he="204" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001224" he="204" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001225" he="202" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001226" he="203" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001227" he="207" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001228" he="201" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001229" he="203" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001230" he="202" wi="158" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001231" he="203" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001232" he="203" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001233" he="221" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001234" he="114" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />

0142Purification procedure by preparatory HPLC The crude product was dissolved in methanol. The injection volume of these solutions was 5 mL. The preparative HPLC system included two sets of Gilson 306 pumps, a Gilson 156 UV / Vis detector, a Gilson 215 injector and an automatic preparative device, along with management software. A Ymc 25 × 30 × 2 mm column was used. The mobile phases were HPLC grade water (A) and HPLC grade acetonitrile (B). Fractions were collected in 100 * 15 mm glass tubes. The HPLC gradient is shown in Table 1. Once the gradient was selected, an acetonitrile solution was injected into the HPLC system and then fractions were collected according to UV peaks. After separation, each glass tube was subjected to an MS (mass spectrometry) test to collect the desired compound. The target MS fractions were combined in a well weighted flask. Most of the acetonitrile was removed under reduced pressure and the remaining solution was lyophilized to give the desired compound.<img id="001235" he="31" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />

0143Preparation of Example 66 scheme<img id="001236" he="112" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />

0144Preparation of compound (b) A solution of compound a (1 g, 2.69 mmol) in anhydrous THF (30 mL) was added dropwise to a solution of LiAl (OBu-t) 3H in 1 M THF (2.69 mL, 2.69 mmol) at -20 ° C. The reaction mixture was stirred for 2-3 hours at the same temperature. EtOAc (100 mL) followed by saturated NH4Cl solution (10 mL) was added and the reaction mixture was slowly warmed to room temperature. The reaction mixture was extracted with EtOAc and washed with 1N HCl and water. The combined organic phases were evaporated to give 0.8 g of crude compound b as a clear oil, which was used directly in the next reaction. Preparation of compound (d) Add DEAD (1.8 mL) to a solution of compound b (0.8 g, 2.1 mmol), compound c (0.45 g, 2.5 mmol), and Ph3P (0.56 g, 2.1 mmol) in anhydrous THF (20 mL) under a nitrogen atmosphere. Added. The reaction mixture was stirred at room temperature overnight. The reaction solution was concentrated under reduced pressure. The residue was separated by preparative layer chromatography (hexane: EtOAc = 3: 1) to give crude compound d (0.8 g). Crude compound d was used in the next step without further purification. Preparation of compound (e) Compound d (0.8 g, 1.57 mmol) was dissolved in THF (2 mL) and ammonia-saturated THF (5 mL) and then added to the solution. The reaction mixture was heated at 90 ° C overnight. After 18 hours, the solution was cooled to room temperature with ice water, then the solvent was removed under reduced pressure and the residue was purified on a column to give compound e (0.75 g) for the next step. Preparation of compound (f) Compound e (0.5 g, 1.01 mmol) was dissolved in methanol (2 mL) and ammonia-saturated methanol (5 mL) and then added to the solution. The reaction mixture was stirred at room temperature overnight. After 18 hours, the solvent was removed under reduced pressure and the residue was purified on a column to give crude compound f (0.15 g) for the next step. Preparation of compound (i) A solution of triethylamine (1.07 g, 10.6 mmol) in dichloromethane (15 mL) to a solution of compound g (1.16 g, 5.3 mmol) and compound h (1.31 g, 5.3 mmol) in dichloromethane (10 mL), -78. The solution was added dropwise over 2 hours with vigorous stirring at ° C. After completion of the addition, the reaction temperature was gradually warmed to room temperature and stirred overnight. The solvent was then removed under vacuum, 20 mL of anhydrous ether was added, the precipitated salt was filtered and the precipitate was washed with ether. The combined organic phases were concentrated to give compound i (1.0 g) a colorless oil.

