Nucleoside phosphoramidate prodrugs

> COMPOUND, ITS STEREOISOMER, SALT, HYDRATE, SOLVATE, OR CRYSTALLINE FORM THEREOF AND PROCESS FOR THE PREPARATION AND USE OF THE SAME, COMPOSITION FOR TREATMENT AND/OR PROPHYLAXIS OF ANY VIRAL AGENTS, USE OF COMPOUND, METHOD OF

TREAT INDIVIDUAL

Field of Invention

The present invention refers to phosphoramidate nucleosides and their use as agents for the treatment of viral diseases. These compounds are inhibitors of RNA-dependent RNA viral replication and are useful as inhibitors of HCV NS5B polymerase, as inhibitors of HCV replication, and for the treatment of hepatitis C in mammals. The invention presents new chemical compounds and the use of these compounds alone or in combination with 15 other antiviral agents for the treatment of HCV infection.

Fundamentals

The hepatitis C virus (HCV) is a serious health problem that causes chronic liver diseases, such as cirrhosis and hepatocellular carcinoma, in a significant number of infected individuals estimated at 2-15% of the world's population. There are an estimated 4.5 million people infected in the United States, according to the US Center for Disease Control. According to the 25 World Health Organization, there are more than 200 million people infected worldwide, with at least 3 to 4 million people being infected each year. Once infected, about 20% of people clear the virus, however, the rest can harbor HCV for the rest of their lives.

Between ten and twenty percent of infected individuals

2/967 chronically eventually develop liver cirrhosis or cancer. The viral disease is transmitted parenterally by contaminated blood and blood products, contaminated needles or sexually and vertically from infected mothers or carrier mothers to their offspring. Current treatments for HCV infection, which are restricted to immunotherapy with recombinant interferon-α alone or in combination with the nucleoside analog ribavirin, are of limited clinical benefit. In addition, there is no established vaccine for HCV. Consequently, there is a great need to improve therapeutic agents that effectively combat chronic HCV infection.

The HCV virion is a positive-strand RNA virus with a single oligoribonucleotide genomic sequence of about 9,600 bases that encodes a polyprotein of about 3,010 amino acids. The protein products of the HCV gene consist of structural proteins C, E1 and E2 and the non-structural proteins NS2, NS3, NS4A and NS4B and NS5A and NS5B. It is believed that non-structural proteins (NS) provide catalytic mechanisms for viral replication. The NS3 protease releases NS5B, the polyprotein chain-dependent RNA polymerase. HCV NS5B polymerase is required for the synthesis of a double-stranded RNA from a single-stranded viral RNA, which serves as a template in the HCV replication cycle. Therefore, the NS5B polymerase is considered an essential component of the compound in the HCV replication complex (K. Ishi, et al, Heptology, 1999, 29: 1227-1235; V. Lohmann, et al., Virology, 1998, 249: 108118). Inhibition of HCV NS5B polymerase prevents formation

3/967 of HCV double-stranded RNA and therefore constitutes an attractive method for the development of HCV-specific antiviral therapies.

HCV belongs to a much larger family of viruses that share many common characteristics.

Flaviviridae virus

The flaviviridae virus family that includes at least three different genera: pestivirus, which causes disease in pigs and cattle; flaviviruses, which are the first 10 causes of diseases, such as dengue and yellow fever; and hepacivirus, whose unique member is HCV. The flavivirus genus includes more than 68 members separated between groups based on serological relationship (Calisher et al., J. Gen. Virol, 1993,70,37-43). Clinical symptoms vary 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). Flaviviruses of global concern that are associated with human disease 20 include dengue hemorrhagic fever (DHF) virus, 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, NewEng. J. Med, 1988, 319, 64 1-643).

The genus pestivirus includes bovine viral diarrhea virus (BVDV), classical swine fever virus (VPSC, also called hog cholera virus) and ovine border disease virus (BDV) (Moennig, V. et al. Adv. Vir. Re: 1992, 41, 53-98). Pestivirus infections of 30 farm animals (cattle, pigs and sheep) cause significant economic losses worldwide. BVDV causes mucosal disease in cattle and is of significant economic importance to the livestock industry (Meyers, G. and Thiel, HJ, Advances in Virus Research, 1996, 47, 53-118; Moennig V. , 5 et al, Adv. Vir. Re: 1992, 41, 53-98). The human pestivirus has not been extensively characterized as the animal pestivirus. However, serological research indicates considerable exposure to the pestivirus in humans.

Pestiviruses and hepaciviruses are closely related to groups of viruses in the Flaviviridae family. Other closely related viruses in the family include GB-A virus, GB-A virus-like agents, GB-B virus, and GB-C virus (also called hepatitis G virus, HGV). The hepacivirus group (hepatitis C virus; HCV) is constituted 15 by a number of closely related, but genotypically different viruses that infect humans. There are at least 6 genotypes of HCV and more than 50 subtypes. Because of the similarities between pestivirus and hepacivirus, combined with the poor capacity of hepacivirus for efficient growth 20 in cell culture, the bovine viral diarrhea virus (BVD) is often used as a surrogate for the study of the HCV virus.

The genetic organization of pestivirus and hepacivirus is very similar. This positive-strand 25 RNA virus possesses a unique and large open reading frame (ORF) encoding all viral proteins required for viral replication. These proteins are expressed as a polyprotein that is co- and post-translationally processed by cellular proteinases and encoded in viruses 30 to produce the mature viral proteins. The proteins

5/967 viruses responsible for the replication of the RNA viral genome are located approximately at the carboxy terminus. Two-thirds of the ORF are called nonstructural (NS) proteins. The genetic organization and processing of polyproteins from the non-structural proteins of the ORF for pestiviruses and hepaciviruses are very similar. For both pestiviruses and hepaciviruses, the mature nonstructural (NS) proteins, in sequential order from the amino-terminus of the nonstructural protein coding region to the carboxy-terminus of the ORF, consist of P7, NS2, NS3, NS4A, NS4B, NS5A, and NS5B.

Pestivirus and hepacivirus NS proteins share sequence domains that are characteristic of specific protein functions. For example, the NS3 proteins of viruses in both groups possess major amino acid sequence characteristics of serine proteinases and helicases (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). In the same way, the NS5B proteins of pestivirus and hepacivirus possess typical characteristics of direct RNA polymerase RNA (Koonin, EV and Dolja, VV, Crir. Re: Biochem. Molec. Biol. 1993, 28, 375430).

The actual functions and roles of pestivirus and hepacivirus NS proteins in the virus life cycle are directly analogous. In both cases, the NS3 serine protease is responsible for all downstream proteolytic processing of polyprotein precursors for their position in the ORF (Wiskerchen and Collett, Virology, 1991, 184, 341

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350; Bartenschlager et al., J. Virol. 1993, 67, 3835-3844; Eckart et al. Biochem. Biophys. Re: Comm. 1993,192, 399406; Grakoui et al., J. Virol. 1993, 67, 2832-2843; Grakoui et al., Proc. Natl. Acad Sci. USA 1993, 90, 1058310587; Hijikata et al., J. Virol. 1993, 67, 4665-4675; Tome et al., J. Virol., 1993, 67, 4017-4026). The NS4A protein, in both cases, acts as a cofactor with the NS3 serine protease (Bartenschlager et al., J. Virol. 1994, 68, 5045-5055; Tome et al., J. Virol. 1994, 68, 3753-3760; Tome et al., J. Virol., 1997, 71:53 12-5322). The NS3 protein of both viruses also functions as a helicase (Kim et al., Biochem. Biophys. Re: 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 pestiviruses and hepaciviruses possess a directed 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. Re: Comm. 1997, 232, 231-235; Hagedorn, PCT WO 97/12033; Zhong et al, J. Med, 1998, 72, 9365 9369-).

Currently, there are few options for the treatment of individuals infected with the hepatitis C virus. The current approved therapeutic option has been the use of immunotherapy with recombinant interferon-alpha alone or in combination with nucleoside analog ribavirin. This therapy is limited in its clinical effectiveness and only 50% of treated patients respond to therapy. Therefore, it is necessary to develop more effective and innovative therapies that respond to the medical need posed by the infection of

HCV.

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A series of possible molecular targets for the development of antiviral drugs with direct action as therapeutic anti-HCV have already been identified, including, among others, NS2-NS3 autoprotease, N3 protease, 5 N3 helicase and NS5B polymerase. RNA-dependent RNA polymerase is absolutely essential for replication of the single-stranded, positive-sense, RNA genome and this enzyme has sparked great interest among medicinal chemists.

HCV NS5B inhibitors as possible therapies for HCV infection were discussed in: 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; Nor, ZJ. , et al., Current Opinion in Drug Discovery and Development, 2004, 7, 446-459; Beaulieu, PL , 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; Carrol, S., et al., 20 Infectious Disorders-Drug Targets, 2006, 6, 17-29. 0 potential for the emergence of HCV-resistant filaments and the need to identify agents with broad genotype coverage supports the need to continue efforts to identify new and more effective nucleoside 25 as HCV NS5B inhibitors.

Nucleoside inhibitors of NS5B polymerase can act both as a non-natural substrate that results in chain termination, or as a competitive inhibitor that competes with the binding of nucleotides by the polymerase. 30 To act as a chain terminator, the analog of

8/967 nucleoside must be taken up by the cell and converted in vivo to a triphosphate to compete for the nucleotide polymerase binding site. This triphosphate conversion is usually mediated by cellular kinases that confer additional structural requirements on a potential nucleoside polymerase inhibitor. Unfortunately, this limits direct evaluation of nucleosides as inhibitors of HCV replication to cell-based assays capable of in situ phosphorylation.

In some cases, the biological activity of a nucleoside is hampered by its poor substrate characteristics for one or more of the kinases required to convert it to the active triphosphate form. Monophosphate formation by a nucleoside kinase is usually seen as the rate-limiting step of three phosphorylation events. To circumvent the need for the initial phosphorylation step in the metabolism of a nucleoside to the active triphosphate analog, the preparation of stable phosphate prodrugs has been reported. Nucleoside phosphoramidate prodrugs appear to be precursors of the active nucleoside triphosphate and for inhibition of viral replication when administered to infected whole viral 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, EJ , et al., Nucleosides, Nucleotides and Nucleic Acids, 2001, 20, 1091-1098; Lee, WA, et al., Antimicrobial Agents and Chemotherapy, 2005, 49, 1898); US 2006/0241064; and WO 2007/095269.

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In addition, limiting the utility of nucleosides as viable therapeutic agents they can sometimes have poor pharmacokinetic and physicochemical properties. These poor properties can limit intestinal absorption of an agent and limit uptake by the target tissue or cell. To improve their properties, prodrugs of nucleosides were used. It has been shown that the preparation of phosphoramidate nucleosides increases the systemic absorption of nucleosides and, in addition, the phosphoramidate fraction of these pronucleotides is masked with neutral lipophilic groups to obtain a partition coefficient suitable to optimize uptake and transport into the cell by dramatically increasing the intracellular concentration of the nucleoside monophosphate analog relative to the administration of the parent nucleoside alone. Enzyme-mediated hydrolysis of the phosphate ester moiety produces a nucleoside monophosphate in which the rate-limiting initial phosphorylation is unnecessary.

SUMMARY OF THE INVENTION

The present invention refers to the new phosphoramidate prodrugs of nucleoside derivatives for the treatment of viral infections in mammals, which is a compound, its stereoisomers, salts (salts with addition of acid or base), hydrate, solvate, or crystalline form thereof, represented by the following structure:

R2 θ

<img file="BRPI0809654A2_D0001.tif" />

And^?

I

10/967 where (a) R¹ is hydrogen, n-alkyl; branched alkyl; cycloalkyl; or aryl, which includes, but is not limited to, phenyl or naphthyl, where phenyl or naphthyl is optionally substituted with at least one of Ci-6 alkyl, C2.6 alkenyl, C2-6 alkynyl, Ci-S alkoxy, F, Cl, Br, I, nitro, cyano, Ci-6 haloalkyl, -N(R¹')2, Ci-₆ acylamino, -NHSO₂Ci_₆rent, -SO₂N(R¹')2, COLOR¹, and -SO2Ci-₆ rent; (R¹' is independently hydrogen or alkyl, which includes, but is not limited to, C1-20 alkyl, C1-10 alkyl, or C1-6 alkyl, R¹ is -OR' or -NÍR¹')2);

(b) R² is hydrogen, C i-10 alkyl, R^3rd or R^3b and R²together they are (CH2)_n so as to form a cyclic ring that includes the adjacent atoms N and C, C(O) CR^3rdR^3bNHR¹, where n is 2 to 4 and R¹, R^3rd, and R^3b;

(c) R^3rd and R^3b are (i) independently selected from hydrogen, Ci-io alkyl, cycloalkyl, - (CH2) c (NR³') 2, Ci-6 hydroxyalkyl, -CH₂SH, - (CH₂) ₂Yes (O)_dMe, (CH₂)₃NHC(=NH)NH_2z (1H-indol-3-yl)methyl, (1H-imidazol-4yl)methyl, - (CH₂) _andCOLOR³, aryl and aryl Ci-3 alkyl, said aryl groups optionally substituted by a group selected from hydroxyl, Ci-10 alkyl, Ci-6 alkoxy, halogen, nitro and cyano; (ii) R^3rd and R^3b both are C₁₋ alkyl; (iii) R^3rd and R^3b together they are (CH2)f so as to form a spiro ring; (iv) R^3rd is hydrogen and R^3b and R² together they are (CH2)n so as to form a cyclic ring that includes the adjacent atoms N and C (v) R^3b is hydrogen and R^3rd and R²together they are (CH2)_n so as to form a cyclic ring that includes adjacent atoms N and C, where c is 1 to 6, déOa 2, eé0a3, f is 2 to 5, né2a4, and where R³ ' ê

11/967 regardless of hydrogen or Cx-₆ rent and R³ is -OR' or - N(R³')2); (vi) R^3rd is H and R^3b is H, CH3, CH₂CH₃, CH(CH₃)₂, CH₂CH(CH₃)₂, CH(CH₃) CH₂CH₃, CH₂Ph, CH₂-indole-3-yl, ch₂ch₂school₃, ch₂with₂h, CH₂C(O)NH₂, ch₂ch₂cooh, CH₂CH₂C(O)NH₂, CH₂CH₂CH₂CH₂NH₂, -CH₂CH₂CH₂NH (NH) NH₂, CH₂-imidazol-4-yl,

CH₂OH, CH(OH)CH₃, CH₂( (4'-OH)-Ph) , CH₂SH, or lower cycloalkyl; or (viii) R^3rd 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 and R^3b is H, where R³' is independently hydrogen or alkyl, which includes, but is not limited to, Cx-2o alkyl, Οχ-₁₀ alkyl, or Οχ-e alkyl, R³ is -OR' or -N(R³’)₂);

(d) R⁴ is hydrogen, Cx-₁₀ rent, Ci-₁₀ alkyl optionally substituted with a lower alkyl, alkoxy, di(lower alkyl)-amino, or halogen, Cx-₁₀ haloalkyl, C₃-xo cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aminoacyl, aryl, such as phenyl, heteroaryl, such as pyridinyl, substituted aryl, or substituted heteroaryl;

(e) R⁵ is H, a lower alkyl, CN, vinyl, 0(lower alkyl), hydroxyl lower alkyl, i.e., (CH2)POH, where p is 1-6, including hydroxyl methyl (CH2OH), CH2F, N3, CH2CN, CH2NH2, CH2NHCH3z CH2N(CH3)2, alkyne (optionally substituted), or halogen, including F, Cl, Br, or I, with a condition that when X is OH, base is cytosine and R⁶ is H, R⁵ it cannot be N3 and when X is OH, R⁶is CH₃ or CH₂F and B is a purine base, R⁵ cannot be H;

(f) R⁶ is H, CH₃, CH₂F, CHF₂, CF₃, F, OR CN;

12/967 (g) X is H, OH, F, OMe, halogen, NH₂, or N₃;

(h) Y is OH, Η, Ci-* alkyl, C₂-₄ alkenyl, C₂.₄alkynyl, vinyl, N₃, CN, Cl, Br, F, I, NO₂, OC(O)O(Ci-₄alkyl), OC(O)O(Ci-₄ alkyl), OC(O)O(C₂_₄ alkynyl), OC(O)O(C₂_₄ alkenyl), OCi-io haloalkyl, O(aminoacyl), 0(Ci-io acyl) , O(Ci-₄ alkyl), O(C₂.₄ alkenyl), S(Ci-₄acyl) , S(Ci-₄ rent), S(C₂.₄ alkynyl), S(C₂_₄ alkenyl), SO(Ci-₄ acyl), S0(Ci-₄ alkyl), SO(C₂_₄ alkynyl), SO(C₂.₄alkenyl), 3Ο₂(Oh-)₄ acyl), SO₂(Ci-₄ rent), SO₂(C₂_₄alkynyl), SO₂(C₂_₄ alkenyl), OS(O)₂(Ci-₄ acyl), OS(O)₂(Ci-₄ rent), OS(O)₂(C₂.₄ alkenyl), NH₂, NH(Ci-₄alkyl), NH(C₂.₄ alkenyl), NH(C₂.₄ alkynyl), NH(Ci-₄acyl), N(Ci-₄ rent)₂, N(Ci-i₈ acyl)₂, in which alkyl, alkynyl, alkenyl and vinyl are optionally substituted by N₃, CN, one to three halogens (Cl, Br, F, I) , NO₂, C(O)O(C!-₄ alkyl) , C(O)O(Ci-₄ alkyl), C(O)O(C₂.₄alkynyl), C(O)O(C₂-₄ alkenyl), O(Ci-₄ acyl), O(Ci-₄alkyl), O(C₂.₄ alkenyl), S(Ci-₄ acyl), S(Ci-₄ rent), S(C₂-₄ alkynyl), S(C₂.₄ alkenyl), SO(Ci_₄ acyl), SO(Ci-₄alkyl), SO(C₂.₄ alkynyl), SO(C₂.₄ alkenyl), SO₂(C!-₄acyl), SO₂(Ci-₄ rent), SO₂(C₂_₄ alkynyl), SO₂(C₂-₄alkenyl), OS(O)₂(Ci-₄ acyl), OS(O)₂(Ci-₄ rent), OS(O)₂(C₂-₄ alkenyl), NH₂, NH(Ci-₄ alkyl), NH(C₂.₄alkenyl), NH(C₂.₄ alkynyl), NH(Ci-₄ acyl), N(C!-₄alkyl) 2, N(Ci-₄ acyl)₂;

the base is a modified or naturally occurring pyrimidine or purine base represented by the following structures:

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<img file="BRPI0809654A2_D0002.tif" />

where

Z is N or CR¹²;

R⁷, R⁸, R⁹, R¹⁰, and R^i;Lare independently H, F, Cl, 10 Br, I, OH, OR', SH, SR', NH2, NHR¹ , NR'2, Ci-Cg lower alkyl, Cj.Cg halogenated lower alkyl (F, Cl, Br, I), Cj.Cg lower alkenyl₂-C₆, lower alkenyl (F, Cl, Br, I) halogenated from C₂-C₆, C lower alkynyl₂-C₆ such as C^CH, 15 C halogenated lower alkynyl (F, Cl, Br, I).₂-C₆, Ci-C lower alkoxy₆, lower alkyl (F, Cl, Br,

I) Ci-C halogenation₆, CO₂H, CO₂R', CONH₂, CONHR', CONR'₂, CH=CHCO₂H, or CH=CHCO₂R', wherein R' is an optionally substituted alkyl, which includes, but is not limited to, a Ci-₂₀ optionally substituted alkyl, an optionally substituted C 1-6 alkyl, an optionally substituted lower alkyl; an optionally substituted cycloalkyl; an optionally substituted alkynyl of C₂-C₆, an optionally substituted lower alkenyl of C₂-C₆, or optionally substituted acyl, which includes but is not limited to C(O) alkyl, C(O)(Ci-₂₀ alkyl), C(O)(Ci-₁₀alkyl), or C(0)(lower alkyl) or alternatively, in place of NR'₂, each R' comprises at least one C atom which is joined to form a heterocycle comprising at least two carbon atoms; e

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R¹² is a H, halogen (including F, Cl, Br, I) , OH, OR', SH, SR', NH2, NHR', NR'2z lower alkyl NO2 of Ci-C6, lower alkyl (F, Cl, Br, I) halogenated of Ci-C6, lower alkenyl of C2-C6, lower alkenyl (F, Cl, Br, I) halogenated of C2-C6 , lower alkynyl of C2-C6, C2-C6 halogenated lower alkynyl (F, Cl, Br, I), Ci-C6 lower alkyl, Ci-C6 halogenated lower alkyl (F, Cl, Br, I), CO2H, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R' ; with the condition that when the base is represented by the structure c with R¹¹ being hydrogen, R¹² is not: (i) -C^CH, (ii) -C=CH2, or (iii) -N0₂.

DEFINITIONS

The term an entity used herein refers to one or more of the entities; for example, a compound refers to one or more compounds or at least one compound. Thus, the terms one, one or more, and at least one may be used interchangeably herein.

The phrase as defined above refers to the first definition provided in the Summary of the Invention.

The terms optional or optionally as used herein mean that an event or circumstance described below may, but not necessarily, occur and that the description includes both instances in which the event or circumstance occurs and instances in which it does not occur. For example, optional binding means that the binding may or may not be present and that the description includes single, double, or triple binding.

The term independently is used here to indicate that a variable is applied in any case regardless of the presence or absence of a variable with

15/967 same or different definition within the same compound. Thus, in a compound in which R appears twice and is defined as independent of carbon and nitrogen, both Rs can be carbon, both Rs can be 5 nitrogen, or one R' can be carbon and the other nitrogen.

The term alkenyl refers to an unsubstituted hydrocarbon chain with 2 to 10 carbon atoms having one or two olefinic double bonds, preferably an olefinic double bond. The term C₂-_N alkenyl refers to an alkenyl that comprises from 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-io alkenyl refers to an alkenyl comprising from 15 2 to 10 carbon atoms. The term C₂-₄ alkenyl refers to an alkenyl that comprises from 2 to 4 carbon atoms. Some examples include, but are not limited to, vinyl, 1-propenyl, 2-propenyl (allyl) or 2-butenyl (crotyl).

The term halogenated alkenyl refers to an alkenyl that comprises at least one F, Cl, Br, and I.

The term alkyl refers to a branched or unbranched, saturated, monovalent hydrocarbon residue chain containing from 1 to 30 carbon atoms. The term Ci-μ alkyl refers to an alkyl that comprises from 1 to 25 M carbon atoms, where M is an integer with the following values: 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, 29 or 30. The term Ci-₄ alkyl refers to an alkyl containing 1 to 4 carbon atoms. The term lower alkyl 30 denotes chain hydrocarbon residue

16/967 branched or linear containing from 1 to 6 carbon atoms. Ci-20 alkyl as referred to here is an alkyl that comprises from 1 to 20 carbon atoms. Ci~i₀ alkyl as referred to here is an alkyl that comprises from 1 to 10 carbons. Some examples of the alkyl group include, but are not limited to, lower alkyl groups including methyl, ethyl, propyl, i-propyl, n-butyl, i-butyl, t-butyl or pentyl, isopentyl, neopentyl, hexyl, heptyl and octyl. The term (ar)alkyl or (heteroaryl)alkyl indicates the alkyl group which may optionally be replaced by an aryl or heteroaryl group, respectively.

The term cycloalkyl refers to a substituted or unsubstituted carbocycle, where the carbocycle contains from 3 to 10 carbon atoms; preferably 3 to 8 carbon atoms; but preferably from 3 to 6 carbon atoms (ie lower cycloalkyl). Some examples of cycloalkyl groups include, but are not limited to, cyclopropyl, 2-methylcyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

The term cycloalkyl alkyl refers to an additional substituted or unsubstituted alkyl substituted by a lower cycloalkyl. Some examples of cycloalkyl alkyl include, but are not limited to, any of methyl, ethyl, propyl, i-propyl, n-butyl, i-butyl, t-butyl or pentyl, isopentyl, neopentyl, hexyl, heptyl and octyl which may be substituted by cyclopropyl, 2-methylcyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.

The term cycloheteroalkyl refers to a substituted or unsubstituted heterocycle, in which the heterocycle contains from 2 to 9 carbon atoms; preferably 2 to 7 carbon atoms; more

17/967 preferably from 2 to 5 carbon atoms. Some examples of cycloheteroalkyls include, but are not limited to, aziridin-2-yl, NC₁_₃-alkyl-aziridin-2-yl, azetidinyl, N-Ci-3-alkyl-azetidin-m'-yl, pyrrolidin-m'-yl, N-C1-3alkyl-pyrrolidin-m¹-yl, piperidin-m'-yl and N-Cx-alkylpiperidin-m'-yl, where m' is 2, 3, or 4 depending on the cycloheteroalkyl. Specific examples of N-C1-3alkyl-cycloheteroalkyls include, but are not limited to, N-methylaziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-2-yl, N-methyl-piperidin-3-yl, and N-methyl-piperidin-4-yl. Regarding the example of R⁴, the point of attachment between the carbon of the cycloheteroalkyl ring and the oxygen occurs at any one of m'

The term heterocycle refers to a substituted or unsubstituted heterocycle containing carbon, hydrogen and at least one of N, 0 and S, where C and N can be trivalent or tetravalent, that is, sp²- or sp³hybridized Some examples of heterocycles include, but are not limited to, aziridine, azetidine, pyrrolidine, piperidine, imidazole, oxazole, piperazine, etc. In relation to piperazine, as related to R¹⁰ for NR'₂, the corresponding opposite nitrogen atom of piperazinyl is replaced by a lower alkyl represented by the following structure: / lower alkyl

Preferably, the opposite nitrogen of piperazinyl is substituted by a methyl group.

The term halogenated alkyl (or haloalkyl) se

18/967 refers to a branched or unbranched chain alkyl comprising at least one F, Cl, Br and 1.0 term Ci-_Mhaloalkyl refers to an alkyl comprising from 1 to M carbon atoms comprising at least one F, Cl, Br and I, where M is an integer with the following values: 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, 29, or 30. The term Ci-3 haloalkyl refers to a haloalkyl containing 1 to 3 carbon atoms and at least one F, Cl, Br, and I. The term halogenated lower alkyl (or lower haloalkyl) refers to a haloalkyl containing 1 to 6 carbon atoms and at least one F, Cl, Br, and I. Some examples include, but are not limited to, fluoromethyl, chloromethyl, bromomethyl, iodomethyl, difluoromethyl, dichloromethyl, dibromomethyl, diiodomethyl, trifluoromethyl, trichloromethyl, tribromomethyl, triiodomethyl, 1fluoroethyl, 1-chloroethyl, 1-bromoethyl, 1-iodoethyl, 2fluoroethyl, 2-chloroethyl, 2-bromoethyl, 2-iodoethyl, 2-2difluoroethyl, 2-2-dichloroethyl, 2-2-dibromomethyl, 2-2diiodomethyl, 3-fluoropropyl, 3-chloropropyl, 3bromopropyl, 2-2-2-trifluoroethyl or 1-1-2-2-2pentafluoroethyl.

The term alkynyl refers to a radical with a branched or unbranched hydrocarbon chain with 2 to 10 carbon atoms, preferably with 2 to 5 carbon atoms and with a triple bond. The term C2-M alkynyl refers to an alkenyl that comprises from 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 CC₂-₄alkynyl refers to an alkynyl comprising from 2 to 4

19/967 ' carbon atoms. The term C₂~io alkynyl refers to an alkynyl that comprises from 2 to 10 carbon atoms. Examples include, but are not limited to, ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl or 3-butynyl.

The term halogenated alkynyl refers to a radical with a branched or unbranched hydrocarbon chain with 2 to 10 carbon atoms, preferably with 2 to 5 carbon atoms and with a triple bond and at least one F, Cl, Br and I.

The term cycloalkyl refers to a saturated carbocyclic ring comprising 3 to 8 carbon atoms, ie cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl. 0 term C₃-₇cycloalkyl as used herein refers to a cycloalkyl 15 containing from 3 to 7 carbons in the carbocyclic ring.

The term alkoxy refers to an -O-alkyl group or an -O-cycloalkyl group, where alkyl and cycloalkyl are as defined above. Some examples of -Oalkyl groups include, but are not limited to, methoxy, ethoxy, n-propyloxy, i-propyloxy, n-butyloxy, i-butyloxy, t-butyloxy. The term Lower Alkoxy as used herein denotes an Alkoxy group with a Lower Alkyl group as previously defined. The term Ci-i₀ Alkoxy refers to an -O-alkyl where alkyl is Ci-i₀. Some examples of -O25 cycloalkyl groups include, but are not limited to, -Oc-propyl, -O-cbutyl, -Oc-pentyl, and -O-c-hexyl.

The term halogenated alkoxy refers to an -Oalkyl group in which the alkyl group comprises at least one F, Cl, Br and I.

The term halogenated lower alkyl refers to um

20/967 group -O-(lower alkyl) in which the lower alkyl group comprises at least one F, Cl, Br and I.

The term amino acids naturally includes α, β γ or δ synthetic amino acids and includes, but is not limited to, amino acids found in proteins, namely glycine, alanine, valine, leucine, isoleucine, methionine, phenylalanine, tryptophan, proline, serine, threonine, cysteine, tyrosine, asparagine, glutamine, aspartate, glutamate, lysine, arginine and histidine. In a preferred embodiment, the amino acid is in an L configuration. Alternatively, the amino acid may be a derivative of alanyl, valinyl, leucinyl, isoleucinyl, prolinyl, phenylalaninyl, tryptophanyl, methioninyl, glycinyl, serinyl, threoninyl, cysteinyl, tyrosinyl, asparaginyl, glutaminyl, aspartoyl, glutaroyl, lysinyl, argininyl, histidinyl, β-alanyl, β-valinyl, β-leukinyl, βisoleucinyl, β-prolinyl, β-phenylalaninyl, β-tryptophanyl, β-methioninyl, β-glycinyl, β-serinyl, βthreoninyl, β-cysteinyl, β-tyrosinyl, β-asparaginyl, β-glutaminyl, β-aspartoyl, β-glutaroyl, β-lysinyl, β-argininyl or β-histidinyl. When the term amino acid is used, it is considered a specific and independent disclosure of each of the esters α, β γ or δ glycine, alanine, valine, leucine, isoleucine, methionine, phenylalanine, tryptophan, proline, serine, glutamine threonine, cysteine, tyrosine, asparagine, aspartate, glutamate, lysine, arginine and histidine in D and L configurations.

The term aminoacyl includes N-Nin-substituted, NN-monosubstituted and NN-disubstituted derivatives of

21/967 naturally occurring ea, β γ or δ synthetic aminoacyls, where aminoacyls are derived from amino acids. The amino nitrogen can be substituted or unsubstituted. When the amino-nitrogen is substituted, the nitrogen is mono- or di-substituted, where the substituent attached to the amino-nitrogen is a lower alkyl or an alkaryl. An example of its use for Y, the expression O(aminoacyl) is used. It is understood that the C3' carbon of ribose is linked to oxygen O, which is then linked to the carbonyl carbon of aminoacyl.

The terms alkyl or arylamine refers to an amine group that has one or more alkyl or aryl substituents, respectively.

The term protected, as used herein and unless otherwise defined, refers to a group that is added to an oxygen, nitrogen or phosphorus atom to prevent its 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. Some non-limiting examples include: C(O)-alkyl, C(O)Ph, C(O)aryl, CH₃, CH₂-rent, CH₂alkenyl, CH₂Ph, CH₂-arila, CH₂O-alkyl, CH₂O-arila, SO₂rent, S0₂-aryl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl and 1-3-(1-1-3-3tetraisopropyldisiloxanilidene).

The term aryl, as used herein, and unless otherwise defined, refers to a substituted or unsubstituted phenyl (Ph), biphenyl, or naphthyl, preferably the term aryl refers to substituted or unsubstituted phenyl. The aryl group can be replaced by an or

22/967 plus moieties selected from hydroxyl, F, Cl, Br, I, amine, alkyl, arylamine, alkoxy, aryloxy, nitro, cyano, sulfonic acid, sulfate, phosphonic acid, phosphate and phosphonate, whether unprotected, or protected, if necessary, as known to those skilled in the art, for example, as described in TW. Greene and PGM Wuts, Protective Groups in Organic Synthesis, 3rd ed. , John Wiley &amp; Sons, 1999.

The terms alkaryl or alkylaryl refer to an alkyl group with an aryl substituent, such as benzyl. The terms aralkyl or arylalkyl refer to an aryl group with an alkyl substituent.

The term di(lower alkyl)amino-lower alkyl refers to a lower alkyl substituted by an amine group that is substituted by two lower alkyl groups. Some examples include, among others, (CH₃)₂NCH₂, (CH₃)₂NCH₂CH₂, (CH₃)₂NCH₂CH₂CH_2z etc. The above examples show a lower alkyl substituted at the end of the carbon atom with an NN-dimethyl-amine substituent. These are merely examples and are not intended to limit the meaning of the expression di (lower alkyl)aminolower alkyl so as to require the same. It is contemplated that the lower alkyl chain may be replaced by an NN-di(lower alkyl)-amine at any point along the chain, for example, CH₃CH (N-(lower alkyl)₂) /-ítt L,M2\~«rl2 ·

The term halo, as used herein, includes chlorine, bromine, iodine and fluorine.

The term acyl refers to a substituent containing a carbonyl moiety and a non-carbonyl moiety. The fraction

23/967 carbonyl contains a double bond between the carbonyl carbon and a heteroatom, where the heteroatom is chosen from O, N and S. When the heteroatom is N, the N will be replaced by a lower alkyl. The non-carbonyl moiety is selected from a linear branched cyclic alkyl which includes, but is not limited to, a linear C 1-20 branched alkyl, C 1-10 alkyl or lower alkyl; alkoxyalkyl, including methoxymethyl; aralkyl, including benzyl; aryloxyalkyl, such as phenoxymethyl; or aryl, including phenyl optionally substituted by halogen (F, Cl, Br, I), hydroxyl, C_x to C₄-alkyl or Ci to C₄ alkoxy, sulfonate esters, such as alkyl or sulfonyl aralkyl, including methanesulfonyl, mono, di, or triphosphate, trityl or monomethoxytrityl, substituted benzyl, trialkylsilyl (eg, dimethyl-t-butylsilyl) or diphenylmethylsilyl esters. When at least one aryl group is in a non-carbonyl moiety, it is preferred that the aryl group comprises a phenyl group.

The term lower acyl refers to an acyl group in which the non-carbonyl moiety is a lower alkyl.

The term purine base or pyrimidine includes, among others, adenine, N⁶-alkylpurines, N⁶-acylpurines (where acyl is C(O)(alkyl, aryl, alkylaryl or arylalkyl), N^yes-benzylpurine, N⁶-halopurine, N^yes-vinylpurine, N⁶-acetylenic purine, N^yes-acyl purine, N^yes-hydroxyalkyl purine, N^yesalkylaminopurine, N^yes-thioalkyl purine, N²-alkylpurines, N²alkyl-6-thiopurines, thiamine, cytosine, 5-fluorocytosine, 5-methylcytosine, 6-azapyrimidine, including 6-azacytosine, 2and/or 4-mercaptopyrimidine, uracil, 5-halouracil, including 5-fluorouracil, C⁵-alkylpyrimidines, C⁵-benzylpyrimidines,

24/967

C⁵-halopyrimidines, C⁵-vinylpyrimidine, C⁵-acetylenic pyrimidine, C⁵-acyl pyrimidine, C⁵-hydroxyalkyl purine, C⁵-amidopyrimidine, C⁵-cyanopyrimidine, , C⁵-iodopyrimidine, C^yes-modo-pyrimidine, C⁵-Br-vinyl pyrimidine, C⁶-Br-vinyl pyrimidine , C⁵-nitropyrimidine, C⁵-amino-pyrimidine, N²alkylpurines, N²-alkyl-6-thiopurines, 5-azacytidinyl, 5azauracilyl, triazolopyridinyl, imidazolopyridinyl, pyrrolopyrimidinyl and pyrazolopyrimidinyl. Purine bases include, among others, guanine, adenine, hypoxanthine, 2-6-diaminopurine and 6-chloropurine. The nitrogen and oxygen functional groups on the base can be protected as desired. Suitable protecting groups are well known to those skilled in the art, and include trimethylsilyl, dimethylhexylsilyl, t-butyldimethylsilyl and t-butyldiphenylsilyl, trityl, alkyl, acyl groups such as acetyl and propionyl, methanesulfonyl and p-toluenesulfonyl. The term tautomerism and tautomers have their meanings clearly accepted. 0 term P * means that the phosphorus atom is chiral and has a corresponding Cahn-IngoldPrelog designation of R or S, which have their meanings fully accepted. It is mentioned that the compounds of formula I are racemic because of the chirality at phosphorus. Depositors contemplate the use of racemate and/or resolved enantiomer. In some cases, an asterisk does not appear near the phosphoramidate phosphorus atom. In these cases, it is understood that the phosphorus atom is chiral and those skilled in the art will understand that this must be used, unless the substituents attached to the phosphorus exclude the

25/967 possibility of chirality in phosphorus, such as in P (O) Cl₃.

DETAILED DESCRIPTION OF THE INVENTION

One aspect of the present invention relates to a compound, its salts, hydrates, solvates, crystalline forms and the like represented by formula I:

<img file="BRPI0809654A2_D0003.tif" />

where (a) RI is hydrogen, n-alkyl; branched alkyl; cycloalkyl; or aryl, which includes, but is not limited to, phenyl or naphthyl, wherein phenyl or naphthyl is optionally substituted with at least one of Ci-₆ rent, C₂.₆alkenyl, C₂_₆ alkynyl, Ci-₆ alkoxy, F, Cl, Br, I, nitro, cyano, Ci-6 haloalkyl, -N(R^X')2, Ci-6 acylamino, -NHSO2C1.6 alkyl, -SO2N(R^X')2, COLOR¹”, and -SO2Ci-6 alkyl; (RI' is independently hydrogen or alkyl, which includes, but is not limited to, Cx-20 alkyl, Cx-10 alkyl, or Ci-6 alkyl, Rl is -OR' or -N(R¹’)2);

(b) R2 is hydrogen, C i-₁₀ rent, R^3rd or R3b and R2 together are (CH₂)n so as to form a cyclic ring that includes the adjacent atoms N and C, C (0) CR^3rdR^3bNHR^x, where n is 2 to 4 and R¹, R^3rd, and R^3b;

(c) R^3rd and R^3b are (i) independently selected from hydrogen, Ci-ho alkyl, cycloalkyl, - (CH2) c (NR³') 2, Ci-6 hydroxyalkyl, -CH₂SH, - (CH₂) ₂S(O)dMe, (CH₂) ₃NHC(=NH)NH₂, (1H-indol-3-yl)methyl, (1H-imidazol-4-

26/967 iDmethyl, - (CH2) eCOR³, aryl and aryl Cl-3 alkyl, said aryl groups optionally substituted by a group selected from hydroxyl, Ci-10 alkyl, Cl-6 alkoxy, halogen, nitro and cyano; (ii) R^3rd and R^3b both are Cl-6 alkyl; (iii) R^3rd and R^3b together they are (CH2)_f so as to form a spiral ring; (iv) R^3rd is hydrogen and R^3b and R² together they are (CH2)n so as to form a cyclic ring that includes the adjacent atoms N and C (v) R^3b is hydrogen and R^3rd and R²together are (CH2)n so as to form a cyclic ring that includes the adjacent atoms N and C, where c is 1 to 6, déOa 2, eé0a3, f is 2 to 5, né2a4, and where R³' is independently hydrogen or Ci-S alkyl and R³ is -OR' or —N(R³)2); (vi) R^3rd 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 lower cycloalkyl; or (viii) R^3rd 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 and R^3b is H, where R³' is independently hydrogen or alkyl, which includes, but is not limited to, Ci-20 alkyl, Ci-10 alkyl, or Ci-6 alkyl, R³” is -OR' or -N(R³')2);

(d) R⁴ is hydrogen, Ci-i₀ alkyl, Ci_ i θ C3 1. 3. 1 optionally substituted with a lower alkyl, alkoxy, di(lower alkyl)-amino, or halogen, Ci-₁₀ haloalkyl, C₃-io cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aminoacyl, aryl, such as phenyl, heteroaryl, such

27/967 as, pyridinyl, substituted aryl, or substituted heteroaryl;

(e) R⁵ is H, a lower alkyl, CN, vinyl, 0(lower alkyl), hydroxyl lower alkyl, that is, (CH2)POH, where pel -6, including hydroxyl methyl (CH2OH), CH2F, N3, CH2CN, CH2NH2, CH2NHCH3, CH2N(CH3)2, alkyne (optionally substituted), or halogen, including F, Cl, Br, or I, with the proviso that when X is OH, base is cytosine and R⁶ is H, R⁵ it cannot be N3 and when X is OH, R6 is CH₃ or CH₂F and B is a purine base, R⁵ it cannot be Η;

(f) R^yes 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, Ci-4 alkyl, C₂.₄ alkenyl, C₂.₄alkynyl, vinyl, N₃, CN, Cl, Br, F, I, NO₂, OC(O)O(Ci-₄alkyl), OC(O)O(Ci-₄ alkyl), OC(O)O(C₂_₄ alkynyl), OC(O)O(C₂-₄ alkenyl), OCi-i₀ haloalkyl, O (aminoacyl), 0(Ci-io acyl), 0(Ci-₄ rent), 0(C₂-₄ alkenyl), S(Ci-₄acyl), S(Ci-₄ rent), S(C₂-₄ alkynyl), S(C₂_₄ alkenyl), SO(Ci-4 acyl), SO(Ci-₄ alkyl), SO(C₂.₄ alkynyl), SO(C₂.₄alkenyl), SO₂(C_x-₄ acyl), SO₂(Ci-₄ rent), SO₂(C₂-₄alkynyl), SO₂(C₂-₄ alkenyl), OS(O)₂(Ci-₄ acyl), OS(O)₂(Ci-₄ rent), OS(O)₂(C₂.₄ alkenyl), NH₂, NH(Ci-₄alkyl), NH(C₂-₄ alkenyl), NH(C₂-₄ alkynyl), NH(Ci-₄acyl), N(Ci-₄ rent)₂, N(C1-18 acyl)₂, in which alkyl, alkynyl, alkenyl and vinyl are optionally substituted by N₃, CN, one to three halogens (Cl, Br, F, I), N0₂, C(O)O(Ci-4 alkyl), C(O)O(Ci-₄ alkyl), C(O)O(C₂.₄alkynyl), C(O)O(C₂.₄ alkenyl), O(Ci-₄ acyl), 0(C_x-₄alkyl), O(C₂_₄ alkenyl), S(C₃-₄ acyl), S(Ci-₄ rent), !₂-4 alkynyl), S(C₂-₄ alkenyl), SO (Ci-4 acyl), SO(Ci-₄

28/967 rent), SO(C₂-4 alkynyl) , SO(C₂_₄ alkenyl), SO₂(Ci-₄ acyl) , SO₂(Ci-₄ rent), SO₂(C₂.₄ alkynyl), SO₂(C₂.₄alkenyl), OS(O)₂(C_X.₄ acyl), OS(O)₂(Ci-₄ alkyl), OS(0)2(C₂_₄ alkenyl), NH₂, NH(C_X.₄ alkyl), NH(C₂.₄alkenyl), NH(C₂.₄ alkynyl), NH(Ci-₄ acyl), N(C_X_₄rent)₂, N(C_x-₄ acyl)₂;

the base is a modified or naturally occurring pyrimidine or purine base represented by the following structures:

<img file="BRPI0809654A2_D0004.tif" />

abc d where Z is N or CR¹²;

R⁷, R⁸, R⁹, R¹⁰, and R^1:Lare independently H, F, Cl, Br, I, OH, OR', SH, SR', NH2, NHR¹ , NR' 2, Ci-C lower alkyl₆, lower alkyl (F, Cl, Br, I) halogenated from C_xC_yes, C lower alkenyl₂-C_and, lower alkenyl (F, Cl, Br, I) halogenated from C₂-C₆, C lower alkynyl₂-C6 such as C=CH, lower alkynyl (F, Cl, Br, I) halogenated from C₂-C₆, Ci-C lower alkoxy_yes, Ci-C halogenated lower alkyl (F, Cl, Br, I)._yes, C0₂H, CO₂R', CONH₂, CONHR', CONR'₂, CH=CHCO₂H, or CH=CHCO₂R', wherein R' is an optionally substituted alkyl, which includes, but is not limited to, a Ci-₂₀ optionally substituted alkyl, an optionally substituted C1-io alkyl, an optionally lower alkyl

29/967 replaced; an optionally substituted cycloalkyl; an optionally substituted alkynyl of C₂-C₆, an optionally substituted lower alkenyl of C₂-C₆, or optionally substituted acyl, which includes but is not limited to C(O) alkyl, C(O) (C^o alkyl), C(0) (Ci-io alkyl), or C(O) (lower alkyl) or alternatively, in place of NR'₂, each R' comprises at least one C atom which is joined to form a heterocycle comprising at least two carbon atoms; e

R12 is H, halogen (including F, Cl, Br, I), OH, OR', SH, SR', NH₂, NHR', NR'₂, lower alkyl N02 of C_xC₆, lower alkyl (F, Cl, Br, I) halogenated from Ci-C₆, C lower alkenyl₂-C₆, lower alkenyl (F, Cl, Br, I) halogenated from C₂-C₆ , C lower alkynyl₂-C_yes, lower alkynyl (F, Cl, Br, I) halogenated from C₂-C₆, Ci~C lower alkoxy₆, Ci-C halogenated lower alkyl (F, Cl, Br, I)._yes, CO₂H, CO₂R', CONH₂, CONHR', CONR'₂, CH=CHCO₂H, or CH=CHCO₂R'; with the condition that when the base is represented by the structure c with R¹¹ being hydrogen, R¹² is not: (i) -C=CH, (ii) -C=CH₂, or (iii) -NO₂.

As can be seen from the structure of formula I above, there are various ways of expressing the different modalities and aspects of each modality of the present invention. As can be seen below, the inventors have disclosed some embodiments directed to the compound of formula I, each having various aspects based on the identity of the modified purine or pyrimidine base. This is not intended to be an explicit or implicit admission that the three modalities are independent or distinct, nor should it be interpreted as such. In fact, it is meant to convey

30/967 the information so that the total content of the present invention can be understood. In addition, the following modalities and their aspects should not be restricted to the total content of the invention as noted by structure 5 of formula I.