0145Preparation of compound 66 To a solution of compound j (0.1 g, 0.35 mmol) dissolved in 10 mL anhydrous THF, 0.4 g NMI was added with stirring until the solution became clear, and compound i (0.8 g, 2.89 mmol) in 10 mL THF was added. Was added dropwise, and the mixture was stirred overnight at room temperature. The purity and identification of the compounds was confirmed by LCMS. The solvent was evaporated and purified by preparative HPLC to give 66 (25 mg, yield: 13.6%). 1H NMR (DMSO-d6) δ1.08 (d, J = 22.8Hz, 3H), 1.17-1.24 (m, 3H), 3.50-3.52 (m, 3H), 3.78-3.83 (m, 1H), 4.10- 4.13 (m, 1H), 4.24-4.44 (m, 2H), 5.85-5.92 (m, 1H), 6.01-6.11 (m, 1H), 6.2.-6.27 (m, 1H), 7.08-7.19 (m, 4H), 7.31-7.38 (m, 3H), 8.15 (s, 1H), 8.26 (s, 1H); MS, m / e525 (M + 1) +. Example numbers 67-74 identified below were prepared using a procedure similar to that disclosed for Example 66 above.<img id="001237" he="41" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001238" he="68" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001239" he="208" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001240" he="81" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />

0146Examples 75-80 are prepared using a procedure similar to that disclosed for Example 66 above.<img id="001241" he="43" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001242" he="94" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />

0147Example 81 Some exemplified compounds were obtained as a mixture of diastereomers due to their chirality with phosphorus. Diastereomers were separated on a Chilarpak-AS-H (2 x 25 cm) column under Supercritical Fluid Chromatography (SFC) conditions using 20% methanol in carbon dioxide as the solvent. Absolute stereochemistry of the P-chiral center of the diastereomer was not determined. However, chromatographic division of these two diastereomers provides isomers characterized as rapidly elution and slow elution isomers. Some examples are shown below.<img id="001243" he="123" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />

0148Example 82 HCV Replicon Assay. HCV Replicon RNA-containing Huh7 cells (cloned A cells-Apath, LLC, St. Louis, Mo.) Have 10% bovine fetal serum, 4 mM L-glutamine and 1 mM sodium pyruvate, 1 × non-essential amino acids, and Exponential growth was maintained in Dalvecco modified Eagle's medium (high glucose) containing G418 (1,000 μg / ml). The antiviral assay was performed in the same medium except G418. Cells were seeded on 96-well plates with 1,500 cells per well and test compound was added immediately after seeding. The culture time was 4 days. At the end of the culture step, whole cell RNA was isolated (RNeasy96 kit, Qiagen). Replicon RNA and internal standards (TaqMan rRNA standard reagents, Applied Biosystems) were amplified with a single-step multiplex RT-PCR protocol as recommended by the manufacturer. HCV primers and probes are Primer Express software (Applied Designed with Biosystems) and targeted to highly conserved 5'-Untranslated Region (UTR) sequences (Sense, 5'-AGCCATGGCGTTAGTA (T) GAGTGT-3', and Antisense, 5'-TTCCGCAGACCACTATGG -3', probe, 5'-FAM-CCTCCAGGACCCCCCCTCCC-TAMRA-3'). To represent the antiviral effect of the compound, the threshold RT-PCR cycle of the test compound was subtracted from the mean threshold RT-PCR cycle of the non-drug control (ΔCtHCV). ΔCt of 3.3 is equal to the 1-logarithm 10 decrement at the Replicon RNA level (equal to 90% effective concentration [EC90]). The cytotoxicity of the test compound could also be expressed by producing ΔCtrRNA values. The level of HCV RNA is then normalized for rRNA levels and a ΔΔCt specificity parameter is introduced that is calibrated for non-drug controls (ΔCtHCV ΔCtrRNA).

0149<img id="001244" he="171" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001245" he="192" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001246" he="207" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="001247" he="52" wi="159" file="JP5774749B2_D0001.tif" img-format="tif" img-content="drawing" />

0150The entire contents of No. 60 / 909,315 filed March 30, 2007, No. 60 / 982,309 filed October 24, 2007, and No. 12 / 053,015 filed March 21, 2008 are disclosed in this disclosure. Is incorporated herein by reference to the extent necessary to complement and / or correct any errors. In addition, the patented and non-patent references disclosed herein are incorporated by reference. If the incorporated patent and non-patent references contain terms that contradict the terms disclosed in any one of the two provisional applications or the text of the present application, the meaning of the terms contained in the text of the present application and the two provisional applications. Is prioritized, but the overall meaning of the incorporated subject is not lost.