The first mode of the invention is directed to the compound represented by the formula II:

<img file="BRPI0809654A2_D0005.tif" />

(a) RI is hydrogen, n-alkyl; branched alkyl;

cycloalkyl; or aryl, which includes, but is not limited to, phenyl or naphthyl, wherein phenyl or naphthyl is optionally substituted with at least one of Ci-₆ rent, C₂_₆alkenyl, C₂__yes alkynyl, C_x-₆ alkoxy, F, Cl, Br, I, nitro, cyano, Ci-6 haloalkyl, -N(R¹’)₂, C_x.₆ acylamino, -NHSO₂Ci-₆ rent, -SO^R¹')^ COLOR¹, and -SO2CX-6 alkyl; (RI' is independently hydrogen or alkyl, which includes, but is not limited to, Cx-20 alkyl, Cx.Xo alkyl, or Cx-e alkyl, Rl is -OR' or -N(R¹')2);

(b) R2 is hydrogen, C_X-_Xo rent, R^3rd or R3b and R2 together are (CH₂)n so as to form a cyclic ring that

31/967 includes adjacent N and C atoms_z C (O) CR^3rdR^3bNHR¹, where n is 2 to 4 and R¹, R^3rd, and R^3b;

(c) R^3rd and R^3b are (i) independently selected from hydrogen, Ci-ho alkyl, cycloalkyl, - (CH2) c (NR³') 2, 5 Ci-6 hydroxyalkyl, -CH₂SH, - (CH₂) ₂S(O)dMe,(CH2)₃NHC(=NH)NH₂, (1H-indol-3-yl)methyl, (1H-imidazol-4yl)methyl, - (CH₂)eCOR³', aryl and aryl Cl-3 alkyl, said aryl groups optionally substituted by a group selected from hydroxyl, C1-10 alkyl, Cl-6 alkyl, 10 halogen, nitro and cyano; (ii) R^3rd and R^3b both are C 1-6 alkyl; (iii) R^3rd and R^3b together they are (CH2)_f so as to form a spiral ring; (iv) R^3rd is hydrogen and R^3b and R² together they are (CH₂)n so as to form a cyclic ring that includes the adjacent atoms N and C (v) R^3b is hydrogen and R^3rd and R² together they are (CH₂)n so as to form a cyclic ring that includes adjacent atoms N and C, where c is 1 to 6, déOa 2, eé0a3, f is 2 to 5, né2a4, and where R³' is independently hydrogen or Ci-6 alkyl and R³ is -OR' or —N(R³)2); (vi) R^3rd is H and R^3b is H, CH₃, CH₂CH₃, CH(CH₃)₂, 20 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; or (viii) R^3rd is CH3, -CH2CH3, CH(CH3)2, CH2CH(CH3)2, 25 CH(CH3)CH2CH3, CH2Ph, CH2-indol-3 - ila, -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 and R^3b is H, where R³' is independently hydrogen or alkyl, which includes, but is not limited to, Ci-20 alkyl, Οχ.χο alkyl,

32/967 or Ci-6 alkyl, R³ is -OR' or -N(R³')₂);

(d) R4 is hydrogen, Ci-χ is alkyl, Ci-i₀ alkyl optionally substituted with a lower alkyl, alkoxy, di(lower alkyl)-amino, or halogen, Ci-i₀ haloalkyl, C₃-io cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aminoacyl, di(lower alkyl), aryl, such as phenyl, heteroaryl, such as pyridinyl, substituted aryl, or substituted heteroaryl;

(e) R⁵ is H, a lower alkyl, CN, vinyl, O(lower alkyl), hydroxyl lower alkyl, that is, (CH2)POH, where p is 1-6, including hydroxyl methyl (CH2OH), CH2F, N3, CH2CN, CH2NH2, CH2NHCH3, CH2N(CH3)2, alkyne (optionally substituted), or halogen, including F, Cl, Br, or I, provided that when X is OH, base is cytosine and R⁶ is H, R⁵ it cannot be N3 and when X is OH, R⁶is CH₃ or CH₂F and 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, Cx-4 alkyl, C₂_₄ alkenyl, C₂,₄alkynyl, vinyl, N₃, CN, Cl, Br, F, I, NO₂, 0C(0)0(Ci-₄alkyl), OC(O)O(Ci-₄ alkyl), OC(O)O(C₂.₄ alkynyl), OC(O)O(C₂_₄ alkenyl), OC1-10 haloalkyl, O (aminoacyl) , 0(Ci-io acyl) , O(Ci-₄ alkyl), O(C₂.₄ alkenyl), S(C_X.₄acyl) , S(Ci-₄ rent), S(C₂-₄ alkynyl), S (C₂-₄ alkenyl), SO(Ci-₄ acyl), SO(Ci-₄ alkyl), SO(C₂-₄ alkynyl) , SO(C₂.₄alkenyl), SO₂(Ci-₄ acyl), SO₂(Ci-₄ rent), S0₂ (C₂-₄alkynyl), SO₂(C₂-₄ alkenyl), OS(O)₂(Cx-₄ acyl), OS(O)₂(Ci-₄ rent), OS(O)₂(C₂_₄ alkenyl), NH₂, NH(Ci-₄alkyl), NH(C₂-₄ alkenyl), NH(C₂.₄ alkynyl), NH(Ci-₄acyl), N(Ci-₄ rent)₂, N(C1-18 acyl)₂, in which it is rented,

33/967 alkynyl, alkenyl and vinyl are optionally substituted by N₃, CN, one to three halogens (Cl, Br, F, I), N0₂, C(O)O(Ci-₄ alkyl), C(0)0(Ci-₄ alkyl), C(O)O(C₂.₄alkynyl), C(O)O(C₂_₄ alkenyl), O(C₁_₄ acyl) , 0(C_x-₄ alkyl), O(C₂.₄ alkenyl), S(Ci-₄ acyl), S(Ci-₄ rent), S(C₂.₄ alkynyl), S(C₂-₄ alkenyl), SO(C_x-₄ acyl), SO(C!.₄alkyl), SO(C₂.₄ alkynyl), SO(C₂.₄ alkenyl), SO₂(Ci_₄acyl), SO₂(Ci-₄ rent), SO₂(C₂_₄ alkynyl), SO₂(C₂-₄alkenyl), OS(O)₂(C_x-₄ acyl), OS(O)₂(Ci-₄ rent), 10 OS(O)₂(C₂_₄ alkenyl), NH₂, NH(C_x-₄ alkyl), NH(C₂.₄ alkenyl), NH(C₂.₄ alkynyl), NH(Ci-₄ acyl), N(Ci-₄rent)₂, N(C_X.₄ acyl)₂;

(i) R⁷, R⁸, R³ are independently H, F, Cl, Br, I, OH,

OR', SH, SR', NH₂, NHR', NR'₂, lower alkyl, halogenated lower alkyl 15 (F, Cl, Br, I), C lower alkenyl₂-C₆, CO₂H, CO₂R'_z CONH₂, CONHR', CONR'₂, where R' is a Ci-₂₀rent; a C_x.₂the cycloalkyl; a C₂-C_yes alkenyl, a C₂-C₆alkynyl.

The first aspect of the first modality is directed to the compound represented by formula 1-1: where (a) R¹ is hydrogen, n-alkyl, or aryl, which includes, but is not limited to, phenyl or naphthyl, wherein phenyl or naphthyl is optionally substituted with at least one 25 Ci-6 alkyl, Ci-₆ alkoxy, F, Cl, Br, I, nitro, cyano, Ci-₆haloalkyl;

(b) R² is hydrogen or CH₃ ;

(c) R^3rd and R^3b are independently (i) R^3rd is hydrogen and R^3b and R² together they are (CH₂)_n so that they form 30 a cyclic ring that includes the N and C atoms together (v) R^3b is

34/967 hydrogen and R^3rd and R² together they are (CH2)n so that they form a cyclic ring that includes N and C atoms together, where c is 1 to 6, dé0a2, eé0a3, f is 3 to 5, né2a4, and where R³' is independently hydrogen or Ci-6 alkyl and R³ is -OR' or -N(R³')2); (vi) R^3rd is H and R^3b 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 (viii) R^3rd is CH₃, CH(CH₃)₂, CH₂CH(CH₃)₂, CH(CH₃) CH₂CH₃, CH₂Ph, CH₂indol-3-yl, -CH₂CH₂SCH₃, CH₂CO₂H, CH₂C(O)NH₂, CH₂CH₂COOH, CH₂CH₂C(O)NH₂, CH₂CH₂CH₂CH₂NH₂, -CH₂CH₂CH₂NHC(NH)NH₂, CH₂imidazol-4-yl, CH₂OH, CH(OH)CH₃, CH₂ ( (4'-OH)-Ph) , or CH₂SH and R^3b is H;

(d) R4 is hydrogen, Οχ-₁₀ alkyl, Ci-ho alkyl optionally substituted with a lower alkyl, alkoxy, di(lower alkyl)-amino, or halogen, Ci-ho haloalkyl, C₃-io cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aminoacyl, aryl, such as phenyl, heteroaryl, such as pyridinyl, substituted aryl, or substituted heteroaryl;

(e) R⁵ is H, CN, CH3, vinyl, OCH3, OCH2CH3, CH2OH, CH2 (halo), such as CH2F, N3, CH2CN, CH2N3, CH2NH2, CH2NHCH3, CH2N(CH3)2, halogen, including F, Cl, Br, or I, with the proviso that when X is OH, the base is a cytosine and R⁶ is H, 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, Cx-4 alkenyl, vinyl, N₃, CN, Cl, Br, F, I, O(Ci-₆ acyl) , O(Ci-₄ rent), NH₂, ΝΗ(Οχ-₄ rent),

35/967

NH(C₂-4 alkenyl) , NH(C₂.₄ alkynyl), NH(Ci-₄ acyl) , N(Ci-₄rent)₂, N(Ci-i₈ acyl)₂, where alkyl, alkynyl, alkenyl and vinyl are optionally substituted by N₃, CN, one to three halogens (Cl, Br, F, I), NO₂, OC(O)O(Ci-₄alkyl), OC(O)O(C₁._it alkyl), OC(O)O(C₂_₄ alkynyl), OC(O)O(C₂-₄ alkenyl), 0C_x-₄ haloalkyl, O (aminoacyl), 0(C!-₄ acyl), 0(Ci-₄ rent), 0(C₂.₄ alkenyl), S(Ci-₄acyl), S(Ci-₄ rent), S(C₂-₄ alkynyl), S(C₂.₄ alkenyl), SO(Ci-₄ acyl), SO(Ci-₄ alkyl), SO(C₂_₄ alkynyl), SO(C₂.₄alkenyl), SO₂(Ci-₄ acyl), SO₂(Ci-₄ rent), SO₂(C₂_₄alkynyl), SO₂(C₂.₄ alkenyl), OS(O)₂(Ci-₄ acyl), OS(O)₂(Ci-₄ rent), OS(O)₂(C₂_₄ alkenyl), NH₂, NH(Ci-₄alkyl), NH(C₂-₄ alkenyl), NH(C₂-₄ alkynyl), NH(Ci-₄acyl), N(Ci-₄ rent)₂, or N(Ci-₄ acyl)₂;

(i) R⁷, R⁸,R⁹ are independently H, F, Cl, Br, I, OH,

OR', SH, SR', NH₂, NHRA¹, NR'₂, lower alkyl, halogenated lower alkyl (F, Cl, Br, I), C lower alkenyl₂-C_yes, CO₂H, CO₂R', CONH_2z CONHR', CONR'_2nd where R' is a Ci-₂₀rent; a Ci-₂₀ cycloalkyl; a C₂-C₆ alkenyl, a C₂-C₆alkynyl.

The second aspect of the first modality is directed to the compound represented by formula 1-1: where (a) R¹ is hydrogen, n-alkyl or a substituted or unsubstituted phenyl, where the substituted phenyl substituent is at least one of C₃-₃ rent, a Ci-₃alkoxy, F, Cl, Br, I, nitro, cyano and a Ci-₃ haloalkyl;

(b) R2 is hydrogen or CH₃;

(c) R^3rd and R^3b are independently (i) R^3rd is hydrogen and R^3b and R² together they are (CH₂)n so that we form

36/967 a cyclic ring that includes N and C atoms together (v) R^3b is hydrogen and R^3rd and R² together they are (CH₂)n so that they form a cyclic ring that includes N and C atoms together, where c is 1 to 6, dé0a2, eé0a3, f is 3 to 5, n is 2 to 4, and where R³' is independently hydrogen or Ci-_Yes rent and R³ is -OR' or —N(R³ )2); (vi) R^3rd is H and R^3b 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, 10 CH₂((4'-OH)-Ph), CH₂SH, or lower cycloalkyl; or (viii)

R^3rd is CH₃, CH(CH₃)₂, CH₂CH(CH₃)₂, CH(CH₃) CH₂CH_3z CH₂Ph, CH₂indol-3-yl, -CH₂CH2SCH₃, CH₂CO₂H, CH₂C(O)NH₂, CH₂CH₂COOH, CH₂CH₂C(O)NH₂, CH₂CH₂CH₂CH₂NH₂, -CH₂CH₂CH2NHC(NH)NH₂, ch₂imidazol-4-yl, CH₂OH, CH(OH)CH₃, CH₂ ( (4'-OH)-Ph) , or CH₂SH and 15 R^3b is H;

(d) R⁴ is hydrogen, CH₃, And,^xYes,ⁿYes,ⁿBu, 2-butyl, hfiu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl20 piperidin-4-yl, lower haloalkyl, di(lower alkyl)amino-lower alkyl, or aminoacyl;

(e) R5 is H, CN, CH₃, OCH₃, CH₂OH, CH₂ (halo) , such as CH₂F, n₃, ch₂cn, CH₂N₃, CH₂NH₂, CH₂NHCH₃, CH₂N(CH₃)₂, halogen, including F, Cl, Br, or I, with the proviso that when X is OH, the base is a cytosine and R^and is H, R^yes can't 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),

37/967

NH(C(O)CH₃), N(CH₃)₂, N(C(0)CH₃)₂, or O(aminoacyl);

(i) R⁷ and R® are independently H, F, Cl, Br, I, OH, OCH₃, SH, SCH₃, NH₂, NHCH₃, N(CH₃)₂, CH₃, CH₃__whatX_what, where X is F, Cl, Br, or I eq is 1 to 3, vinyl, CO₂H, CO₂CH₃, CONH₂, CONHCH₃, OR WITH(CH₃)₂; and (j) R⁹ is selected from OH, OCH₃, SH, SCH₃, NH₂, NHCH₃, N(CH₃)₂, OC(O) (Cl-20 alkyl), which includes, among others, OC(Ο) (CH₂) _yesCH₃, NHC(O) (Cl-20 alkyl), which includes, but is not limited to, NHC(O) (CH₂)_YesCH_3; and N(C(O) (CH₂)_yesCH₃)₂, which includes, among others, N(C(O) (CH₂)_yesCH₃)₂, where s is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, and 19.

The third aspect of the first modality is directed to the compound represented by the formula 1-1:

where (a) R¹ is hydrogen, n-alkyl or a substituted or unsubstituted phenyl, where the substituent of the substituted phenyl is at least one of CH₃, OCH₃, F, Cl, Br, I, nitro, cyano and a CH₃._whatX_what, where XéF, Cl, Brouleqél3 ;

(b) R2 is hydrogen or CH₃;

(c) R^3rd is H and R^3b 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 R^3rd is CH₃, CH(CH₃)₂, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH_3z CH₂Ph, CH₂-indol-3yl, -CH₂CH₂SCH₃, CH₂CO₂H, CH₂C(O)NH₂, ch₂ch₂coo, ch₂ch₂c(o)nh₂, ch₂ch₂ch₂ch₂nh₂, -ch₂ch₂ch₂nhc(nh)nh₂, ch₂imidazol-4-yl, CH₂OH, CH(OH)CH₃,

CH₂ ( (4 '-OH)-Ph) , CH₂SH, or

38/967 lower cycloalkyl and R^3b is H;

(d) R4 is hydrogen, CH₃, Et, ^r,ⁿYes,ⁿBu, 2-butyl,^fcBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, 5 N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, halolower alkyl, di(lower alkyl)amino-lower alkyl or aminoacyl;

(e) R⁵ is H, CN, CH₃, OCH₃, CH₂OH, CH₂ (halo) , such as CH₂F, n₃, CH₂CN, CH₂N₃, CH₂NH₂, CH₂NHCH₃, CH₂N(CH₃)₂, halogen, including F, Cl, Br, or I, with the proviso that when X is OH, the base is a cytosine and R⁶ is H, 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, oh₃, 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_qX_what, where X 20 is F, Cl, Br, ouleqéla3, vinyla, CO₂H, CO₂CH₃, CONH₂, CONHCH₃, or WITH(CH₃)2, where R' is Ci-₂₀ rent; Ci-₂₀ cycloalkyl; C₂-C₆ alkenyl, C₂-C₆ alkynyl'; and (j) R 9 is selected from OH, OCH₃, SH, SCH₃, NH₂,

NHCH₃, N(CH₃)₂, 0C(0)(Cl-20 alkyl), which includes, among others, 0C(0) (CH₂)_YesCH₃, NHC(O) (Cl-20 alkyl), which includes, but is not limited to, NHC(O) (CH₂)_YesCH₃, and N(C(O) (CH₂)_YesCH₃)₂, which includes, among others, N(C(O) (CH₂)_YesCH₃)₂, where s is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, and 19.

The fourth aspect of the first modality is

39/967 addressed to the compound represented by formula 1-2:

PA

<img file="BRPI0809654A2_D0006.tif" />

(a) R¹ is hydrogen, methyl, ethyl, n-propyl, ipropyl or a substituted or unsubstituted phenyl, where the substituent of the substituted phenyl is at least one of CH₃, OCH₃, F, Cl, Br, I, nitro, cyano and a CH₃.qXg, where X is F, Cl, Br or I eq is 1-3;

(b) R2 is hydrogen or CH₃ ;

(c) R^3rd is H and R^3b 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 R^3rd is CH₃, CH(CH₃)₂, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, CH₂Ph, CH₂-indol-3yl, -ch₂ch₂school₃, ch₂with₂h, CH₂C(O)NH₂, CH₂CH₂COOH, CH₂CH₂C(O)NH₂, CH₂CH₂CH₂CH2NH₂, -CH₂CH₂CH2NHC(NH)NH₂, ch₂imidazol-4-yl, CH₂OH, CH(OH)CH₃, CH₂ ( (4 '-OH)-Ph) , CH₂SH, or lower cycloalkyl and R^3b is H;

(d) R⁴ is hydrogen, Ci-io is alkyl, Ci-₁₀ alkyl optionally substituted by a lower alkyl, alkoxy

40/967 or halogen, Ci-i₀ haloalkyl, C₃-i₀ cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aminoacyl, di(lower alkyl)amino-lower alkyl, aryl, such as phenyl, heteroaryl, such as, pyridinyl, substituted aryl, or substituted heteroaryl;

(e) R⁵ is H, CN, CH3, OCH3, CH2OH, CH2F, N3, CH2CN, CH2N3, CH2NH2, CH2NHCH3, CH2N(CH3)2, halogen, including F, Cl, Br, or I, with the proviso that when X is OH, the base is a cytosine and R⁶ is H, 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)_2z 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, where X is F, Cl, Br, ouleqéla3, vinyla, CO₂H, CO₂CH₃, CONH₂, CONHCH₃ or WITH(CH₃)₂, where R' is Ci_₂₀ rent; Ci-₂₀cycloalkyl; C₂-C₆ alkenyl, C₂-C₆ alkynyl'; and (j) R⁹ is selected from OH, OCH₃, SH, SCH₃, NH₂, NHCH₃, N(CH₃)₂, 0C(0)(Cl-20 alkyl), which includes, among others, OC(O) (CH₂) _yesCH₃, NHC(O) (Cl-20 alkyl), which includes, but is not limited to, NHC(0) (CH₂)_YesCH₃, and N (C (O) (CH₂) _YesCH3) CH2, which includes, among others, N(C(O) (CH₂)_YesCH₃)₂, where s is an integer selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, and 19.

The fifth aspect of the first modality is directed to the compound represented by formula 1-2: where (a) R¹ is hydrogen, methyl, ethyl, n-propyl, i41/967 propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl; r (b) R2 is hydrogen or CH₃;

(c) R^3rd is H and R^3b is H, CH_3/ CH(CH₃)₂, CH₂CH(CH₃)₂,

CH(CH₃)CH₂CH₃, CH₂Ph, CH₂-indol-3-yl, -CH₂CH₂SCH₃, CH₂CO₂H, CH₂C(O)NH₂, ch₂ch₂coo, 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, And,^xYes,ⁿYes,ⁿBu, 2-butyl,^fcBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, halolower alkyl, di(lower alkyl)amino-lower alkyl or aminoacyl;

(e) R⁵ is H, CN, CH₃, OCH₃, CH₂OH, CH₂F, halogen, including 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, 20 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-gX_what, where X is F, Cl, Br, or I eq is 1 to 3, vinyl, CO₂H, CO₂CH₃, CONH₂, CONHCH3 or CON(CH₃)₂, where R' is Ci-₂₀ rent; Ci-₂₀ cycloalkyl; C₂-C₆ alkenyl, C₂-C₆ alkynyl'; and (j) R⁹ is selected from OH, OCH₃, SH, SCH₃, NH₂,

NHCH₃, N(CH₃)₂, OC(O) (Ci-20 alkyl), which includes, among others, OC(O) (CH₂) _yesCH₃ , NHC(O)(Ci-₂₀ alkyl), which includes, among others, NHC(O) (CH₂)_YesCH₃, and N(C(O) (CH₂)_YesCH₃)₂, which includes, among others, N(C(O) (CH₂)_YesCH₃)₂, where s is a number

42/967 integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18 and 19.

The sixth aspect of the first modality is directed to the compound represented by formula 1-2:

where (a) R¹ is hydrogen, methyl, ethyl, n-propyl, ipropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b) R² is hydrogen or CH₃;

(c) R^3rd is H and R^3b is H, CH₃, CH(CH₃)₂, CH₂CH(CH₃)₂,

CH (CH₃) CH₂CH₃, CH₂Ph, or lower cycloalkyl;

(d) R⁴ is hydrogen, Ci-i₀ rent, Ci-i₀ alkyl optionally substituted by a lower alkyl, alkoxy or halogen, Ci-₁₀ haloalkyl, C₃-i₀ cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aminoacyl, di(lower alkyl)amino-lower alkyl, aryl, such as phenyl, heteroaryl, such as, pyridinyl, substituted aryl, or substituted heteroaryl;

(e) R^yes 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, 25 CH₃_qXq, where X is F, Cl, Br or I eq is 1 to 3, vinyl, CO₂CH₃, CONHs, CONHCH₃ OR WITH(CH₃)₂; and (j) R⁹ is selected from OH, OCH₃, SH, SCH₃, NH₂, NHCH₃, N(CH₃)₂, OC(O) (Ci-20 alkyl), which includes, among others, OC(O) (CH₂) _yesCH₃ , NHC(O)(Ci-₂₀ alkyl), which includes, among others, NHC (0) (CH₂) _yesCH₃ , and N (C (O) (CH₂) _YesCH₃) ₂, that

43/967 includes, among others, N (C (O) (CH₂) _YesCH₃) ₂, where s is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, and 19.

The seventh aspect of the first modality is directed to the compound represented by formula 1-2:

where (a) R¹ is hydrogen, methyl, ethyl, n-propyl, ipropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b) R² is hydrogen;

(c) R^3rd is H and R^3b is H, CH₃, CH(CH₃)₂, CH₂CH(CH₃)₂, CH (CH₃) CH₂CH₃, CH₂Ph, or lower cycloalkyl;

(d) R⁴ is hydrogen, CH₃, And,^xYes,ⁿYes,ⁿBu, 2-butyl,^fcBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methylpiperidin-4-yl, halolower alkyl, 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-qX_what, where X is F, Cl, Br or I eq is 1 to 3, vinyl, CO₂CH₃, CONH₂ , CONHCH3 or CON (CH₃) ₂; and (j) R⁹ is selected from OH, OCH₃, SH, NH₂, NHCH₃, N(CH₃)₂, OC(O) (Ci-20 alkyl), which includes, among others, OC(O) (CH₂) _yesCH₃ , NHC(O) (Cx-20 alkyl), which includes, but is not limited to, NHC(O) (CH₂)_yesCH₃, and N (C (O) (CH₂) _yes) CH₃) ₂, which includes, among others, N(C (O) (CH₂) _YesCH₃) ₂, where s is an integer

44/967 selected from 1, 2, 3, 4, 5, 6, Ί, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18 and 19.

The eighth aspect of the first modality is directed to the compound represented by formula 1-2:

where (a) R¹ is hydrogen, methyl, phenyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b) R² is hydrogen;

(c) R^3rd is H and R^3b is H, CH₃, CH(CH₃)₂, CH₂CH(CH₃)₂, CH(CH₃) CH₂CH₃, CH₂Ph, or lower cycloalkyl;

(d) R⁴ is hydrogen, CH₃, And,^xYes,ⁿYes,ⁿBu, 2-butyl,^fcBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methylpiperidin-4-yl, halolower alkyl, 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-gXg, where X is F, Cl, Br or I eq is 1 to 3, vinyl, CO₂CH₃, CONH₂, CONHCH₃ or WITH(CH₃)₂;

(j) R⁹ is selected from OH, OCH₃, SH, NH₂, NHCH₃, N(CH₃)₂, OC (O) (Ci-₂₀ alkyl), which includes, among others, OC (O) (CH₂) _yesCH₃ , NHC(O) (Ci-20 alkyl), which includes, but is not limited to, NHC(O) (CH₂)_YesCH₃, and N (C(O) (CH₂) s) CH₃) ₂, which includes, among others, N (C (O) (CH₂) _YesCH₃) ₂, where s is an integer selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,

13, 14, 15, 16, 17, 18 and 19.

45/967

A second embodiment of the invention is directed to the compound represented by formula I in which the base is a structure represented by formula b above, where R¹, R², R^3rd, R^3b, R⁴, R⁵, R⁶, X, Y, R⁷ and R⁸ are defined in the Summary of the Invention section above.

A first aspect of the second modality is directed to the compound represented by formula 1-3:

<img file="BRPI0809654A2_D0007.tif" />

where (a) RI is hydrogen, n-alkyl; branched alkyl; cycloalkyl; or aryl, which includes, but is not limited to, phenyl or naphthyl, where phenyl or naphthyl is optionally substituted with at least one of Cx-g alkyl, C₂.₆alkenyl, C₂-₆ alkynyl, Ci-₆ alkoxy, F, Cl, Br, I, nitro, cyano, Ci-6 haloalkyl, -N(R¹')2, Ci-6 acylamino, -NHSO2Ci-6 alkyl, -SO2N(R¹')2, COLOR¹”, and -SO2Cx-6 alkyl; (RI' is independently hydrogen or alkyl, which includes, but is not limited to, Cx-20 alkyl, Ci-i0 alkyl, or Ci-6 alkyl, Rl is -OR' or -N(R¹')2);

(b) R2 is hydrogen or CH₃;

(c) R3a and R3b are (i) independently selected from hydrogen, C1-6 alkyl, cycloalkyl, - (CH₂) _c (NR³') ₂, C1-6 hydroxyalkyl, -CH₂SH, - (CH₂) 2S (O) dMe,

46/967 (CH2)3NHC(=NH)NH2, (1H-indol-3-yl) methyl, (1H-imidazol-4iDmethyl, - (CH2) eCOR³, aryl and aryl Cx-3 alkyl, said aryl groups optionally substituted by a group selected from hydroxyl, C1-10 alkyl, Cl-6 alkoxy, halogen, nitro and cyano; (ii) R^3rd and R^3b both are C 1-6 alkyl; (iii) R^3rd and R^3b together they are (CH₂)f so as to form a spiro ring; (iv) R^3rd is hydrogen and R^3b and R² together they are (CH2)n so as to form a cyclic ring that includes the adjacent atoms N and C (v) R^3b is hydrogen and R^3rd and R²together are (CH2)n so as to form a cyclic ring that includes the adjacent atoms N and C, where c is 1 to 6, déOa 2, eé0a3, f is 2 to 5, n is 2 to 4, and where R³' is independently hydrogen or Ci-β alkyl and R³ is -OR' or -N(R³')₂); (vi) R^3rd H and R^3b 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)NH2z CH2-imidazol-4-yl, CH2OH, CH(OH)CH3, CH2( (4'-OH)-Ph) , CH2SH, or lower cycloalkyl; or (viii) R^3rd 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 and R^3b is H, where R³' is independently hydrogen or alkyl, which includes, but is not limited to, C1-20 alkyl, C1-10 alkyl, or C1-6 alkyl, R³ is -OR' or -N(R³')2);

(d) R⁴ is hydrogen, Ci-χο is alkyl, Ci-i₀ alkyl optionally substituted by a lower alkyl, alkoxy or halogen, Cj.-₁₀ haloalkyl, C₃-i₀ cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aminoacyl,

47/967 di(lower alkyl)amino-lower alkyl, aryl, such as phenyl, heteroaryl, such as, pyridinyl, substituted aryl, or substituted heteroaryl;

(e) R⁵ is H, a lower alkyl, CN, vinyl, O(lower alkyl), hydroxyl lower alkyl, that is, (CH₂)_POH, where p is 1-6, including hydroxyl methyl (CH₂OH) , CH₂F, N₃, CH₂CN, CH₂NH₂, CH₂NHCH₃, CH₂N(CH₃)₂, alkyne (optionally substituted), or halogen, including F, Cl, Br, or I, with the proviso that when X is OH, base is cytosine and R⁶ is H, R⁵ can't be N₃ and when X is OH, R^yes is

CH₃ or CH₂F and 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, Ci-4 alkyl, C₂.₄ alkenyl, C₂.₄alkynyl, vinyl, N₃, CN, Cl, Br, F, I, NO₂, OC(O)O(Ci-₄alkyl), OC(O)O(Ci-₄ alkyl), OC(O)O(C₂.₄ alkynyl), OC(O)O(C₂-₄ alkenyl), OCi-₁₀ haloalkyl, O (aminoacyl), O(Ci-₁₀ acyl), 0(Ci-₄ rent), 0(C₂_₄ alkenyl), S(01.-4 acyl), S(Ci-₄ rent), S (C₂_₄ alkynyl), S(C₂.₄ alkenyl), SO(Ci-₄ acyl), SO(Ci-₄ alkyl), SO(C₂-₄ alkynyl), SO(C₂.₄alkenyl), SO₂(C₁_₄ acyl), SO₂(Ci-₄ rent), SO₂(C₂.₄alkynyl), SO₂(C₂.₄ alkenyl), OS(O)₂(Ci-₄ acyl), OS(O)₂(C_W rent), OS(O)₂(C₂.₄ alkenyl), NH₂, NH(Ci-₄alkyl), NH(C₂_₄ alkenyl), NH(C₂-₄ alkynyl), NH(Ci-₄acyl), N(Ci-₄ rent)₂, N(C1-18 acyl)₂, in which alkyl, alkynyl, alkenyl and vinyl are optionally substituted by N₃, CN, one to three halogens (Cl, Br, F, I), N0₂, C(O)O(Ci-₄ alkyl), C(O)O(Ci-₄ alkyl), C(O)O(C₂.₄alkynyl), C(O)O(C₂.₄ alkenyl), 0(C_x-4 acyl), 0(Ci-₄alkyl), O(C₂.₄ alkenyl), S(Ci-₄ acyl), S(Ci-₄ rent),

48/967

S(C₂-4 alkynyl) , S(C₂-₄ alkenyl), SO(Ci-₄ acyl) , SO(Ci-₄alkyl), SO(C₂.₄ alkynyl), SO(C₂.₄ alkenyl), SO₂(Ci-₄acyl), SO₂(Ci-₄ rent), SO₂(C₂-₄ alkynyl), SO₂(C₂.₄alkenyl), OS(O)₂(Ci-₄ acyl), OS (0)₂ (Ci-₄ rent), 5 OS(O)₂(C₂.₄ alkenyl), NH₂, NH(C_X.₄ alkyl), NH(C₂-₄ alkenyl), NH(C₂_₄ alkynyl), NH(C_X.₄ acyl), N(C_X.₄rent)₂, N(C_x-₄ acyl)₂;

(i) R⁷ and R⁸ are independently H, F, Cl, Br, I, OH, OR', SH, SR', NH₂, NHR', NR'₂, lower alkyl, halogenated lower alkyl 10 (F, Cl, Br, I) , C lower alkenyl₂-C₆, CO₂H, CO₂R', CONH₂, CONHR', CONR'₂, where R' is a C_X-₂₀rent; a C_X.₂₀ cycloalkyl; a C₂-C₆ alkenyl, a C₂-C_yesalkynyl.

The second aspect of the second embodiment is directed to the compound represented by formula 1-3: where (a) R1 is hydrogen, n-alkyl, or aryl, which includes, but is not limited to, phenyl or naphthyl, where phenyl or naphthyl is optionally substituted by at least one 20 Ci-6 alkyl, C_x.₆ alkoxy, F, Cl, Br, I, nitro, cyano, C_x.₆haloalkyl;

(b) R² is hydrogen or CH₃;

(c) R^3rd and R^3b are independently (i) R^3rd is hydrogen and R^3b and R² together they are (CH2)n so that they form a cyclic ring that includes the atoms N and C together (v) R^3b is hydrogen and R^3rd and R² together they are (CH2)n so that they form a cyclic ring that includes N and C atoms together, where c is 1 to 6, dé0a2, eé0a3, f is 3 to 5, né2a4, and where R³' is independently hydrogen or Cx.6 alkyl and R³ is -OR' or 30 -N(R³')2); (vi) R^3rd is H and R^3b is H, CH₃, CH(CH₃)₂, CH₂CH(CH₃)₂,

49/967

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((4¹-OH)-Ph), CH2SH, or lower cycloalkyl; or (viii) R^3rd is CH3, CH(CH₃)₂, CH₂CH(CH₃)₂, CH (CH₃) CH₂CH₃, CH₂Ph, CH₂indol-3-yl, -CH₂CH₂SCH₃, CH₂CO₂H, CH₂C(O)NH₂, CH₂CH₂COOH, ch₂ch₂c(O)NH₂, ch₂ch₂ch₂ch₂nh₂, -ch₂ch₂ch₂nhc(nh)nh₂, ch₂imidazol-4-yl, CH₂OH, CH(OH)CH_3z CH₂ ( (4'-OH)-Ph) , or CH₂SH and R^3b is H;

(d) R⁴ is hydrogen, Ci-i₀ rent, Ci-i₀ alkyl optionally substituted by a lower alkyl, alkoxy or halogen, Ci-₁₀ haloalkyl, C₃.₁₀ cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aminoacyl, di(lower alkyl)amino-lower alkyl, aryl, such as phenyl, heteroaryl, such as, pyridinyl, substituted aryl, or substituted heteroaryl;

(e) R⁵ is H, CN, CH₃, vinyl, OCH₃, OCH₂CH₃, CH₂OH, CH₂ (halo) , such as CH₂F, N₃, CH₂CN, CH₂N₃, CH₂NH₂, CH₂NHCH₃, CH₂N(CH₃)₂, halogen, including F, Cl, BR or I;

(f) R^yes 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, Ci-4 alkenyl, vinyl, N₃, CN, Cl, Br, F, I, O(Ci-₆ acyl) , O(Ci-₄ rent), NH₂, ΝΗ(Ο_X.₄ alkyl), NH(C₂-4 alkenyl), NH(C₂.₄ alkynyl) , NH(Ci-₄ acyl), N(Ci-₄rent)₂, N(Ci-i₈ acyl)₂, where alkyl, alkynyl, alkenyl and vinyl are optionally substituted by N₃, CN, one to three halogens (Cl, Br, F, I), NO₂, OC(O)O(Ci-₄alkyl), OC (0)0(0^^ alkyl), OC(O)O(C₂.₄ alkynyl), OC(O)O(C₂-₄ alkenyl), OCx-io haloalkyl, O (aminoacyl), 0(Ci-₄ acyl), 0(Ci-₄ alkyl), O(C₂.₄ alkenyl), S(Ci-₄

50/967 acyl), S(Ci-4 alkyl), S(C₂-₄ alkynyl), S(C₂.₄ alkenyl), SO(Ci-₄ acyl), SO(C_x-₄ alkyl), SO(C₂-₄ alkynyl), SO(C₂-₄alkenyl), SO₂(C_x-₄ acyl), SO₂(Cx-₄ rent), SO₂(C₂.₄alkynyl), SO₂(C₂.₄ alkenyl), OS(O)₂(Ci-₄ acyl), OS (0)₂ (Ci-₄ rent), OS(O)₂(C₂_₄ alkenyl), NH₂, NH(Ci-₄alkyl), NH(C₂-₄ alkenyl), NH(C₂.₄ alkynyl), ΝΗ(Οχ_₄acyl), N(Οχ-₄ rent)₂, or N(C_X-₄ acyl)₂;

(i) R⁷ and R⁸ are independently H, F, Cl, Br, I, OH, OR', SH, SR', NH₂, NHR', NR'₂, lower alkyl, halogenated lower alkyl (F, Cl, Br, I), C lower alkenyl₂-C₆, CO₂H, CO₂R', CONH_2z CONHR', CONR'₂, where R' is a Ci-₂₀rent; a Cx-₂the cycloalkyl; a C₂-C₆ alkenyl, a C₂-C₆alkynyl.

The third aspect of the second modality is directed to the compound represented by formula 1-3:

where (a) R¹ is hydrogen, n-alkyl or a substituted or unsubstituted phenyl, where the substituent of the substituted phenyl is at least one of Ci-₃ rent, a Ci-₃alkoxy, F, Cl, Br, I, nitro, cyano and a C_x-₃ haloalkyl;

(b) R² is hydrogen, CH3-R^3rd or R^3b or R² together they are (CH2)₃ so as to form a cyclic ring that includes the adjacent atoms N and C, C (O) CR^3rdR^3bNHR^x, where n is 2 to 4 and R¹, R^3rd and R3b are as defined herein;

(c) R^3rd and R^3b are independently (i) R^3rd is hydrogen and R^3b and R² together they are (CH2)n so that they form a cyclic ring that includes the atoms N and C together (v) R^3b is hydrogen and R^3rd and R² together they are (CH2)_n so that they form a cyclic ring that includes N and C atoms together, where c is 1 to 6, dé0a2, eé0a3, f is 3 to 5, né2a4, and where R³'

51/967 is independently hydrogen or Ci-₆ rent and R³ is -OR' or —N(R³')2); (vi) R^3rd is H and R^3b is H, CH3/ CH(CH₃)₂, CH₂CH(CH₃)_2zCH(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) R^3rd is CH3, CH(CH3)2z CH2CH(CH3)2, CH (CH3) CH2CH3, CH2Ph, CH2indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C(O)NH2, CH2CH2COOH, CH2CH2C(O)NH2, ch2ch2ch2ch2nh2, -CH2CH2CH2NHC(NH)NH2, ch2imidazol-4-yl, CH2OH, CH(OH)CH3, CH2 ( (4¹-OH)-Ph) or CH2SH and R^3b is H;

(d) R⁴ is hydrogen, CH₃, And,^xYes,ⁿYes,ⁿBu, 2-butyl,^bBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methylpiperidin-4-yl, halolower alkyl, di(lower alkyl)amino-lower alkyl;

(e) R^yes is H, CN, CH₃, vinyl, OCH₃, CH₂OH, CH2, CH2F(halo), such as N₃, CH₂CN, CH₂N₃, CH₂NH₂, CH₂NHCH₃, CH₂N(CH₃)₂, halogen, including F, Cl, BR or I;

(f) R⁶ is H, CH₃, CH₂F, CHF₂, CF_3z 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 or O (aminoacyl);

(i) R⁷ and R⁸ are independently H, F, Cl, Br, I, OH, OCH₃, SH, SCH₃, NH₂, NHCH₃, N(CH₃)_2z CH₃, CH₃._whatXg, where X is F, Cl, Br, ouleqéla3, vinyla, CO₂H, CO₂CH₃, CONH₂, CONHCH₃ , or WITH (CH₃) 2 .

The fourth aspect of the second modality is

52/967 directed to the compound represented by formula 1-3: where (a) R¹ is hydrogen, n-alkyl or a substituted or unsubstituted phenyl, where the substituent of the substituted phenyl is at least one of CH₃, OCH₃, F, Cl, Br, I, nitro, cyano and a CH₃._whatX_what, where X is F, Cl, Br or I eq is 13 ;

(b) R² is hydrogen or CH₃;

(c) R^3rd is H and R^3b 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 R^3rd is CH3, CH(CH₃)₂, CH₂CH(CH₃)₂, CH(CH₃) CH₂CH₃, CH₂Ph, CH₂-indol-3yl, -CH₂CH₂SCH₃, ch₂with₂h, CH₂C(O)NH₂, ch₂ch₂cooh, CH₂CH₂C(O)NH₂, ch₂ch₂ch₂ch₂nh₂, -ch₂ch₂ch₂nhc(nh)nh₂, ch₂imidazol-4-yl, CH₂OH, CH(OH)CH₃, CH₂ ((4'-OH)-Ph) , CH2SH, or lower cycloalkyl and R^3b is H;

(d) R⁴ is hydrogen, CH₃, And,¹Yes,ⁿYes,ⁿBu, 2-butyl,^fcBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methylpiperidin-4-yl, halolower alkyl, di(lower alkyl)amino-lower alkyl;

(e) R⁵ is H, CN, CH₃, vinyl, OCH₃, CH₂OH, CH2, CH2F(halo), such as N₃, CH₂CN, CH₂N₃, CH₂NH₂, CH₂NHCH₃, CH₂N(CH₃)₂, halogen, including F, Cl, BR or I;

(f) R^yes 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,

53/967

OC(O)CH₃, OCH3, NH₂, NHCH₃, NH(vinyl), NH(acetyl), NH(C(O)CH₃), N(CH₃)₂, N(C(O)CH₃)₂ OR 0(aminoacyl) ;

(i) R⁷ and R⁸ are independently H, F, Cl, Br, I, OH, OCH₃, SH, SCH₃, NH_2z NHCH₃, N(CH₃)₂, CH_3/ CH₃__whatX_what, where X 5 is F, Cl, Br, oleqela3, vinyl, CO₂H, CO₂CH₃, CONH₂, CONHCH₃ or WITH(CH₃)₂, where R' is C^o alkyl; Ci-₂₀cycloalkyl; C₂-C₆ alkenyl, C₂-C₆ alkynyl'; and

The fifth aspect of the second modality is directed to the compound represented by formula 1-4:

R^

<img file="BRPI0809654A2_D0008.tif" />

YX

1-4 where (a) Rl is hydrogen, methyl, ethyl, n-propyl, i20 propyl or a substituted or unsubstituted phenyl, where the substituent of the substituted phenyl is at least one of CH₃, OCH₃, F, Cl, Br, I, nitro, cyano and a CH₃__whatX_what, where X is F, Cl, Br or I eq is 1 - 3;

(b) R² is hydrogen or CH₃;

(c) R^3rd is H and R^3b 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 R^3rd is 30 CH₃, CH(CH₃)₂, CH₂CH(CH₃)₂, CH(CH₃) CH₂CH₃, CH₂Ph, CH₂-indole-354/967 yl, -CH₂CH₂SCH₃, CH₂CO₂H, CH₂C(O)NH₂, CH₂CH₂COOH, CH₂CH₂C(O)NH₂, CH₂CH₂CH₂CH₂NH₂, -CH₂CH₂CH₂NHC(NH)NH₂, CH₂imidazol-4-yl, CH₂OH, CH(OH)CH₃, CH₂ ((4'-OH)-Ph) , CH₂SH, or lower cycloalkyl and R^3b is H;

(d) R⁴ is hydrogen, CH₃, And,^xYes,ⁿYes,ⁿBu, 2-butyl,^fcBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methylpiperidin-4-yl, halo-lower alkyl, di(10-lower alkyl)amino-lower alkyl;

(e) R^yes is H, CN, CH₃, vinyl, OCH₃, CH₂OH, CH₂F, N3 (halo), such as CH₂CN, CH₂N₃, CH₂NH₂, CH₂NHCH₃, CH₂N(CH₃)₂, halogen, including 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, OCH_3z NH₂, NHCH₃, NH(vinyl), NH(acetyl), NH(C(O)CH₃), N(CH₃)₂, N(C(0)CH₃)₂ or 0 (aminoacyl);

(i) R⁷ and R⁸ are independently H, F, Cl, Br, I,

0 OH, OH₃, SH, SCH₃, NH₂, NHCH₃, N(CH₃)₂, CH₃, CH₃.qX_what, where X is F, Cl, Br, or I eq is 1 to 3, vinyl, CO₂H, CO₂CH₃, CONH₂, CONHCH3 or CON(CH₃)₂, where R' is C_X.₂₀ rent; Ci-₂₀cycloalkyl; C₂-C_and alkenyl, C₂-C₆ alkynyl',· and

The sixth aspect of the second modality is directed 25 to the compound represented by formula 1-4:

where (a) R¹ is hydrogen, methyl, ethyl, n-propyl, ipropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b) R² is hydrogen or CH₃;

55/967 (OR)^3rd is H and R^3b is H, CH₃, CH(CH₃)₂, CH₂CH(CH₃)_2zCH(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;

(d) R⁴ is hydrogen, CH₃, And,¹Yes,ⁿYes,ⁿBu, 2-butyl,^fcBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methylpiperidin-4-yl, halolower alkyl, di(lower alkyl)amino-lower alkyl;

(e) R^yes is H, CN, CH₃, OCH₃, CH₂OH, CH₂F, halogen, including 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, OH₃, SH, SCH₃, NH₂, NHCH₃, N(CH₃)₂, CH₃, CH₃._whatX_what, where X is F, Cl, Br, or I eq is 1 to 3, vinyl, CO₂H, CO₂CH₃, CONH₂, CONHCH₃ or WITH(CH₃)₂, where R> is C^o alkyl; Ci-₂₀cycloalkyl; C₂-C₆ alkenyl, C₂-C_and alkynyl.

The seventh aspect of the second modality is directed to the compound represented by formula 1-4 where (a) R¹ is hydrogen, methyl, ethyl, n-propyl, ipropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b) R² is hydrogen or CH₃ ;

(c) R^3rd is H and R^3b is H, CH₃, CH(CH₃)₂, CH₂CH(CH₃)₂,

56/967

CH (CH₃) CH₂CH₃, CH₂Ph, or lower cycloalkyl;

(d) R⁴ is hydrogen, CH₃, And,⁴Yes,ⁿYes,ⁿBu, 2-butyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methylpiperidin-4-yl, halolower alkyl, 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 OUF;

(g) X is H, OH, F, OCH₃, F, Cl, Br, I, NH₂ orN (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_qXg, where X is F, Cl, Brouleqéla3, vinyla, CO₂CH₃, CONH₂, CONHCH₃ OR WITH(CH₃)₂;

The eighth aspect of the second modality is directed to the compound represented by formula 1-4:

where (a) R¹ is hydrogen, methyl, ethyl, n-propyl, ipropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b) R² is hydrogen;

(c) R^3rd is H and R^3b is H, CH₃, CH(CH₃)₂, CH₂CH(CH₃)₂, CH (CH₃) CH₂CH₃, CH₂Ph, or lower cycloalkyl;

(d) R⁴ is hydrogen, CH₃, And,^xYes,ⁿYes,ⁿBu, 2-butyl,^fcBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methylpiperidin-4-yl, halolower alkyl, di(lower alkyl)amino-lower alkyl;

57/967 (e) R⁵ is it 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.gXg, where XéF, Cl, Brouleqéla3, vinyla, CO₂CH₃, CONH₂, CONHCH₃ OR WITH(CH₃)₂.

The ninth aspect of the second modality is directed to the compound represented by formula 1-4 where (a) R¹ is hydrogen, methyl, phenyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b) R² is hydrogen;

(c) R^3rd is H and R^3b is H, CH₃, CH(CH₃)₂, CH₂CH(CH₃)₂, CH (CH₃) CH₂CH₃, CH₂Ph, or lower cycloalkyl;

(d) R⁴ is hydrogen, CH₃, And,^andYes,ⁿYes,ⁿBu, 2-butyl,^fcBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methylpiperidin-4-yl, halolower alkyl, 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, where XéF, Cl, Brouleqéla3, vinyla, CO₂CH₃, CONH₂, CONHCH-J or CON(CH₃)₂.

A third embodiment of the invention is directed to a compound represented by formula I in which the base is one

58/967 structure represented by formula c above, where R¹, R², R^3rd, R^3b, R⁴, R⁵, R⁶, X, Y, Z, R¹⁰, R^xxland R¹² are defined in the Summary of the Invention section above with the proviso that R¹¹not be H.

The first aspect of the third modality is directed to the compound represented by formula 1-5_Rw

<img file="BRPI0809654A2_D0009.tif" />

1-5 where (a) R¹ is hydrogen, n-alkyl; branched alkyl; cycloalkyl; or aryl, which includes, but is not limited to, phenyl or naphthyl, wherein phenyl or naphthyl is optionally substituted with at least one of Ci-6 alkyl, C2-6 alkenyl, C2.6 alkynyl, Ci-6 alkoxy, F, Cl, Br, I, nitro, cyano, Ci-6 haloalkyl, -N(R¹')2, Ci-_Yes acylamino, -NHSO₂Ci-_Yesrent, -SO₂N(R^X')2, COLOR¹, and -SO2Ci-₆ rent; (R¹' is independently hydrogen or alkyl, which includes, but is not limited to, CX-2o alkyl, Οχ.χο alkyl, or CX-6 alkyl, R^x -OR' or -N(R)¹’)2);

(b) R² is hydrogen or CH₃;

(c) R^3rd and R^3b are (i) independently selected from hydrogen, Ci_10 alkyl, cycloalkyl, - (CH2) c (NR³') 2, Ci-6 hydroxyalkyl, -CH₂SH, - (CH₂) ₂S(O)dMe, (CH₂)₃NHC(=NH)NH₂, (1H-indol-3-yl)methyl, (1H-imidazol-4-yl)methyl, - (CH₂)_andCOLOR³, aryl and aryl Cx-3 alkyl, the said

59/967 aryl groups optionally substituted by a group selected from hydroxyl, C1-i₀ rent, Ci-₆ alkoxy, halogen, nitro and cyano; (ii) R^3rd and R^3b both are Ci-₆rent; (iii) R^3rd and R^3b together they are (CH2)f so as to form a spiro ring; (iv) R^3rd is hydrogen and R^3b and R² together are (CH2) n so as to form a cyclic ring that includes the adjacent atoms N and C (v) R^3b is hydrogen and R^3rd and R²together they are (CH₂) _n so as to form a cyclic ring that includes adjacent atoms N and C, where c is 1 to 6, déOa 2, eé0a3, f is 2 to 5, n is 2 to 4, and where R³' is independently hydrogen or Ci-6 alkyl and R³ is -OR¹ or -N(R³')2); (vi) R^3rd is H and R^3b 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 ( (4¹-OH)-Ph) , CH2SH, or lower cycloalkyl; or (viii) R^3rd is CH3, -CH2CH3, CH(CH3)2, CH2CH(CH3)2, CH (CH3) CH2CH3z 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 and R^3b is H, where R³' is independently hydrogen or alkyl, which includes, but is not limited to, Ci-20 alkyl, Ci-i₀ alkyl, or Ci-β alkyl, R³ is -OR' or -N(R³')₂);

(d) R⁴ is hydrogen, Ci-io alkyl, Ci-i₀ alkyl optionally substituted by a lower alkyl, alkoxy or halogen, Ci-i₀ haloalkyl, C₃-i₀ cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aminoacyl, di(lower alkyl)amino-lower alkyl, aryl, such as phenyl, heteroaryl, such as, pyridinyl, aryl

60/967 substituted, or substituted heteroaryl;

(e) R⁵ is H, a lower alkyl, CN, vinyl, O(lower alkyl), hydroxyl lower alkyl, that is, (CH₂)_POH, where p is 1-6, including hydroxyl methyl (CH₂OH) , 5 CH₂F, N₃, CH₂CN, CH₂NH₂, CH₂NHCH₃, CH₂N(CH₃)₂, alkyne (optionally substituted), or halogen, including F, Cl, Br, or I, with the proviso that when X is OH, base is cytosine and R^yes is H, R⁵ it cannot be N3 and when X is OH, R⁶is CH3 or CH₂F and 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, Ci-4 alkyl, C₂_₄ alkenyl, C₂.₄ alkynyl, vinyl, N₃, CN, Cl, Br, F, I, NO₂, OC(O)O(C_X.₄alkyl), OC(O)O(C_X.₄ alkyl), OC(O)O(C₂.₄ alkynyl), 15 OC(O)O(C₂_₄ alkenyl), OC_x__xox haloalkyl, O (aminoacyl),

0(Ci-io acyl), O(C_X_₄ alkyl), O(C₂_₄ alkenyl), S(C_X.₄acyl), S(C_X.₄ rent), S(C₂-₄ alkynyl), S(C₂_₄ alkenyl), SO(Ci-₄ acyl), SO(C_X_₄ alkyl), SO(C₂.₄ alkynyl), SO(C₂_₄alkenyl), SO₂(C_X.₄ acyl), SO₂(C_x-₄ rent), SO₂(C₂-₄ alkynyl), SO₂(C₂-₄ alkenyl), OS(O)₂(C_X.₄ acyl), OS(O)₂(C_X.₄ rent), OS(O)₂(C₂_₄ alkenyl), NH₂, NH(C_X.₄alkyl), NH(C₂.₄ alkenyl), NH(C₂.₄ alkynyl), NH(C_X.₄acyl), N(C_x_₄ rent)₂, N(C1-18 acyl)₂, wherein alkyl, alkynyl, alkenyl and vinyl are optionally substituted by N₃, CN, one to three halogens (Cl, Br, F,

I), NO₂, C(O)O(C_x.₄ alkyl), C(O)O(C_X_₄ alkyl), C(O)O(C₂.₄alkynyl), C(O)O(C₂_₄ alkenyl), O(C_X_₄ acyl), O(C_X.₄alkyl), O(C₂.₄ alkenyl), S(C_X_₄ acyl), S(C_X_₄ rent), S(C₂.₄ alkynyl), S(C₂-₄ alkenyl), SO(C_X.₄ acyl), SO(C_X_₄30 alkyl), SO(C₂.₄ alkynyl), SO(C₂.₄ alkenyl), SO₂(C_X_₄

61/967 acyl) , SO₂ (Ci-4 alkyl), SO₂(C₂.₄ alkynyl) , SO₂(C₂-₄ alkenyl) , OS(O)₂(Ci-₄ acyl), OS(O)₂(Ci-₄ rent),

OS(O)₂(C₂-₄ alkenyl), NH2, NH(Ci-₄ alkyl), NH(C₂.₄alkenyl), NH(C₂.₄ alkynyl), NH(Ci-₄ acyl), N(Ci-₄alkyl) 2, N(C_X-₄ acyl)₂;

(i) R¹⁰ and R¹¹ are independently H, F, Cl, Br, I, OH, OR', SH, SR', NH2, NHR' , NR'2, CxC6 lower alkyl, Cx-C6 halogenated lower alkyl (F, Cl, Br, I) Cx-C6 lower alkenyl, C2-C6 halogenated lower alkenyl (F, Cl, Br, I), C2-C6 lower alkynyl such as C=CH, halogenated lower alkynyl (F, Cl, Br, I) of C2C6, lower alkyl of Cx-Ce, lower alkyl (F, Cl, Br, I) of halogenated Cx.6, CO2H, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R' with the proviso that R¹⁰ be OH and R¹¹ not be NH2;

wherein R' is an optionally substituted alkyl, including, but not limited to, a C_X.₂₀ optionally substituted alkyl, a C_x-_xox optionally substituted alkyl, an optionally substituted lower alkyl; an optionally substituted cycloalkyl; an optionally substituted alkynyl of C₂-C_yes, an optionally substituted lower alkenyl of C₂-C₆, or optionally substituted acyl, which includes but is not limited to C(O) alkyl, C(O)(C_x.₂₀ alkyl), C(O) (C_x._x0alkyl), or C(O)(lower alkyl) or alternatively, in place of NR'₂, each R' comprises at least one C atom which is joined to form a heterocycle comprising at least two carbon atoms; and (j) Z is N or CR¹²; and

R¹² is H, halogen (including F, Cl, Br, I) , OH, OR' ,

62/967

SH, SR', NH₂, NHR' , NR' 2, NO₂, Ci-C lower alkyl₆, lower alkyl (F, Cl, Br, I) halogenated from Ci-C₆, C lower alkenyl₂-C₆, halogenated lower alkenyl (F, Cl, Br, I), C lower alkynyl₂-C₆, lower alkynyl (F, Cl, Br, I) halogenated from C₂-C_yes, Ci-C lower alkoxy₆, lower alkyl (F, Cl, Br, I) halogenated from Ci-₆, CO₂H, CO₂R* , CONH₂, CONHR' , CONR'₂, CH=CHCO₂H, or CH=CHCO₂R'.

The second aspect of the third modality is directed to the compound represented by formula 1-5:

where (a) R¹ is hydrogen, methyl, ethyl, n-propyl, ipropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b) R² is hydrogen or CH₃ ;

(c) R^3rd is H and R^3b 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, CH₂CH₂CH₂CH2NH_2zCH₂CH₂CH₂NHC(NH)NH₂, CH₂-imidazol-4-yl, CH₂OH, CH(OH)CH₃, CH₂ ( (4'-OH)-Ph), CH₂SH, or lower cycloalkyl;

(d) R⁴ is hydrogen, CH₃, And,^xYes,ⁿYes,ⁿBu, 2-butyl,^bBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, halolower alkyl or di(lower alkyl)amino-lower alkyl;

(e) R⁵ is H, CN, CH3, OCH3, CH2OH, CH2F, halogen, including F, Cl, Br or I, with the proviso that when X is OH, R⁶ is CH3 or CH₂F, R⁵ cannot be H;

(f) R⁶ is H, CH₃, CH₂F, CHF₂, CF_3rd F, OR CN;

63/967 (q) 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', with the condition that R¹⁰ is OH and R¹¹ it's not NH₂;

where R' is lower alkyl, lower cycloalkyl or C(O)(lower alkyl) or, alternatively, in the case of NR'₂, each R' ccomprises at least one C atom that is linked to form a heterocycle that comprises at least two carbon atoms; and (j) Z is N or CR¹²; and

R¹² is a H, halogen (including F, Cl, Br, I), OR', NH₂, NHR', NR'₂, NOz, d Ci-C lower alkyl₆, CO₂R', CONH₂, CONHR', CONR'₂, CH=CHCO₂H, or CH=CHCO₂R'.

The third aspect of the third modality is directed to the compound represented by formula 1-5:

where (a) R¹ is hydrogen, methyl, ethyl, n-propyl, ipropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b) R² is hydrogen or CH₃ ;

(c) R^3rd is H and R^3b is H, CH₃, CH(CH₃)₂, CH₂CH(CH₃)₂, CH (CH₃) CH₂CH₃, CH₂Ph, or lower cycloalkyl;

(d) R⁴ is hydrogen, CH₃, And,^xYes,ⁿYes,ⁿBu, 2-butyl,^cBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, di(alkyl

64/967 lower)amino-lower alkyl;

(e) R⁵ is H, CN, CH2F, F, Cl, Br, or I; with the condition that X is OH, R⁶ is CH3 or CH₂F, R⁵ it cannot be Η;

(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' , NR¹ 2, CO2R' , CONH2 , CONHR' , CONR' 2, CH=CHCO2H, or CH=CHCO2R', with the condition that R¹⁰ is OH and R¹¹ it is not NH2;

where R' is lower alkyl, lower cycloalkyl or C(O)(lower alkyl) or, alternatively, in the case of NR'₂, each R' ccomprises at least one C atom that is linked to form a heterocycle that comprises at least two carbon atoms; and (j ) Z is N or CR¹²; and

R¹² is a H, halogen (including F, Cl, Br, I), OR', NH₂, NHR', NR'₂, N0₂, lower alkyl of Ci~C₆, CO₂R', CONH₂ , CONHR', CONR'₂, CH=CHCO₂H, or CH=CHCO₂R ' .

The fourth aspect of the third modality is directed to the compound represented by formula 1-5:

where (a) R¹ is hydrogen, methyl, ethyl, n-propyl, ipropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b) R² is hydrogen;

(c) R^3rd is H and R^3b is H, CH₃, CH(CH₃)₂, CH₂CH(CH₃)₂, CH (CH₃) CH₂CH₃, CH₂Ph, or lower cycloalkyl, - (d) R⁴ is hydrogen, CH₃, And,^andYes,ⁿYes,ⁿBu, 2-butyl,

65/967 ^andBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methylpiperidin-4-yl, halolower alkyl, di(lower alkyl)amino-lower alkyl;

(e) R⁵ is H, with the condition that, when X is OH, R⁶is CH₃ or CH₂F, R⁵ it cannot be Η;

(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', with the condition that R¹⁰ is OH and R¹¹ it is not NH₂ ,· where R' is a lower alkyl, lower cycloalkyl or C(0)(lower alkyl) or, alternatively, in the case of NR'₂, each R' ccomprises at least one C atom that is linked to form a heterocycle that comprises at least two carbon atoms; and (j ) Z is N or CR¹²; and

R¹² is a H, halogen (including F, Cl, Br, I), OR', NH₂, NHR', NR'₂, N0₂, Ci-C lower alkyl₆, CO₂R', CONH₂, CONHR', CONR'₂, CH=CHCO₂H, or CH=CHCO₂R'.

The fifth aspect of the third modality is directed to the compound represented by formula 1-5:

where (a) R¹ is hydrogen, methyl, phenyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b) R² is hydrogen;

(C) R^3rd is H and R^3b is H, CH₃, CH(CH₃)₂, CH₂CH(CH₃)₂,

66/967

CH(CH₃) CH₂CH₃, CH₂Ph, or lower cycloalkyl;

(d) R⁴ is hydrogen, CH₃, And,^xYes,ⁿYes,ⁿBu, 2-butyl,^cBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methylpiperidin-4-yl, halolower alkyl, di(lower alkyl)amino-lower alkyl;

(e) R⁵ is H, with the condition that, when X is OH, R^andis CH₃ or CH₂F, R⁵ it cannot be Η;

(f) R⁵ 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', with the condition that R¹⁰ is OH and R¹¹ it is not NH₂ ;

where R' is lower alkyl, lower cycloalkyl or C(O)(lower alkyl) or, alternatively, in the case of NR¹₂, each R' ccomprises at least one C atom that is linked to form a heterocycle that comprises at least two carbon atoms; and (j) Z is N or CR¹²; and

R¹² is a H, halogen (including F, Cl, Br, I), OR', NH₂, NHR', NR'₂, NO₂, Ci-C lower alkyl_yes, CO₂R', CONH₂, CONHR', CONR'₂, CH=CHCO₂H, or CH=CHCO₂R'.

The sixth aspect of the third modality is directed to the compound represented by formula 1-5:

where (a) R¹ is hydrogen, methyl, ethyl, n-propyl, ipropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl,

67/967 p-fluorophenyl;

(b) R² is hydrogen or CH₃ ;

(c) R_3rd is H and R^3b 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;

(d) R⁴ is hydrogen, CH₃, And,^andYes,ⁿYes,ⁿBu, 2-butyl,^bBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methylpiperidin-4-yl, halolower alkyl, di(lower alkyl)amino-lower alkyl;

(e) R⁵ is H, CN, CH3, OCH3, CH2OH, CH2F, halogen, including F, Cl, Br or I, with the proviso that when X is OH, R⁶ is CH3 or CH₂F, 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, NH₂, N₃, CN, Cl, Br, F, I, OC(O)CH₃, OCH₃;

(i) R¹⁰ is NH2 and R¹¹ is H, F, Br, I, OH, OR', NH2, NHR',

NR'₂, CO₂R', CONH₂, CONHR', CONR'₂, CH=CHCO₂H, or CH=CHCO₂R'; where R' is lower alkyl, lower cycloalkyl or C(O)(lower alkyl) or, alternatively, in the case of NR'₂, each R' ccomprises at least one C atom that is linked to form a heterocycle that comprises at least two carbon atoms; and (j ) Z is N or CR¹²; and

R¹² is a H, halogen (including F, Cl, Br, I), OR', NH₂, NHR', NR'₂, NO₂, Ci-C lower alkyl_yes, CO₂R',

68/967

CONH₂, CONHR', CONR'₂, CH=CHCO₂H, or CH=CHCO₂R'.

The seventh aspect of the third modality is directed to the compound represented by formula 1-5:

where (a) R¹ is hydrogen, methyl, ethyl, n-propyl, ipropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p- fluorophenyl,· (b) R² is hydrogen or CH₃;

(c) R^3rd is H and R^3b is H, CH₃, CH(CH₃)₂, CH₂CH(CH₃)₂,

CH (CH₃) CH₂CH_3z CH₂Ph, or lower cycloalkyl;

(d) R⁴ is hydrogen, CH₃, And,^xYes,ⁿYes,ⁿBu, 2-butyl, 'Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methylpiperidin-4-yl, lower haloalkyl, di(lower alkyl)amino-lower alkyl;

(e) R⁵ is H, CN, CH2F, F, Cl, Br, or I; with the condition that X is OH, R⁶ is CH3 or CH₂F, R⁵ cannot be H;

(f) R⁶ is H, CH₃, CH₂F, CHF_2z 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 and R¹¹ is H, F, Br, I, OH, OR', NH2, NHR',

NR'₂, CO₂R', CONH₂, CONHR', CONR'_2z CH=CHCO₂H, or CH=CHCO₂R';

where R' is a lower alkyl, lower cycloalkyl or C (O) (lower alkyl) or, alternatively, in the case of NR'₂, each R' ccomprises at least one C atom that is linked to form a heterocycle that comprises at least two carbon atoms; and (j) Z is N or CR¹²; and

69/967

R¹² is a H, halogen (including F, Cl, Br, I), OR', NH₂, NHR', NR'₂, NO₂, lower alkyl of Cx-C₆, CO₂R', CONH₂, CONHR', CONR'_2z CH=CHCO₂H, or CH=CHCO₂R'.

The eighth aspect of the third modality is directed to the compound represented by formula 1-5:

where (a) R¹ is hydrogen, methyl, ethyl, n-propyl, ipropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b) R² is hydrogen;

(c) R^3rd is H and R^3b is H, CH₃, CH(CH₃)₂, CH₂CH(CH₃)₂, CH (CH₃) CH₂CH₃, CH₂Ph, or lower cycloalkyl;

(d) R⁴ is hydrogen, CH₃, And,^xYes,ⁿYes,ⁿBu, 2-butyl,^lBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methylpiperidin-4-yl, lower haloalkyl;

(e) R⁵ is H, with the condition that, when X is OH, R^andis CH₃ or CH₂F, 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 H, F, Br, I, OH, OR', NH2, NHR',

NR '₂ , CO₂R', CONH₂ , CONHR' , CONR '₂ , CH=CHCO₂H, or CH=CHCO₂R';

where R' is lower alkyl, lower cycloalkyl or C(O)(lower alkyl) or, alternatively, in the case of NR'₂, each R' ccomprises at least one C atom that is linked to form a heterocycle that comprises at least two carbon atoms; and (j) Z is N or CR¹²; and

70/967

R¹² is a H, halogen (including F, Cl, Br, I), OR', NH₂, NHR', NR'_2z NO₂, Ci-C lower alkyl₆, CO₂R', CONH₂, CONHR', CONR'₂, CH=CHCO₂H, or CH=CHCO₂R'.

The ninth aspect of the third modality is directed to the compound represented by formula 1-5:

where (a) R¹ is hydrogen, methyl, phenyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b) R² is hydrogen;

(c) R^3rd is H and R^3b is H, CH₃, CH(CH₃)₂, CH₂CH(CH₃)₂, CH(CH₃) CH₂CH₃, CH₂Ph, or lower cycloalkyl;

(d) R⁴ is hydrogen, CH₃, And,¹Yes,ⁿYes,ⁿBu, 2-butyl,^bBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, or N-methyl-pyrrolidin-4-yl, halolower alkyl or di(lower alkyl)amino-lower alkyl;

(e) R⁵ is H, with the condition that, when X is OH, R⁶is CH₃ or CH₂F, 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 H, F, Br, I, OH, OR', NH2, NHR',

NR'₂, CO₂R', CONH₂, CONHR', CONR'₂, CH=CHCO₂H, or CH=CHCO₂R';

where R' is lower alkyl, lower cycloalkyl or C(O)(lower alkyl) or, alternatively, in the case of NR*₂, each R' ccomprises at least one C atom that is linked to form a heterocycle that comprises at least two carbon atoms; and (j) Z is N or CR¹²; and

71/967 _ri2 -_{an H}, halogen (including F, Cl, Br, I), OR', NH₂, NHR', NR'₂, N0_2z Ci-C lower alkyl₆, C0₂R', CONH₂, CONHR', CONR'₂, CH=CHCO₂H, OR CH=CHCO₂R'.

The tenth aspect of the third modality is directed to the compound represented by formula 1-6:

R'°

<img file="BRPI0809654A2_D0010.tif" />

1-6 where (a) R¹ is hydrogen, n-alkyl; branched alkyl; cycloalkyl; or aryl, which includes, but is not limited to, phenyl or naphthyl, wherein phenyl or naphthyl is optionally substituted with at least one of Ci-6 alkyl, C2.6 alkenyl, C2_6 alkynyl, Ci-6 alkoxy, F, Cl, Br, I, nitro, cyano, Ci-6 haloalkyl, -N(R¹')2, Ci-₆ acylamino, -NHSO₂C_x-₆rent, -SO₂N(R¹')2, COLOR¹, and -SO2Ci-₆ rent; (R¹' is independently hydrogen or alkyl, which includes, but is not limited to, C1-20 alkyl, C1-10 alkyl, or C1-6 alkyl, R¹ is -OR' or -N(R¹')2);

(b) R² is hydrogen or CH₃;

(c) R^3rd and R^3b are (i) independently selected from hydrogen, Ci-ho alkyl, cycloalkyl, - (CH2) c (NR³') 2, Cx-6 hydroxyalkyl, -CH₂SH, - (CH₂) ₂Yes (O)_dMe, (CH₂)₃NHC(=NH)NH₂, (1H-indol-3-yl)methyl, (1H-imidazol-4yl)methyl, - (CH₂)eCOR³ ', aryl and aryl Cl-3 alkyl, said aryl groups optionally substituted by a group

72/967 selected from hydroxyl, Ci-io alkyl, Cl-6 alkoxy, halogen, nitro and cyano; (ii) R^3rd and R^3b both are Cx-6 alkyl; (iii) R^3rd and R^3b together they are (CH₂)f so as to form a spiro ring; (iv) R^3rd is hydrogen and R^3b and R² together they are (CH2)n so as to form a cyclic ring that includes the adjacent atoms N and C (v) R^3b is hydrogen and R^3rd and R²together they are (CH2)_n so as to form a cyclic ring that includes adjacent atoms N and C, where c is 1 to 6, déOa 2, eé0a3, f is 2 to 5, né2a4, and where R³' is independently hydrogen or Ci-₆ rent and R³ is -OR' or —N(R³ )2); (vi) R^3rd is H and R^3b 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) R^3rd 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 and R^3b is H, where R³' is independently hydrogen or alkyl, which includes, but is not limited to, Ci-20 alkyl, C_x-io alkyl, or Cl-6 alkyl, R³ is -OR' or -N(R³')₂);

(d) R⁴ is hydrogen, C!-₁₀ rent, Ci-₁₀ alkyl optionally substituted by a lower alkyl, alkoxy or halogen, Ci-₁₀ haloalkyl, C₃-i₀ cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aminoacyl, di(lower alkyl)amino-lower alkyl, aryl, such as phenyl, heteroaryl, such as, pyridinyl, substituted aryl, or substituted heteroaryl;

73/967 (e) R⁵ is H, a lower alkyl, CN, vinyl, O(lower alkyl), hydroxyl lower alkyl, that is, (CH₂)_pOH, where p is 1-6, including hydroxyl methyl (CH₂OH) , CH₂F, N₃, CH₂CN, CH₂NH₂, CH₂NHCH₃, CH₂N(CH₃)₂, alkyne (optionally substituted), or halogen, including F, Cl, Br, or I, with the proviso that when X is OH, base is cytosine and R⁶ is H, R⁵ it cannot be N3 and when X is OH, R⁶is CH3 or CH₂F and B is a purine base, R⁵ it cannot be Η;

(f) R^yes 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, Ci-4 alkyl, C₂.₄ alkenyl, C₂.₄alkynyl, vinyl, N₃, CN, Cl, Br, F, I, NO₂, OC(O)O(C!.₄alkyl), OC(O)O(Ci-₄ alkyl), OC(O)O(C₂_₄ alkynyl), OC(O)O(C₂.₄ alkenyl), 0Ci-i₀ haloalkyl, O (aminoacyl) , 15 0(Ci-io acyl) , 0(Ci-₄ rent), 0(C₂.₄ alkenyl), S(Ci-₄acyl) , S(Ci-₄ rent), S(C₂-₄ alkynyl), S(C₂_₄ alkenyl), SO(Ci-₄ acyl), SO(Ci-₄ alkyl), SO(C₂_₄ alkynyl), S0(C₂.₄alkenyl), SO₂(Ci-₄ acyl), SO₂ (C_x-₄ rent), SO₂(C₂_₄alkynyl), SO₂(C₂.₄ alkenyl), OS(O)₂(Ci-₄ acyl), 20 OS(O)₂(Ci-₄ rent), OS(O)₂(C₂_₄ alkenyl), NH₂, NH(Ci-₄ alkyl), NH(C₂.₄ alkenyl), NH(C₂-₄ alkynyl), NH(Ci-₄acyl), N(Ci-₄ rent)₂, N(C1-18 acyl)₂, in which alkyl, alkynyl, alkenyl and vinyl are optionally substituted by N₃, CN, one to three halogens (Cl, Br, F, 25 I), NO₂, C(O)O(Ci-₄ alkyl), C(O)O(Ci-₄ alkyl), C(O)O(C₂.₄ alkynyl), C(O)O(C₂.₄ alkenyl), O(Ci-₄ acyl), O(Ci-₄alkyl), O(C₂.₄ alkenyl), S(Ci-₄ acyl), S(C_X.₄ rent), S(C₂_₄ alkynyl), S(C₂.₄ alkenyl), SO(C_x-₄ acyl), SO(C_V4alkyl), SO(C₂.₄ alkynyl), SO(C₂.₄ alkenyl), SO₂ (Ci-₄30 acyl), SO₂(Ci-₄ rent), SO₂(C₂.₄ alkynyl), SO₂(C₂.₄

74/967 alkenyl), OS(O)₂(Ci_₄ acyl), OS(O)₂(Ci-₄ rent), OS(O)₂(C₂_₄ alkenyl), NH₂, NH(Ci-₄ alkyl), NH(C₂_₄alkenyl), NH(C₂_₄ alkynyl), NH(Ci-₄ acyl), N(Ci-₄rent)₂, N(Ci-₄ acyl)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', with the condition that R¹⁰ is OH and R¹¹ it is not NH₂;

where R' is a lower alkyl, lower cycloalkyl 10 or C(O)(lower alkyl) or, alternatively, in the case of NR'2, each R' ccomprises at least one C atom which is linked to form a heterocycle comprising at least two carbon atoms; and (j ) Z is N or CR¹²; and

R¹² is a H, halogen (including F, Cl, Br, I) , OR' ,

NH₂, NHR', NR'₂, NO₂, lower alkyl of C_x-C₆, CO₂R', CONH₂, CONHR', CONR'2, CH=CHCO₂H, or CH=CHCO₂R'.

The eleventh aspect of the third modality is directed to the compound represented by formula 1-6:

0 where (a) R¹ is hydrogen, methyl, ethyl, n-propyl, ipropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b) R² is hydrogen or CH₃;

(c) R^3rd is H and R^3b 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-irnidazol-4-yl, CH2OH, CH(OH)CH₃, CH₂ ( (4 '-OH)-Ph) , CH₂SH, or lower cycloalkyl;

(d) R⁴ is hydrogen, CH₃, And,^xYes,ⁿYes,ⁿBu, 2-butyl,

75/967 ^fcBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methylpiperidin-4-yl, halolower alkyl, di(lower alkyl)amino-lower alkyl;

(e) R⁵ is H, CN, CH3, OCH3, CH2OH, CH2F, halogen, including F, Cl, Br or I, with the proviso that when X is OH, R⁶ is CH3 or CH₂F, 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, 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', with the proviso that R¹⁰ is OH and R¹¹ it is not NH2;

where R' is lower alkyl, lower cycloalkyl or C(O) (lower alkyl) or, alternatively, in the case of NR'₂, each R' ccomprises at least one C atom that is linked to form a heterocycle that comprises at least two carbon atoms; and (j ) Z is N or CR¹²; and

R¹² is a H, halogen (including F, Cl, Br, I), OR', NH₂, NHR', NR'2, N0₂, Cx-Cg lower alkyl, CO₂R',

CONH₂, CONHR', CONR'₂, CH=CHCO₂H, or CH=CHCO₂R'.

The twelfth aspect of the third modality is directed to the compound represented by formula 1-6:

where (a) R¹ is hydrogen, methyl, ethyl, n-propyl, ipropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl,

76/967 p-fluorophenyl;

(b) R² is hydrogen or CH₃;

(c) R^3rd is H and R^3b is H, CH₃, CH(CH₃)₂, CH₂CH(CH₃)₂, CH (CH₃) CH₂CH₃, CH₂Ph, or lower cycloalkyl;

(d) R⁴ is hydrogen, CH₃, And,¹Yes,ⁿYes,ⁿBu, 2-butyl,^fcBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methylpiperidin-4-yl, halolower alkyl, di(lower alkyl)amino-lower alkyl;

(e) R⁵ is H, CN, CH2F, F, Cl, Br, or I; with the condition that X is OH, R⁶ is CH3 or CH₂F, R⁵ it cannot be Η;

(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'_2zCH=CHCO₂H, or CH=CHCO₂R', with the condition that R¹⁰ is OH and R¹¹ it is not NH₂;

where R' is lower alkyl, lower cycloalkyl or C(O)(lower alkyl) or, alternatively, in the case of NR'₂, each R' ccomprises at least one C atom that is linked to form a heterocycle that comprises at least two carbon atoms; and (j) Z is N or CR¹²; and

R¹² is a H, halogen (including F, Cl, Br, I), OR', NH₂, NHR', NR'₂, NO₂, Ci-C lower alkyl₆, CO₂R', CONH₂, CONHR', CONR'₂, CH=CHCO₂H, or CH=CHCO₂R'.

thirteenth aspect of the third modality is

77/967 directed to the compound represented by formula 1-6: where (a) R¹ is hydrogen, methyl, ethyl, n-propyl, ipropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b) R² is hydrogen;

(c) R^3rd is H and R^3b is H, CH₃, CH(CH₃)₂, CH₂CH(CH₃)₂, CH (CH₃) CH₂CH₃, CH₂Ph, or lower cycloalkyl;

(d) R⁴ is hydrogen, CH₃, And,¹Yes,ⁿYes,ⁿBu, 2-butyl,^cBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methylpiperidin-4-yl, halolower alkyl, di(lower alkyl)amino-lower alkyl;

(e) R⁵ is H, with the condition that, when X is OH, R^yesis CH₃ or CH₂F, R^yes 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 , CO₂R¹ , CONH2 , CONHR' , CONR' 2, CH=CHCO2H, or CH=CHCO2R', with the condition that R¹⁰ is OH and R¹¹ it is not NH2;

where R' is lower alkyl, lower cycloalkyl or C(O)(lower alkyl) or, alternatively, in the case of NR'₂, each R' ccomprises at least one C atom that is linked to form a heterocycle that comprises at least two carbon atoms; and (j ) Z is N or CR¹²; and

R¹² is a H, halogen (including F, Cl, Br, I), OR',

78/967

NH₂, NHRA¹ , NR' 2, NO₂, lower alkyl of Ci~C₆, CO₂R', CONH₂, CONHR', CONR'₂, CH=CHCO₂H, or CH=CHCO₂R'.

The fourteenth aspect of the third modality is directed to the compound represented by formula 1-6:

where (a) R¹ is hydrogen, methyl, phenyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b) R² is hydrogen;

(c) R^3rd is H and R^3b is H, CH₃, CH(CH₃)₂, CH₂CH(CH₃)₂, CH (CH₃) CH₂CH₃, CH₂Ph, or lower cycloalkyl;

(d) R⁴ is hydrogen, CH₃, And,^toYes,ⁿYes,ⁿBu, 2-butyl,^fcBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methylpiperidin-4-yl, halolower alkyl, di(lower alkyl)amino-lower alkyl;

(e) R⁵ is H, with the condition that, when X is OH, R⁶is CH₃ or CH₂F, 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', with the condition that R¹⁰ is OH and 11 ~

R is not NH₂;

where R' is a lower alkyl, lower cycloalkyl or C(O)(lower alkyl) or, alternatively, in the case of NR'2, each R' ccomprises at least one C atom which is linked to form a heterocycle comprising at least two carbon atoms, - and

79/967 (j) Z is N or CR¹²; and

R¹² is a H, halogen (including F, Cl, Br, I), OR', NH₂, NHR', NR'2, NO₂, Ci-C lower alkyl₆, CO₂R', CONH₂ , CONHR', CONR'₂, CH=CHCO₂H, or CH=CHCO₂R'.

The fifteenth aspect of the third modality is directed to the compound represented by formula 1-6: where (a) R¹ is hydrogen, n-alkyl; branched alkyl; cycloalkyl; or aryl, which includes, but is not limited to, phenyl or naphthyl, wherein phenyl or naphthyl is optionally substituted with at least one of Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 alkoxy, F, Cl, Br, I, nitro, cyano, Ci-6 haloalkyl, -N(R¹')2, Ci-_and acylamino, -NHSO₂Ci-₆rent, -SO₂N(R¹')2, COLOR¹, and -SO2Ci-₆ rent; (R¹' is independently hydrogen or alkyl, which includes, but is not limited to, Ci-20 alkyl, Ci-10 alkyl, or Ci-6 alkyl, R¹ is -OR' or -N(R¹’)2);

(b) R² is hydrogen or CH₃;

(c) R^3rd and R^3b are (i) independently selected from hydrogen, Ci-10 alkyl, cycloalkyl, - (CH2) c (NR³') 2, Ci-6 hydroxyalkyl, -CH₂SH, - (CH₂) ₂S(O)dMe, (CH₂)₃NHC(=NH)NH₂, (1H-indol-3-yl)methyl, (1H-imidazol-4yljmethyl, - (CH₂) eCOR³, aryl and aryl C_x-₃ alkyl, said aryl groups optionally substituted by a group selected from hydroxyl, C 1-6 alkyl, C 1-6 alkyl, halogen, nitro and cyano; (ii) R^3rd and R^3b both are C 1-6 alkyl; (iii) R^3rd and R^3b together they are (CH2)_f so as to form a spiral ring; (iv) R^3rd is hydrogen and R^3b and R² together they are (CH₂)n so as to form a cyclic ring that includes the adjacent atoms N and C (v) R^3b is hydrogen and R^3rd and R²

80/967 together are (CH₂)_n so as to form a cyclic ring that includes adjacent atoms N and C, where c is 1 to 6, déOa 2, eé0a3, f is 2 to 5, né2a4, and where R³' is independently hydrogen or Ci-6 alkyl and R³ is -OR' N(R³')2); (vi) R^3rd is H and R^3b 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) R^3rd is CH3, -CH₂CH₃, CH(CH₃)₂, CH₂CH(CH₃)₂, CH(CH₃) CH₂CH_3z 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)CH_3zCH₂ ( (4 '-OH)-Ph) , CH₂SH, or lower cycloalkyl and R^3b is H, where R³' is independently hydrogen or alkyl, which includes, but is not limited to, C1-20 alkyl, C1-10 alkyl, or C1-6 alkyl, R³ is -OR' or -N(R³')2);

(d) R⁴ is hydrogen, C_x-₁₀ rent, C_x-io alkyl optionally substituted by a lower alkyl, alkoxy or halogen, Ci-i₀ haloalkyl, C₃.₁₀ cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aminoacyl, di(lower alkyl)amino-lower alkyl, aryl, such as phenyl, heteroaryl, such as, pyridinyl, substituted aryl, or substituted heteroaryl;

(e) R⁵ is H, a lower alkyl, CN, vinyl, O(lower alkyl), hydroxyl lower alkyl, that is, (CH₂)_POH, where p is 1-6, including hydroxyl methyl (CH₂OH) , CH₂F, N_3z CH₂CN, CH₂NH₂, CH₂NHCH₃, CH₂N(CH₃)₂, alkyne (optionally substituted), or halogen, including F, Cl, Br, or I, with the proviso that when X is OH, the base is

81/967 cytosine and R⁶ is H, R⁵ it cannot be N3 and when X is OH, R⁶is CH3 or CH₂F and B is a purine base, R⁵ cannot be H;

(f) R^and 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, Ci-4 alkyl, C₂.₄ alkenyl, C₂.₄alkynyl, vinyl, N₃, CN, Cl, Br, F, I, NO₂, OC(O)O(Ci-₄alkyl), OC(O)O(Ci-₄ alkyl), OC(O)O(C₂-₄ alkynyl), OC(O)O(C₂.₄ alkenyl), OCi-io haloalkyl, O (aminoacyl) , ©(Cx-io acyl) , O(Ci-₄ alkyl), O(C₂_₄ alkenyl), S(Ci-₄acyl) , S(Ci-₄ rent), S(C₂.₄ alkynyl), S(C₂.₄ alkenyl), SO(Ci-₄ acyl), SO(Ci-₄ alkyl), SO(C₂.₄ alkynyl), SO(C₂.₄alkenyl), SO₂(Ci-₄ acyl), SO₂(Ci-₄ rent), SO₂(C₂.₄alkynyl), SO₂(C₂_₄ alkenyl), OS(O)₂(Ci-₄ acyl), 03(0)2(0^ alkyl), OS(O)₂(C₂-₄ alkenyl), NH₂, NH(C_x-₄alkyl), NH(C₂.₄ alkenyl), NH(C₂-₄ alkynyl), NH(Ci-₄acyl), N(Ci-₄ rent)₂, N(C1-18 acyl)₂, in which alkyl, alkynyl, alkenyl and vinyl are optionally substituted by N₃, CN, one to three halogens (Cl, Br, F, I) , NO₂, C(O)O(Ci-₄ alkyl), C(O)O(Ci-₄ alkyl), C(O)O(C₂.₄alkynyl), C(O)O(C₂.₄ alkenyl), O(Ci-₄ acyl), O(Ci-₄alkyl), O(C₂_₄ alkenyl), S(Ci-₄ acyl), S(Ci-₄ rent), S(C₂.₄ alkynyl), S(C₂_₄ alkenyl), SO(Ci-₄ acyl), SO(Ci-₄alkyl), SO(C₂.₄ alkynyl), SO(C₂-₄ alkenyl), SO2 (C_x-₄acyl), SO₂(Ci-₄ rent), SO₂(C₂_₄ alkynyl), SO₂(C₂_₄alkenyl), OS(O)₂(C_X.₄ acyl), OS(O)₂(C_X.₄ rent), OS(O)₂(C₂_₄ alkenyl), NH₂, NH(C_x-₄ alkyl), NH(C₂_₄alkenyl) , NH(C₂.₄ alkynyl), NH(C_X.₄ acyl), N(C_x.₄ rent) 2/ N(C_X.₄ acyl)₂;

(i) R¹⁰ is NH2 and R¹¹ is H, F, Br, I, OH, OR¹, NH₂, NHR' ,

NR'₂, CO₂R' , CONH2, CONHR', CONR'₂, CH=CHCO₂H, or CH=CHCO₂R¹ ;

82/967 where R' is a lower alkyl, lower cycloalkyl or C(O) (lower alkyl) or, alternatively, in the case of NR'2, each R' ccomprises at least one C atom which is linked to form a heterocycle comprising at least two carbon atoms; and (j) Z is N or CR¹²; and

R¹² is a H, halogen (including F, Cl, Br, I), OR', NH₂, NHR', NR'₂, N0₂, lower alkyl of 0χ-0₆, CO₂R', CONH₂, CONHR', CONR'₂, CH=CHCO₂H, or CH=CHCO₂R'.

sixteenth aspect of the third modality is directed to the compound represented by formula 1-6:

where (a) R¹ is hydrogen, methyl, ethyl, n-propyl, ipropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b) R² is hydrogen or CH₃ ;

(c) R^3rd is H and R^3b 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;

(d) R⁴ is hydrogen, CH₃, And,^xYes,ⁿYes,ⁿBu, 2-butyl,^bBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methylpiperidin-4-yl, halolower alkyl, di(lower alkyl)amino-lower alkyl;

(e) R⁵ is H, CN, CH3, OCH3, CH2OH, CH2F, halogen, including F, Cl, Br or I, with the proviso that when X is OH, R^yes is CH3 or CH₂F, R⁵ cannot be H;

83/967 (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 and R¹¹ is H, F, Br, I, OH, OR', NH2, NHR',

NR '₂, CO₂R', CONH₂, CONHR', CONR'₂, CH=CHCO₂H, or CH=CHCO₂R';

where R' is lower alkyl, lower cycloalkyl or C(O) (lower alkyl) or, alternatively, in the case of NR'_2z each R' ccomprises at least one C atom that is linked to form a heterocycle that comprises, at least, two carbon atoms; and (j) Z is N or CR¹²; and

R¹² is a H, halogen (including F, Cl, Br, I), OR', NH₂, NHR' , NR'₂, NO₂, Ci-C lower alkyl₆, CO₂R',

CONH₂, CONHR', CONR'₂, CH=CHCO₂H, or CH=CHCO₂R'.

A seventeenth aspect of the third modality is directed to a compound represented by formula 1-6: where (a) R¹ is hydrogen, methyl, ethyl, n-propyl, ipropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b) R² is hydrogen or CH₃;

(c) R^3rd is H and R^3b is H, CH₃, CH(CH₃)₂, CH₂CH(CH₃)₂, CH (CH₃) CH₂CH₃ , CH₂Ph, or lower cycloalkyl;

(d) R⁴ is hydrogen, CH₃, And,^xYes,ⁿYes,ⁿBu, 2-butyl, *Έη, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methylpiperidin-4-yl, lower haloalkyl, di(lower alkyl)amino-lower alkyl;

84/967 (e) R⁵ is H, CN, CH2F, F, Cl, Br, or I; with the condition that X is OH, R⁶ is CH3 or CH₂F, R⁵ it cannot be Η;

(f) R^yes 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 and R¹¹ is H, F, Br, I, OH, OR', NH2,

NHR ' , NR '₂ , CO₂R ' , CONH₂, CONHR ' , CONR '₂, CH=CHCO₂Oh, or

CH=CHCO₂R';

where R' is lower alkyl, lower cycloalkyl or C(O) (lower alkyl) or, alternatively, in the case of NR¹₂, each R' ccomprises at least one C atom that is linked to form a heterocycle that comprises at least two carbon atoms; and (j ) Z is N or CR¹²; and

R¹² is a H, halogen (including F, Cl, Br, I), OR', NH₂, NHR', NR'₂, N0_2z lower C-alkali_x-C₆, CO₂R', CONH₂, CONHR', CONR'₂, CH = CHCO₂H, or CH=CHCO₂R'.

The eighteenth aspect of the third modality is directed to the compound represented by formula 1-6:

where (a) R¹ is hydrogen, methyl, ethyl, n-propyl, ipropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chlorophenyl, p-fluorophenyl;

(b) R² is hydrogen;

(C) R^3rd is H and R^3b is H, CH₃, CH(CH₃)₂, CH₂CH(CH₃)₂,

CH (CH₃) CH₂CH₃, CH₂Ph, or lower cycloalkyl;

(d) R⁴ is hydrogen, CH₃, And,^TheYes,ⁿYes,ⁿBoo, 2

85/967 butyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, Nmethyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methylpyrrolidin-4-yl, N-methyl-piperidin-4-yl, halolower alkyl, di(lower alkyl)amino-lower alkyl;

(e) R⁵ is H, with the condition that, when X is OH, R⁶ is CH₃ or CH₂F, R⁵ it cannot be Η;

(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 H, F, Br, I, OH, OR', NH2, NHR', NR'₂, CO₂R', CONH₂, CONHR', CONR'₂, CH=CHCO₂H, or CH = CHCO₂R ' ;

where R' is lower alkyl, lower cycloalkyl or C(O) (lower alkyl) or, alternatively, in the case of NR'₂, each R' ccomprises at least one C atom that is linked to form a heterocycle that comprises, at least, two carbon atoms; and (j) Z is N or CR¹²; and

R12 is H, halogen (including F, Cl, Br, I), OR', NH₂, NHR', NR'₂, NO₂, lower alkyl of CO₂R', CONH₂, CONHR', CONR'₂, CH=CHCO₂H, or CH=CHCO₂R'.

The nineteenth aspect of the third modality is directed to the compound represented by formula 1-6: where (a) R¹ is hydrogen, methyl, phenyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b) R² is hydrogen;

(c) R^3rd is H and R^3b is H, CH₃, CH(CH₃)₂, CH₂CH(CH₃)₂,

86/967

CH(CH₃)CH₂CH₃, CH₂Ph, or lower cycloalkyl;

(d) R⁴ is hydrogen, CH₃, And,¹Yes,ⁿYes,ⁿBu, 2-butyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methylpiperidin-4-yl, halolower alkyl, di(lower alkyl)amino-lower alkyl;

(e) R⁵ is H, with the condition that, when X is OH, R⁶is CH₃ or CH₂F, R⁵ it cannot be Η;

(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 H, F, Br, I, OH, OR', NH2, NHR',

NR'₂, CO₂R', CONH₂, CONHR', CONR'₂, CH=CHCO₂H, OR CH=CHCO₂R'; where R' is lower alkyl, lower cycloalkyl or C(O)(lower alkyl) or, alternatively, in the case of NR'₂, each R' ccomprises at least one C atom that is linked to form a heterocycle that comprises at least two carbon atoms; and (j ) Z is N or CR¹²; and

R¹² is a H, halogen (including F, Cl, Br, I), OR', NH₂, NHR', NR'₂, N0₂, lower alkyl of Cx-C₆, CO₂R', CONH₂, CONHR', CONR'2, CH=CHCO₂H, or CH=CHCO₂R'.

A fourth embodiment of the invention is directed to the compound represented by formula I in which the base is a structure represented by formula c above, where R¹¹ is H and R², R^3rd, R^3b, R⁴, R⁵, R⁶, X and Y are defined in the Summary of the Invention section above.

The first aspect of the fourth modality is directed to the compound represented by formula 1-7:

87/967

<img file="BRPI0809654A2_D0011.tif" />

1-7 where (a) R¹ is hydrogen, n-alkyl; branched alkyl; cycloalkyl; or aryl, which includes, but is not limited to, phenyl or naphthyl, where phenyl or naphthyl is optionally substituted with at least one of Cx-6 alkyl, C2-6 alkenyl, C2.6 alkynyl, Cx-6 alkoxy, F, Cl, Br, I, nitro, cyano, Ci-6 haloalkyl, -N(R¹')2, C_x-e acylamino, -NHSO₂Ci-₆rent, -SO₂N(R¹')2, COLOR¹, and -SO2Ci-₆ rent; (R¹' is independently hydrogen or alkyl, which includes, but is not limited to, C1-20 alkyl, C1-10 alkyl, or C1-6 alkyl, R¹ is -OR' or -N(R¹')2);

(b) R² is hydrogen or CH₃;

(c) R^3rd and R^3b are (i) independently selected from hydrogen, Ci-io alkyl, cycloalkyl, - (CH2) c (NR³') 2, Ci-6 hydroxyalkyl, -CH₂SH, - (CH₂) ₂S (0) dMe, (CH₂)₃NHC(=NH)NH₂, (1H-indol-3-yl)methyl, (1H-imidazol-4yl)methyl, - (CH₂) eCOR³, aryl and aryl Ci-3 alkyl, said aryl groups optionally substituted by a group selected from hydroxyl, Ci-10 alkyl, Cl-6 alkoxy, halogen, nitro and cyano; (ii) R^3rd and R^3b both are Ci_6 alkyl; (iii) R^3rd and R^3b together they are (CH₂)_f so as to form a spiral ring, - (iv) R^3rd is hydrogen and R^3b and R² together they are

88/967 (CH₂)_n so as to form a cyclic ring that includes the adjacent atoms N and C (v) R^3b is hydrogen and R^3rd and R²together are (CH2)n so as to form a cyclic ring that includes adjacent atoms N and C, where cela6, déOa 2, eé0a3, f is 2 to 5, né2a4, and where R3¹ is independently hydrogen or Cr.₆ rent and R³ is -OR' or —N(R³')2); (vi) R^3rd is H and R^3b is H, CH3, CH₂CH₃, CH(CH₃)₂, CH₂CH(CH₃)₂, CH(CH₃) CH₂CH₃, CH₂Ph, CH₂-indol-3-yl, ch₂ch₂school₃, ch₂with₂h, CH₂C(O)NH_2z CH₂CH₂COOH, CH₂CH₂C(O)NH_2zCH₂CH₂CH₂CH₂NH₂, -CH₂CH₂CH₂NHC(NH)NH_2z CH₂-imidazol-4-yl, CH₂OH, CH(OH)CH_3z CH₂ ((4'-OH)-Ph) , CH₂SH, or lower cycloalkyl; or (viii) R^3rd is CH3, -CH2CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3) CH2CH3z CH2Ph, CH2-indol-3-Íl, -CH2CH2SCH3z 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 and R^3b is H, where R³' is independently hydrogen or alkyl, which includes, but is not limited to, Ci-20 alkyl, Ci-1o alkyl, or Ci-6 alkyl, R³ is -OR' or -N(R³')₂);

(d) R⁴ is hydrogen, Ci-i₀ alkyl, Ci-io alkyl optionally substituted by a lower alkyl, alkoxy or halogen, Ci-i₀ haloalkyl, C₃-i₀ cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aminoacyl, di(lower alkyl)amino-lower alkyl, aryl, such as phenyl, heteroaryl, such as, pyridinyl, substituted aryl, or substituted heteroaryl;

(e) R⁵ is H, a lower alkyl, CN, vinyl, O(lower alkyl), hydroxyl lower alkyl, that is, (CH₂)_pOH, where p is 1-6, including hydroxyl methyl (CH₂OH) , CH₂F, N₃, CH₂CN, CH₂NH₂, CH₂NHCH₃, CH₂N(CH₃)₂, alkyne

89/967 (optionally substituted), or halogen, including F, Cl, Br, or I, with the proviso that when X is OH, base is cytosine and R^yes is H, R⁵ it cannot be N3 and when X is OH, R⁶is CH3 or CH₂F and 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, Ci-4 alkyl, C₂_₄ alkenyl, C₂_₄alkynyl, vinyl, N₃, CN, Cl, Br, F, I, N0₂, OC(O)O(C_X_₄alkyl), OC(O)O(C_X-₄ alkyl), OC(O)O(C₂.₄ alkynyl), OC(O)O(C₂.₄ alkenyl), OCi-io haloalkyl, 0 (aminoacyl), 0(Ci-io acyl), O(C₁.₄ alkyl), O(C₂_₄ alkenyl), S(Ci-₄acyl), S(Ci-₄ rent), S(C₂-₄ alkynyl), S(C₂-₄ alkenyl), SO(Ci-₄ acyl), SO(C_X-₄ alkyl), SO(C₂_₄ alkynyl), SO(C₂_₄alkenyl), SO₂ (Ci-₄ acyl), SO₂(Ci-₄ rent), SO₂(C₂.₄alkynyl), SO2 (C₂.₄ alkenyl), OS(O)₂(Ci-₄ acyl), OS(O)₂(Ci-₄ rent), OS(O)₂(C₂_₄ alkenyl), NH₂, NH(Ci-₄alkyl), NH(C₂.₄ alkenyl), NH(C₂.₄ alkynyl), NH(Ci-₄acyl), N(C_x-4 rent)₂, N(C1-18 acyl)₂, in which alkyl, alkynyl, alkenyl and vinyl are optionally substituted by N₃, CN, one to three halogens (Cl, Br, F, I) , NO₂, C(O)O(C!-₄ alkyl), C(O)O(Ci-₄ alkyl), C(O)O(C₂_₄alkynyl), C(O)O(C₂.₄ alkenyl), O(Ci-₄ acyl), O(Ci-₄alkyl), O(C₂-₄ alkenyl), S(Ci-₄ acyl), S(C_x-₄ rent), S(C₂-₄ alkynyl), S(C₂-₄ alkenyl), SO(Ci-₄ acyl), SO(Ci-₄alkyl), SO(C₂.₄ alkynyl), SO(C₂-₄ alkenyl), SO₂(Ci-₄acyl), SO₂(Ci-₄ rent), SO₂(C₂-₄ alkynyl), SO₂(C₂.₄alkenyl), OS(O)₂(C₁.₄ acyl), OS(O)₂(C_X.₄ rent), OS(O)₂(C₂.₄ alkenyl), NH₂, NRÍC^ alkyl), NH(C₂.₄alkenyl), NH(C₂.₄ alkynyl), NH(Cx.₄ acyl), N(Οχ-₄ rent)₂, N(Ci-₄ acyl)₂;

90/967 (i) R¹⁰ is H, F, Cl, Br, I, OH, OR', SH, SR', NH₂,

NHR', NR¹2, Ci-C lower alkyl₆, lower alkyl (F, Cl, Br, I) halogenated from Ci-C₆, C lower alkenyl₂-C₆, lower alkenyl (F, Cl, Br, I) halogenated from C₂-C₆, C lower alkenyl₂-C₆ such as C^CH, C halogenated lower alkynyl (F, Cl, Br, I).₂-C_yes, Ci-C lower alkoxy₆, Ci-C halogenated lower alkyl (F, Cl, Br, I).₆, CO₂H, CO₂R', CONH₂, CONHR', CONR'₂, CH=CHCO₂H, or CH=CHCO₂R' , wherein R' is an optionally substituted alkyl, which includes, but is not limited to, a Ci-₂₀ optionally substituted alkyl, an optionally substituted C 1-1 alkyl, an optionally substituted lower alkyl; an optionally substituted cycloalkyl; an optionally substituted alkynyl of C₂-C₆, an optionally substituted lower alkenyl of C₂-C₆, or optionally substituted acyl, which includes but is not limited to C(O) alkyl, C(O) (Ci-₂₀ alkyl), C(O) (Ci-i₀alkyl), or C(O)(lower alkyl) or alternatively, in place of NR'₂, each R' comprises at least one C atom which is joined to form a heterocycle comprising at least two carbon atoms; and (j) Z is N or CR¹²; and

R¹² is H, halogen (including F, Cl, Br, I) , OH, OR' , SH, SR', NH₂, NHR', NR'₂, NO₂, Ci-C lower alkyl₆, lower alkyl (F, Cl, Br, I) halogenated from Ci-C₆, C lower alkenyl₂-C₆, halogenated lower alkenyl (F, Cl, Br, I), C lower alkynyl₂-C₆, lower alkynyl (F, Cl, Br, I) halogenated from C₂-C₆, Ci-C lower alkoxy₆, lower alkyl (F, Cl, Br, I)

91/967 Ci-C halogenated₆, CO₂H, CO₂R', CONH₂, CONHR', CONR'₂, CH=CHCO₂H, or CH=CHCO₂R'; with the condition that R¹² not be: (i) —C=CH, (ii) —C=CH₂, or (iii) -NO₂.

The second aspect of the fourth modality is directed to the compound represented by formula 1-7:

where (a) R¹ is hydrogen, methyl, ethyl, n-propyl, ipropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b) R² is hydrogen or CH₃ ;

(c) R^3rd is H and R^3b 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 ((4¹-OH)-Ph), CH2SH, or lower cycloalkyl;

(d) R⁴ is hydrogen, CH₃, And,^xYes,ⁿYes,ⁿBu, 2-butyl,^andBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methylpiperidin-4-yl, halolower alkyl, di(lower alkyl)amino-lower alkyl;

(e) R⁵ is H, CN, CH3, OCH3, CH2OH, CH2F, halogen, including F, Cl, Br or I, with the proviso that when X is OH, R⁶ is CH3 or CH₂F, R⁵ cannot be H;

(f) R^yes 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';

92/967 where R' is a lower alkyl, lower cycloalkyl or C(O)(lower alkyl) or, alternatively, in the case of NR'2, each R' ccomprises at least one C atom which is linked to form a heterocycle comprising at least two carbon atoms; and (j ) Z is N or CR¹²; and

R¹² is a H, halogen (including F, Cl, Br, I) , OR' , NH2, NHR' , NR¹2, NO2, Ci-C lower alkyl₆, CO₂R', CONH₂, CONHR', CONR'_2nd CH=CHCO₂H, or CH=CHCO₂R'; with the condition that R¹² is not one: (i) -C^CH, (ii) -C=CH₂, or (iii) -NO₂.

The third aspect of the third modality is directed to the compound represented by formula 1-7:

where (a) R¹ is hydrogen, methyl, ethyl, n-propyl, ipropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b) R² is hydrogen or CH₃;

(c) R^3rd is H and R^3b ê H, CH₃, CH(CH₃)₂, CH₂CH(CH₃)₂, CH (CH₃) CH₂CH₃, CH₂Ph, or lower cycloalkyl;

(d) R⁴ is hydrogen, CH₃, And,^xYes,ⁿYes,ⁿBu, 2-butyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methylpiperidin-4-yl, halolower alkyl, di(lower alkyl)amino-lower alkyl;

(e) R⁵ is H, CN, CH2F, F, Cl, Br, or I; with the condition that X is OH, R⁶ is CH3 or CH₂F, R⁵ cannot be H;

(f) R⁶ is H, CH₃, CH₂F, CHF₂, CF₃ or F;

(g) X is H, OH, F, OCH₃, F, Cl, Br, I, NH₂ or N₃;

93/967 (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, NHR¹, NR'2,

CO₂R', CONH₂, CONHR', CONR'_2/ CH=CHCO₂H, or CH=CHCO₂R';

where R' is lower alkyl, lower cycloalkyl or C(O)(lower alkyl) or, alternatively, in the case of NR¹₂, each R' ccomprises at least one C atom that is linked to form a heterocycle that comprises at least two carbon atoms; and (j ) Z is N or CR¹²; and

R¹² is a H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR' 2, NO2, Ci~Ce lower alkyl, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R'; with the condition that R¹² is not one: (i) -C=CH, (ii) -C=CH2, or (iii) -NO₂The fourth aspect of the fourth modality is directed to the compound represented by formula 1-7:

where (a) R¹ is hydrogen, methyl, ethyl, n-propyl, ipropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b) R² is hydrogen;

(c) R^3rd is H and R^3b is H, CH₃, CH(CH₃)₂, CH₂CH(CH₃)₂, CH (CH₃) CH₂CH₃, CH₂Ph, or lower cycloalkyl;

(d) R⁴ is hydrogen, CH₃, And,^xYes,ⁿYes,ⁿBu, 2-butyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methylpiperidin-4-yl, halolower alkyl, di(lower alkyl)amino-lower alkyl;

94/967 (e) R⁵ is H, with the condition that, when X is OH, R⁶is CH₃ or CH₂F, 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 H, F, Br, I, OH, OR', NH₂, NHR', NR'₂,

CO₂R', CONH₂, CONHR', CONR'_2nd CH=CHCO₂H, or CH=CHCO₂R';

where R' is lower alkyl, lower cycloalkyl or C(O)(lower alkyl) or, alternatively, in the case of NR'₂, each R' ccomprises at least one C atom that is linked to form a heterocycle that comprises at least two carbon atoms; and (j ) Z is N OR CR¹²; and

R¹² is a H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, Cx-C6 lower alkyl, CO2R', CONH2, CONHR', CONR'2z CH=CHCO2H, or CH=CHCO2R'; with the condition that R¹² is not one: (i) -C=CH, (ii) -C=CH2, or (iii) -NO₂.

The fifth aspect of the fourth modality is directed to the compound represented by formula 1-7:

where (a) R¹ is hydrogen, methyl, phenyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b) R² is hydrogen;

(c) R^3rd is H and R^3b is H, CH₃, CH(CH₃)₂, CH₂CH(CH₃)₂, CH (CH₃) CH₂CH₃, CH₂Ph, or lower cycloalkyl;

(d) R⁴ is hydrogen, CH₃, And,^toYes,ⁿYes,ⁿBu, 2-butyl,^cBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl

95/967 Piperidin-4-yl, halolower alkyl, di(lower alkyl)amino-lower alkyl;

(e) R⁵ is H, with the condition that, when X is OH, R⁶is CH₃ or CH₂F, R⁵ it cannot be Η;

(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';

where R' is lower alkyl, lower cycloalkyl or C(O)(lower alkyl) or, alternatively, in the case of NR'₂, each R' ccomprises at least one C atom that is linked to form a heterocycle that comprises at least two carbon atoms; and (j ) Z ê N or CR¹²; and

R¹² is a H, halogen (including F, Cl, Br, I), OR', NH₂, NHR', NR'₂, NO₂, Ci-C lower alkyl₆, CO₂R', CONH₂, CONHR', CONR'₂, CH=CHCO₂H, or CH=CHCO₂R'.

The sixth aspect of the fourth modality is directed to the compound represented by formula 1-8:

<img file="BRPI0809654A2_D0012.tif" />

1-8 where (a) R¹ is hydrogen, n-alkyl; branched alkyl,

96/967 cycloalkyl; or aryl, which includes, but is not limited to, phenyl or naphthyl, wherein phenyl or naphthyl is optionally substituted with at least one of Ci-₆ rent, C₂.₆alkenyl, C₂.₆ alkynyl, Ci-₆ alkoxy, F, Cl, Br, I, nitro, cyano, Ci-6 haloalkyl, -NIR¹ )₂, Ci-₆ acylamino, -NHSO₂Ci-₆rent, -SO₂N(R¹')2, COLOR¹, and -SO2Ci-₆ rent; (R¹' is independently hydrogen or alkyl, which includes, but is not limited to, Ci-₂₀ alkyl, Ci-io alkyl, or Ci-₆rent, R¹ is -OR' or -N(R¹')₂);

(b) R² is hydrogen or CH₃;

(c) R^3rd and R^3b are (i) independently selected from hydrogen, Ci-10 alkyl, cycloalkyl, - (CH2) c (NR³') 2, Ci-6 hydroxyalkyl, -CH₂SH, - (CH₂) ₂S(O)dMe, (CH₂) ₃NHC(=NH)NH₂, (1H-indol-3-yl)methyl, (1H-imidazol-4yl)methyl, - (CH₂) _andCOLOR³, aryl and aryl C_x.₃ alkyl, said aryl groups optionally substituted by a group selected from hydroxyl, Ci-io alkyl, Ci-₆ alkoxy, halogen, nitro and cyano; (ii) R^3rd and R^3b both are Cx-6 alkyl; (iii) R^3rd and R^3b together they are (CH2)f so as to form a spiro ring; (iv) R^3rd is hydrogen and R^3b and R² together are (CH2) n so as to form a cyclic ring that includes the adjacent atoms N and C (v) R^3b is hydrogen and R^3rd and R² together they are (CH₂)_n so as to form a cyclic ring that includes adjacent atoms N and C, where c is 1 to 6, déOa

2, eé0a3, f is 2 to 5, né2a4, and where R³ ' is independently hydrogen or Ci-6 alkyl and R³ is -OR' or —N(R³)2); (vi) R^3rd is H and R^3b 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,

97/967

CH₂OH, CH(OH)CH₃, CH₂ ((4¹-OH)-Ph), CH2SH, or lower cycloalkyl; or (viii) R^3rd 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 and R^3b is H, where R³' is independently hydrogen or alkyl, which includes, but is not limited to, Ci-20 alkyl, Οχ.χο alkyl, or Οι-g alkyl, R³ is -OR' or -N(R³')2);

(d) R⁴ is hydrogen, Ci-i₀ rent, Ci-i₀ alkyl optionally substituted by a lower alkyl, alkoxy or halogen, Ci-i₀ haloalkyl, C₃-i₀ cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aminoacyl, di(lower alkyl)amino-lower alkyl, aryl, such as phenyl, heteroaryl, such as, pyridinyl, substituted aryl, or substituted heteroaryl;

(e) R⁵ is H, a lower alkyl, CN, vinyl, O(lower alkyl), hydroxyl lower alkyl, that is, (CH₂)_POH, where p is 1-6, including hydroxyl methyl (CH₂OH) , CH₂F, N₃, CH₂CN, CH₂NH₂, CH₂NHCH₃, CH₂N(CH₃)₂, alkyne (optionally substituted), or halogen, including F, Cl, Br, or I, with the proviso that when X is OH, base is cytosine and R⁶ is H, R⁵ it cannot be N3 and when X is OH, R⁶is CH3 or CH₂F and 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, Ci-4 alkyl, C₂*₄ alkenyl, C₂-₄alkynyl, vinyl, N₃, CN, Cl, Br, F, I, NO₂, OC(O)O(Ci-₄alkyl), OC(O)O(C₂.₄ alkyl), OC(O)O(C₂.₄ alkynyl), OC (O) O (OCi-io alkenyl), Cx-io haloalkyl, O (aminoacyl),

98/967

O(Ci-4 acyl) , O(C₂_₄ alkyl), O(Ci-₄ alkenyl) , S(Ci.₄ acyl) , S(C₂.₄ rent), S(C₂_₄ alkynyl) , S(C_X-₄ alkenyl), SO(Ci-₄ acyl), SO(C₂.₄ alkyl), SO(C₂.₄ alkynyl), SO₂(Ci-₄acyl), SO₂(Cl-4 alkyl), SO₂(C₂_₄ alkynyl), SO₂ (C₂.₄alkenyl), OS(O)₂(C₁.₄ acyl), OS(O)₂(C!.₄ rent), OS(O)₂(C₂-₄ alkenyl), NH₂, NH(Ci-₄ alkyl), NH(C₂.₄alkenyl), NH(C₂_₄ alkynyl), NH(Ci-₄ acyl), N(C_x-₄rent)₂, N(Ci-i_Yes acyl)₂, in which alkyl, alkynyl, alkenyl and vinyl are optionally substituted by N₃, CN, one to three halogens (Cl, Br, F, I), N0₂, C(O)O(Ci-₄alkyl), C(O)O(C₁_₄ alkyl), C(O)O(C₂-₄ alkynyl), C(O)O(C₂.₄ alkenyl), 0(C_x-₄ acyl), 0(Ci-₄ rent), 0(C₂.₄alkenyl), S(Ci-₄ acyl), S(C_X-₄ rent), S(C₂₄ alkynyl), S(C₂.₄ alkenyl), SO(Ci-₄ acyl), SO(Ci-₄ alkyl), SO(C₂.₄alkynyl), SO(C₂.₄ alkenyl), SO₂(Ci-₄ acyl), SO₂(Ci-₄rent), SO₂(C₂.₄ alkynyl), SO₂(C₂.₄ alkenyl), OS(O)₂(C.₄acyl), OS(O)₂(Ci-₄ rent), OS(O)₂(C₂-₄ alkenyl), NH₂, NH(Ci-₄ alkyl), NH(C₂.₄ alkenyl), NH(C₂_₄ alkynyl), NH(Ci-4 acyl), N(Ci-₄ rent)₂, N(Ci.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';

where R' is lower alkyl, lower cycloalkyl or C(0)(lower alkyl) or, alternatively, in the case of NR'₂, each R' ccomprises at least one C atom that is linked to form a heterocycle that comprises at least two carbon atoms; and (j ) Z is N or CR¹²; and

R¹² is a H, halogen (including F, Cl, Br, I), OR', NH₂, NHR', NR'₂, NO₂, lower alkyl of Ci~C₆, CO₂R', CONH₂, CONHR', CONR'2, CH=CHCO₂H, or CH=CHCO₂R'; with the

99/967 condition that when the base is represented by the structure c with R¹¹ being hydrogen, R¹² is not one: (i) C=CH, (ii) -C=CH₂, or (iii) -NO₂.

The seventh aspect of the fourth modality is directed to the compound represented by formula 1-8:

where (a) R¹ is hydrogen, methyl, ethyl, n-propyl, ipropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b) R² is hydrogen or CH₃ ;

(c) R^3rd is H and R^3b 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, sh(oh)sh₃, CH₂ ((4'-OH)-Ph), CH₂SH, or lower cycloalkyl;

(d) R⁴ is hydrogen, CH₃, And,^xYes,ⁿYes,ⁿBu, 2-butyl,^cBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methylpiperidin-4-yl, halolower alkyl, di(lower alkyl)amino-lower alkyl;

(e) R⁵ is H, CN, CH3, OCH3, CH2OH, CH2F, halogen, including F, Cl, Br or I, with the proviso that when X is OH, R^yes is CH3 or CH₂F, R⁵ cannot be H;

(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';

100/967 where R' is lower alkyl, lower cycloalkyl or C(O)(lower alkyl) or, alternatively, in the case of NR'2, each R' ccomprises at least one C atom which is linked to form a heterocycle comprising at least two carbon atoms; and (j ) Z is N or CR¹²; and

R¹² is a H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, N02, Ci-C6 lower alkyl, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R'; with the condition that R¹² is not one: (i) -C^CH, (ii) -C=CH2, or (iii) -NO₂.

The eighth aspect of the fourth modality is directed to the compound represented by formula 1-8:

where (a) R¹ is hydrogen, methyl, ethyl, n-propyl, ipropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b) R² is hydrogen or CH₃;

(C) R^3rd is H and R^3b is H, CH₃, CH(CH₃)₂, CH₂CH(CH₃)₂, CH (CH₃) CH₂CH₃, CH₂Ph, or lower cycloalkyl;

(d) R⁴ is hydrogen, CH₃, And,¹Yes,ⁿYes,ⁿBu, 2-butyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methylpiperidin-4-yl, halolower alkyl, di(lower alkyl)amino-lower alkyl;

(e) R⁵ is H, CN, CH2F, F, Cl, Br, or I; with the condition that X is OH, R⁶ is CH3 or CH₂F, R⁵ cannot be H;

(f) R⁶ is H, CH₃, CH₂F, CHF₂, CF₃ or F;

(g) X is H, OH, F, OCH₃, F, Cl, Br, I, NH₂ or N₃;

101/967 (h) Y is H, OH, CH₃, F, Cl, Br, I, NH₂ or N₃, OCH₃ or OC (0) CH₃ ;

(i) R¹⁰ is H, F, Br, I, OH, OR', NH₂, NHR', NR'₂,

CO₂R', CONH₂, CONHR', CONR'₂, CH=CHCO₂H, or CH=CHCO₂R';

where R' is lower alkyl, lower cycloalkyl or C(O)(lower alkyl) or, alternatively, in the case of NR'₂, each R' ccomprises at least one C atom that is linked to form a heterocycle that comprises at least two carbon atoms; and (j) Z is N or CR¹²; and

R¹² is a H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, Cx-C6 lower alkyl, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R'; with the condition that R¹² is not one: (i) -C^CH, (ii) -C=CH2, or (iii) -NO₂The ninth aspect of the fourth modality is directed to the compound represented by formula 1-8:

where (a) R¹ is hydrogen, methyl, ethyl, n-propyl, ipropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b) R² is hydrogen;

(C) R^3rd is H and R^3b is H, CH₃, CH(CH₃)₂, CH₂CH(CH₃)₂, CH (CH₃) CH₂CH₃, CH₂Ph, or lower cycloalkyl;

(d) R⁴ is hydrogen, CH₃, And,¹Yes,ⁿYes,ⁿBu, 2-butyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methylpiperidin-4-yl, halolower alkyl, di(lower alkyl)amino-lower alkyl;

102/967 (e) R⁵ is H, with the condition that, when X is OH, R^yesis CH₃ or CH₂F, 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';

where R' is lower alkyl, lower cycloalkyl or C(O)(lower alkyl) or, alternatively, in the case of NR'₂, each R' ccomprises at least one C atom which is linked to form a heterocycle comprising at least two carbon atoms,· and (j ) Z is N or CR¹²; and

R¹² is a H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR' 2, NO2, Ci-C6 lower alkyl, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R'; with the condition that R¹² is not one: (i) -C=CH, (ii) -C=CH2, or (iii) -NO₂.

The tenth aspect of the fourth modality is directed to the compound represented by formula 1-8:

where (a) R¹ is hydrogen, methyl, phenyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b) R² is hydrogen;

(c) R^3rd is H and R^3b is H, CH₃, CH(CH₃)₂, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, CH₂Ph, or lower cycloalkyl;

(d) R⁴ is hydrogen, CH₃, And,^xYes,ⁿYes,ⁿBu, 2-butyl,^bBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl

103/967 Piperidin-4-yl, halolower alkyl, di(lower alkyl)amino-lower alkyl;

(e) R⁵ is H, with the condition that, when X is OH, R⁶is CH₃ or CH₂F, R⁵ it cannot be Η;

(f) R^yes 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=CHCO₂R¹ ;

where R' is lower alkyl, lower cycloalkyl or C(O)(lower alkyl) or, alternatively, in the case of NR'₂, each R' ccomprises at least one C atom that is linked to form a heterocycle that comprises at least two carbon atoms; and (j) Z is N or CR¹²; and

R¹² is a H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, Ci-C6 lower alkyl, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R'; with the condition that R¹² is not one: (i) -C=CH, (ii) -C=CH2, or 20 (iii) -NO₂.

A fifth embodiment of the invention is directed to the compound represented by formula I in which the base is a structure represented by formula d above, where R¹, R², R^3rd, R^3b, R⁴, R⁵, R⁶, X and Y are defined in the Summary of the Invention section above.

The first aspect of the fifth modality is directed to the compound represented by formula 1-9:

104/967

<img file="BRPI0809654A2_D0013.tif" />

where (a) R¹ is hydrogen, n-alkyl; branched alkyl; cycloalkyl; or aryl, which includes, but is not limited to, phenyl or naphthyl, wherein phenyl or naphthyl is optionally substituted with at least one of Ci-6 alkyl, C2.s alkenyl, C2-6 alkynyl, Ci-6 alkoxy, F, Cl, Br, I, nitro, cyano, Ci-s haloalkyl, -N(R¹')2, Cx-β acylamino, -NHSO₂Ci-₆rent, -SO₂N(R¹')2, COLOR¹, and -SO2Ci-₆ rent; (R¹' is independently hydrogen or alkyl, which includes, but is not limited to, C1-20 alkyl, C1-10 alkyl, or C1-6 alkyl, R¹ is -OR' or -N(R¹')2);

(b) R² is hydrogen or CH₃;

(c) R^3rd and R^3b are (i) independently selected from hydrogen, Ci-10 alkyl, cycloalkyl, - (CH2) c (NR³') 2, Ci-β hydroxyalkyl, -CH₂SH, - (CH₂) ₂S (O) dMe, (CH2)3NHC(=NH)NH₂, (1H-indol-3-yl)methyl, (1H-imidazol-4yl)methyl, - (CH₂) eCOR³, aryl and aryl C_x-₃ alkyl, said aryl groups optionally substituted by a group selected from hydroxyl, Ci-i₀ rent, Ci-₆ alkoxy, halogen, nitro and cyano; (ii) R^3rd and R^3b both are C 1-6 alkyl; (iii) R^3rd and R^3b together they are (CH2)f so as to form a spiro ring; (iv) R^3rd is hydrogen and R^3b and R² together they are

105/967 (CH₂) n so as to form a cyclic ring that includes the adjacent atoms N and C (v) R^3b is hydrogen and R^3rd and R²together are (CH2)n so as to form a cyclic ring that includes the adjacent atoms N and C, where c is 1 to 6, déOa 2, eé0a3, f is 2 to 5, n is 2 to 4, and where R³' is independently hydrogen or Cx-_and rent and R³ is -OR' or -N(R³')2); (vi) R^3rd is H and R^3b 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)NH_2zCH₂CH₂CH₂CH₂NH₂, -CH₂CH₂CH₂NHC(NH)NH_2z CH₂-Imidazol~4-yl, CH₂OH, CH(OH)CH_3rd CH₂ ((4'-OH)-Ph) , CH₂SH, OR lower cycloalkyl; or (viii) R^3rd 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)NH_2z ch₂ch₂ch₂ch₂nh₂,

CH₂CH₂CH₂NHC(NH)NH₂, CH₂-imidazol-4-yl, CH₂OH, CH(OH)CH₃,

CH₂ ( (4 '-OH)-Ph) , CH₂SH, or lower cycloalkyl and R^3b is H, where R³' is independently hydrogen or alkyl, which includes, but is not limited to, Cx-2o alkyl, Ci-10 alkyl, or Cx-6 alkyl, R³ is -OR' or -N(R³')2);

(d) R⁴ is hydrogen, Ci-i₀ alkyl, Ci-io alkyl optionally substituted by a lower alkyl, alkoxy or halogen, Ci-i₀ haloalkyl, C₃.₁₀ cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aminoacyl, di(lower alkyl)amino-lower alkyl, aryl, such as phenyl, heteroaryl, such as, pyridinyl, substituted aryl, or substituted heteroaryl;

(e) R⁵ is H, a lower alkyl, CN, vinyl, O(lower alkyl), hydroxyl lower alkyl, that is, (CH₂)_POH, where p is 1-6, including hydroxyl methyl (CH₂OH) , CH₂F, N₃, CH₂CN, CH₂NH₂, CH₂NHCH₃, CH₂N(CH₃)₂, alkyne

106/967 (optionally substituted), or halogen, including F, Cl, Br, or I, with the proviso that when X is OH, the base is cytosine and R⁶ is H, R⁵ it cannot be N3 and when X is OH, R⁶is CH3 or CH₂F and 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, Ci-4 alkyl, C₂_₄ alkenyl, C₂.₄alkynyl, vinyl, N₃, CN, Cl, Br, F, I, NO₂, ΟΟ(Ο)Ο(Οχ.₄alkyl), OC (O) O (Ci-₄ alkyl), OC(O)O(C₂.₄ alkynyl), OC(O)O(C₂-₄ alkenyl), OCx-₁₀ haloalkyl, O (aminoacyl), 0(Cx-xo acyl), Ο (Οχ.₄ alkyl), O(C₂.₄ alkenyl), S(Cx-₄acyl), S(Cx-₄ rent), S(C₂.₄ alkynyl), S(C₂.₄ alkenyl), S0(Cx-4 acyl), SO(Cx-₄ alkyl), SO(C₂.₄ alkynyl), SO(C₂.₄alkenyl), SO₂(Cx-₄ acyl), SO₂(Cx-₄ rent), SO₂(C₂.₄alkynyl), SO₂(C₂.₄ alkenyl), OS(O)₂(Cx-₄ acyl), OS(O)₂(Cx-4 alkyl), OS(O)₂(C₂.₄ alkenyl), NH₂, ΝΗ(0χ.₄alkyl), NH(C₂_₄ alkenyl), NH(C₂-₄ alkynyl), ΝΗ(Οχ_₄acyl), N(Cx-₄ rent)₂, N(C1-18 acyl)₂, in which alkyl, alkynyl, alkenyl and vinyl are optionally substituted by N₃, CN, one to three halogens (Cl, Br, F, I), N0₂, C(0)0(Ci-4 alkyl), 0(0)0(0χ_₄ alkyl), C(O)O(C₂.₄alkynyl), C(O)O(C₂.₄ alkenyl), 0(0χ_₄ acyl), 0(0χ_₄alkyl), O(C₂.₄ alkenyl), 3(0χ.₄ acyl), S(Cx-₄ rent), S(C₂_₄ alkynyl), S(C₂.₄ alkenyl), SO(Cx-₄ acyl), SO(Cx-₄alkyl), SO(C₂.₄ alkynyl), SO(C₂.₄ alkenyl), SO₂(Cx-₄acyl), SO₂(Cx-₄ rent), S0₂ (C₂.₄ alkynyl), S0₂ (C₂.₄alkenyl), OS(O)₂(Cx-₄ acyl), OS(O)₂(Cx-₄ rent), OS(O)₂(C₂.₄ alkenyl), NH2, ΝΗ(Οχ.₄ alkyl), NH(C₂.₄alkenyl), NH(C₂.₄ alkynyl), ΝΗ(0χ_₄ acyl), N(Οχ.₄rent)₂, N(Ox.₄ acyl)₂;

107/967

The second aspect of the fifth modality is directed to the compound represented by formula 1-9:

where (a) R¹ is hydrogen, methyl, ethyl, n-propyl, ipropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b) R² is hydrogen or CH₃;

(c) R^3rd is H and R^3b 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;

(d) R⁴ is hydrogen, CH₃, And,^andYes,ⁿYes,ⁿBu, 2-butyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methylpiperidin-4-yl, halolower alkyl, di(lower alkyl)amino-lower alkyl;

(e) R⁵ is H, CN, CH3, OCH3, CH2OH, CH2F, halogen, including F, Cl, Br or I, with the proviso that when X is OH, R⁶ is CH3 or CH₂F, R⁵ cannot be H;

(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;

The third aspect of the fifth modality is directed to the compound represented by formula 1-9:

where (a) R¹ is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl,

108/967 ) p-fluorophenyl; J (b) R² is hydrogen or CH₃ ;

(c) R^3rd is H and R^3b is H, CH₃, CH(CH₃)₂, CH₂CH(CH₃)_2zCH (CH₃) CH₂CH₃, CH₂Ph, or lower cycloalkyl,· (d) R⁴ is hydrogen, CH₃, And,^xYes,ⁿYes,ⁿBu, 2-butyl,^cBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methylpiperidin-4-yl, halolower alkyl, di(lower alkyl)amino-lower alkyl;

(e) R⁵ is H, CN, CH2F, F, Cl, Br, or I; with the condition that X is OH, R⁶ is CH3 or CH₂F, R⁵ it cannot be Η;

(f) R⁶ is H, CH₃, CH₂F, CHF_2z CF₃ OR F;

(g) X is Η, OH, F, OCH₃, F, Cl, Br, I, NH₂ OR N₃ ;

(h) Y is H, OH, CH₃, F, Cl, Br, I, NH₂, N₃, OCH₃ or OC(O)CH₃;

The fourth aspect of the fifth modality is directed to the compound represented by formula 1-9:

where (a) R¹ is hydrogen, methyl, ethyl, n-propyl, ipropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b) R² is hydrogen;

(c) R^3rd is H and R^3b is H, CH₃, CH(CH₃)₂, CH₂CH(CH₃)₂, CH (CH₃) CH₂CH₃, CH₂Ph, or lower cycloalkyl;

(d) R⁴ is hydrogen, CH₃, Et, ^r,ⁿYes,ⁿBu, 2-butyl,^andBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methylpiperidin-4-yl, lower haloalkyl, di(alkyl

109/967 lower)amino-lower alkyl;

<td>(and)</td><td>R⁵ is H, with the proviso that, when X is OH, R'</td>

<td>is CH₃ or</td><td>CH₂F, R⁵ cannot be H;</td>

<td>(f)</td><td>R⁶ is H, CH₃, CH₂F, CHF₂, CF₃ or F;</td>

<td>(g)</td><td>X is H, OH, OCH₃, F, NH₂ OR N₃;</td>

(h) Y is OH, NH_Z, OCH₃ OR OC(O)CH₃;

The fifth aspect of the fifth modality is directed to the compound represented by formula 1-9:

where (a) R¹ is hydrogen, methyl, phenyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b) R² is hydrogen;

(c) R^3rd is H and R^3b is H, CH₃, CH(CH₃)₂, CH₂CH(CH₃)₂, CH (CH₃) CH₂CH₃, CH₂Ph, or lower cycloalkyl;

(d) R⁴ is hydrogen, CH₃, And,⁴Yes,ⁿYes,ⁿBu, 2-butyl,^fcBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methylpiperidin-4-yl, halolower alkyl, di(lower alkyl)amino-lower alkyl;

(e) R⁵ is H, with the condition that, when X is OH, R^andis CH₃ or CH₂F, 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 sixth aspect of the fifth modality is directed to the compound represented by the formula 1-10:

110/967

<img file="BRPI0809654A2_D0014.tif" />

1-10 where (a) R¹ is hydrogen, methyl, ethyl, n-propyl, ipropyl or a substituted or unsubstituted phenyl, where the substituent of the substituted phenyl is at least one of CH₃, OCH₃, F, Cl, Br, I, nitro, cyano and a CH₃__whatX_what, where X is F, Cl, Br or I eq ê 1-3;

(b) R² is hydrogen or CH₃;

(c) R^3rd is H and R^3b 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 R^3rd is CH3, CH(CH₃)₂, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, CH₂Ph, CH₂-indol-3yl, -CH₂CH₂SCH₃, CH₂CO₂H, CH₂C(O)NH₂, CH₂CH₂COOH, CH₂CH₂C(O)NH₂, ch₂ch₂ch₂ch₂nh₂, -CH₂CH₂CH₂NHC(NH)NH₂, ch₂irnidazol-4-yl, CH₂OH, CH(OH)CH₃, CH₂ ( (4 ' -OH)-Ph) , CH₂SH, or lower cycloalkyl and R^3b is H;

(d) R⁴ is hydrogen, CH₃, And,^xYes,ⁿYes,ⁿBu, 2-butyl,^fcBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methylpiperidin-4-yl, lower haloalkyl, di(alkyl

111/967 lower)amino-lower alkyl;

(e) R⁵ is H, CN, CH3, OCH3, CH2OH, CH2F, N3, CH2CN, CH2N3, CH2NH2, CH2NHCH3, CH2N(CH3)2, halogen, including F, Cl, Br, or I, with the proviso that when X is OH, R⁶ is CH3 or CH₂F, 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, NHCHj, NH(vinyl), NH(acetyl), NH(C(O)CH₃), N(CH₃)₂, N(C(O)CH₃)₂ or 0 (aminoacyl);

The seventh aspect of the fifth modality is directed to the compound represented by the formula 1-10:

where (a) R¹ is hydrogen, methyl, ethyl, n-propyl, ipropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b) R² is hydrogen or CH₃;

(c) R^3rd is H and R^3b 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;

(d) R⁴ is hydrogen, CH₃, Et, ^r,ⁿYes,ⁿBu, 2-butyl,^cBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methylpiperidin-4-yl, halolower alkyl, di(lower alkyl)amino-lower alkyl;

(e) R⁵ is H, CN, CH₃, OCH_3z CH₂OH, CH₂F, halogen, including F, Cl, Br or I, with the proviso that when X is OH

112/967, R⁶ is CH₃ or CH₂F, R⁵ it cannot be Η;

<td>(f)</td><td>R⁶ is H, CH₃</td><td>, CH₂F, chf₂,</td><td>cf₃,</td><td>F,</td><td>OR CN;</td>

<td>(g)</td><td>X is H, OH,</td><td>F, 0CH₃, Cl,</td><td>Br,</td><td>I,</td><td>NH₂ OR N₃; and</td>

<td>(h)</td><td>Y is OH, H,</td><td>CH₃, vinyl,</td><td>nh₂,</td><td>n₃</td><td>, CN, Cl, Br, F, I,</td>

<td>OC(O) CH₃,</td><td>OCH₃;</td><td></td><td></td><td></td><td></td>

The eighth aspect of the fifth modality is directed to the compound represented by the formula 1-10:

where (a) R¹ is hydrogen, methyl, ethyl, n-propyl, ipropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl, (b) R² is hydrogen or CH₃;

(c) R^3rd is H and R^3b is H, CH₃, CH(CH₃)₂, CH₂CH(CH₃)₂, CH(CH₃) CH₂CH₃, CH₂Ph, or lower cycloalkyl;

(d) R⁴ is hydrogen, CH₃, And,¹Yes,ⁿYes,ⁿBu, 2-butyl,^cBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methylpiperidin-4-yl, halolower alkyl, di(lower alkyl)amino-lower alkyl;

(e) R⁵ is H, CN, CH2F, F, Cl, Br, or I; with the condition that X is OH, R⁶ is CH3 or CH₂F, R⁵ cannot be H;

(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;

The ninth aspect of the fifth modality is directed to the compound represented by formula 1-10:

where (a) R¹ is hydrogen, methyl, ethyl, n-propyl, i

113/967 propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b) R² is hydrogen;

(c) R^3rd is H and R^3b is H, CH₃, CH(CH₃)₂, CH₂CH(CH₃)₂, CH (CH₃) CH₂CH_3z CH₂Ph, or lower cycloalkyl;

(d) R⁴ is hydrogen, CH₃, And,^xYes,ⁿYes,ⁿBu, 2-butyl,^bBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methylpiperidin-4-yl, halolower alkyl, di(lower alkyl)amino-lower alkyl;

(e) R⁵ is H, with the condition that, when X is OH, R^yesis CH₃ or CH₂F, R⁵ it cannot be Η;

(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 tenth aspect of the fifth modality is directed to the compound represented by the formula 1-10:

where (a) R¹ is hydrogen, methyl, phenyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b) R₂ is hydrogen;

(c) R^3rd is H and R^3b is H, CH₃, CH(CH₃)₂, CH₂CH(CH₃)₂, CH (CH₃) CH₂CH₃ , CH₂Ph, or lower cycloalkyl;

(d) R⁴ is hydrogen, CH₃, And,^xYes,ⁿYes,ⁿBu, 2-butyl,^bBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methylpiperidin-4-yl, halolower alkyl, di(lower alkyl)amino-lower alkyl;

114/967 (e) R⁵ is H, with the condition that, when X is OH, R⁶and CH₃ or CH₂F, R 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 following tables contain numeric identifiers associated with different placeholder designators that should be viewed based on the accompanying structure. These structures contemplate species of 10 different aspects of the disclosed modalities and are not intended to restrict every contemplated compound represented by the structure of formula I. However, it is contemplated that any exemplified nucleoside base may be used in combination with any contemplated species that specifies a particular combination of R¹, R², R^3rd, R^3b, R⁴, R⁵, R^yes, X and Y. In each of the tables presented, the phosphoramidate substituent containing the substituents R^3rdand R^3b is shown without reference to the stereochemical structure (cf. structures 1-1, 1-3, 1-5, 1-7 and 1-9 above).

The compounds mentioned below are considered to incorporate compounds in which R^3rd projects towards the observer, while R^3b it projects in the opposite direction to the observer (cf. structures 1-2, 1-4, 1-6, 1-8 and 1-10). In addition, it is considered that the compounds mentioned below also include compounds in which R^3rd projects in a direction opposite to the observer, while R^3b projected towards the observer. Without limitation, however, preferred compounds are considered to be those in which R^3rd projects towards the observer and R^3b projects in the opposite direction to the observer, so that the S-configuration of the amino acid

115/967

L be presented. In addition, the inventors recognize that the phosphorus atom of the phosphoramidate moiety is another source of chirality. Although the structures below do not specifically show chirality at phosphorus, the inventors recognize that stereochemical configurations are possible such that in a scale-line (or zig-zag) structure the oxo-substituent projects toward the observer, while the OR-substituent¹projects in a direction opposite to the observer and vice versa, that is, where the Cahn-Ingold-Prelog stereochemical designation of phosphoto is both R and S.

Therefore, the structures below include all possible stereochemical configurations for phosphorus.

R⁹

<img file="BRPI0809654A2_D0015.tif" />

II

Table II-1.

<td></td><td>R¹</td><td>R²</td><td>R^3rd</td><td>R^3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>II-ll</td><td>ch₃</td><td>H</td><td>H</td><td>H</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-1-2</td><td>ch₃</td><td>H</td><td>H</td><td>ch₃</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-1-3</td><td>ch₃</td><td>H</td><td>H</td><td>CH(CH₃)₂</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-1-4</td><td>ch₃</td><td>H</td><td>H</td><td>CH₂CH(CH₃)₂</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-1-5</td><td>CH3</td><td>H</td><td>H</td><td>CH₂Ph</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-1-6</td><td>ch₃</td><td>H</td><td>H</td><td>CH₂-indole-3-yl</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

116/967

<td>No!</td><td>R¹</td><td>R²</td><td>R^3rd</td><td>R^3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R®</td><td>R⁹</td>

<td>II-1-7</td><td>ch₃</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-1-8</td><td>ch₃</td><td> *</td><td>H</td><td> *</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

*R² and R^3b linked together by (CH₂)₃ to form a five-membered ring.

Table II-2.

<td>No!</td><td>R¹</td><td>R²</td><td>R^3rd</td><td>R3b</td><td>R⁴</td><td>R^yes</td><td>R^and</td><td>X</td><td>And</td><td>R⁷</td><td>R®</td><td>R⁹</td>

<td>II-2-1</td><td>You</td><td>H</td><td>H</td><td>H</td><td>ch₃</td><td>H</td><td>CH₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-2-2</td><td>You</td><td>H</td><td>H</td><td>ch₃</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-2-3</td><td>You</td><td>H</td><td>H</td><td>CH(CH₃)₂</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-2-4</td><td>You</td><td>H</td><td>H</td><td>ch₂ch(ch₃)₂</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-2-5</td><td>You</td><td>H</td><td>H</td><td>CH₂Ph</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-2-6</td><td>You</td><td>H</td><td>H</td><td>CH₂-indole-3-</td><td>CH island₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-2-7</td><td>You</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-2-8</td><td>You</td><td> *</td><td>H</td><td> *</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>*R² and R</td><td>3b</td><td colspan="2">linked</td><td>together for</td><td>(ch₂)₃ ]</td><td>for</td><td colspan="2">form</td><td colspan="2">ring</td><td>from</td><td></td>

five members.

Table II-3.

<td>w</td><td>R¹</td><td>R²</td><td>R^3rd</td><td>R^3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R®</td><td>R⁹</td>

<td>II-3-1</td><td>^JP</td><td>H</td><td>H</td><td>H</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-3-2</td><td>IP_r</td><td>H</td><td>H</td><td>ch₃</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-3-3</td><td>IP_r</td><td>H</td><td>H</td><td>CH(CH₃)₂</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-3-4</td><td>ip_r</td><td>H</td><td>H</td><td>CH₂CH(CH₃j₂</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-3-5</td><td>1 P*</td><td>H</td><td>H</td><td>CH₂Ph</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-3-6</td><td>³P</td><td>H</td><td>H</td><td>CH₂-indole-3-yl</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-3-7</td><td>^xP</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-3-8</td><td>¹ P</td><td> *</td><td>H</td><td> *</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

*R² and R^3b linked together by (CH₂)₃ to form a five-membered ring.

Table II-4.

117/967

<td>No</td><td>R¹</td><td>R²</td><td>_R3rd</td><td>R^3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R'</td><td>' R⁸</td><td>R⁹</td>

<td>II-4-1</td><td>^[Boo</td><td>H</td><td>H</td><td>H</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-4-2</td><td>⁶Boo</td><td>H</td><td>H</td><td>ch₃</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-4-3</td><td>^fcBoo</td><td>H</td><td>H</td><td>CH(CH₃)₂</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-4-4</td><td>^fcBoo</td><td>H</td><td>H</td><td>CH₂CH(CH₃) ₂</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-4-5</td><td>^fcBoo</td><td>H</td><td>H</td><td>CH₂Ph</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-4-6</td><td>^yesBoo</td><td>H</td><td>H</td><td>CH₂-indole-3</td><td>-ila CH₃</td><td>H</td><td>cr₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-4-7</td><td>^fcBoo</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-4-8</td><td>^andBoo</td><td> *</td><td>H</td><td> *</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>*R² and R</td><td colspan="3">^3b linked</td><td>together for</td><td colspan="2">(CH₂)₃ for</td><td colspan="2">form</td><td colspan="2">ring</td><td>from</td><td></td>

five members.

Table II-5.

<td>N'</td><td>R¹</td><td>R²</td><td>_R3rd</td><td>_R3b</td><td>R⁴</td><td>R^yes</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>II-5-1</td><td>Ph</td><td>H</td><td>H</td><td>H</td><td>ch₃</td><td>The</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-5-2</td><td>Ph</td><td>H</td><td>H</td><td>CH₃</td><td>ch₃</td><td>The</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-5-3</td><td>Ph</td><td>H</td><td>H</td><td>CH(CH₃)₂</td><td>ch₃</td><td>The</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-5-4</td><td>Ph</td><td>H</td><td>H</td><td>CH₂CH(CH₃)₂</td><td>ch₃</td><td>The</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-5-5</td><td>Ph</td><td>H</td><td>H</td><td>CH₂Ph</td><td>ch₃</td><td>The</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-5-6</td><td>Ph</td><td>H</td><td>H</td><td>CH₂-indole-3-yl</td><td>ch₃</td><td>The</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-5-7</td><td>Ph</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td></td><td>The</td><td></td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-5-8</td><td>Ph</td><td> *</td><td>H</td><td> *</td><td>ch₃</td><td>The</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>*R² and five Table</td><td colspan="4">R^3b linked together by (CH₂members. . II-6.</td><td colspan="2"> ) ₃ for</td><td colspan="2">form</td><td colspan="3">ring of</td><td></td>

<td>N'</td><td>R¹</td><td></td><td>R²</td><td>rj 3 a. τί 3b Ix. Xx</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>II-6- 1</td><td>p-me Ph</td><td> -</td><td>H</td><td>H H</td><td>ch₃</td><td>The</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-6- 2</td><td>p-me Ph</td><td></td><td>H</td><td>H CH₃</td><td>ch₃</td><td>The</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-6-</td><td>p-me</td><td> -</td><td>H</td><td>H CH(CH₃)₂</td><td>ch₃</td><td>The</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

118/967

<td>N»</td><td>R¹</td><td>R²</td><td>R^3rd</td><td>_R3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R³</td><td>R⁹</td>

<td> 3</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>XI-6-</td><td>p-Me-</td><td>H</td><td>H</td><td>CH₂CH(CH₃)₂</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>NH₂</td>

<td> 4</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>XI-6-</td><td>p-Me-</td><td>H</td><td>H</td><td>CH₂Ph</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 5</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>XI-6-</td><td>p-Me-</td><td>H</td><td>H</td><td>CH₂-indole-3-</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 6</td><td>Ph</td><td></td><td></td><td>island</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>IT-6-</td><td>p-Me-</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 7</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>XI-6-</td><td>p-Me-</td><td> *</td><td>H</td><td> *</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 8</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>*R² and</td><td colspan="4">R^3b linked together by (CH₂)</td><td colspan="2">3 for</td><td colspan="2">form</td><td>ring</td><td>from</td><td></td><td></td>

<td>five</td><td colspan="2">members.</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td colspan="2">Table II-7.</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td></td><td>R¹</td><td>R²</td><td>_R3rd</td><td>R^3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>r₈</td><td>R⁹</td>

<td>XI-7-</td><td>pF-</td><td>H</td><td>H</td><td>H</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 1</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>XI-7-</td><td>pF-</td><td>H</td><td>H</td><td>ch₃</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 2</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>XI-7-</td><td>pF-</td><td>H</td><td>H</td><td>CH(CH₃)₂</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 3</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>XI-7-</td><td>pF-</td><td>H</td><td>H</td><td>CH₂CH(CH₃)₂</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 4</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>XI-7-</td><td>pF-</td><td>H</td><td>H</td><td>CH₂Ph</td><td>ch₃</td><td>H</td><td>CH3</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 6</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>XI-7-</td><td>pF-</td><td>H</td><td>H</td><td>CH₂-indole-3-</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 7</td><td>Ph</td><td></td><td></td><td>island</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>XI-7-</td><td>pF-</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

Ph

119/967

<td>N'</td><td>R¹</td><td>R²</td><td>_R3rd</td><td>R^3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>II-7-</td><td>pF-</td><td> ★</td><td>H</td><td> *</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 20</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>*R² and</td><td colspan="4">R^3b linked together by (CH₂)</td><td colspan="2">3 for</td><td colspan="2">form</td><td>ring</td><td>from</td><td></td><td></td>

<td>five</td><td colspan="2">members.</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td colspan="2">Table II-8.</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>N'</td><td>R¹</td><td>R²</td><td>_R3rd</td><td>_R3b</td><td>R⁴</td><td>R⁵</td><td>R^yes</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>II-8-</td><td>p-Cl-</td><td>H</td><td>H</td><td>H</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 1</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-8-</td><td>p-Cl-</td><td>H</td><td>H</td><td>ch₃</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 2</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td> 11-8“</td><td>p-Cl-</td><td>H</td><td>H</td><td>CH(CH₃) 2</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 3</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-8-</td><td>p-Cl-</td><td>H</td><td>H</td><td>CH₂CH(CH₃)₂</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 4</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-8-</td><td>p-Cl-</td><td>H</td><td>H</td><td>CH₂Ph</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 5</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-8-</td><td>p-Cl-</td><td>H</td><td>H</td><td>CH₂-indole-3-</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 6</td><td>Ph</td><td></td><td></td><td>ilcl</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-8-</td><td>p-Cl-</td><td>H</td><td>H</td><td>ch₂ch₂school₃</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 7</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-8-</td><td>p-ci-</td><td> ★</td><td>H</td><td> *</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 8</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>*R² and</td><td colspan="4">R^3b linked together by (CH₂)</td><td colspan="2">3 for</td><td colspan="2">form</td><td>ring</td><td>from</td><td></td><td></td>

<td>5 five</td><td colspan="2">members.</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td colspan="2">Table II-9.</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>N'</td><td>R¹</td><td>R²</td><td>R^3rd</td><td>R^3b</td><td>R⁴</td><td>R^yes</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>II - 9 -</td><td>p-Br-</td><td>H</td><td>H</td><td>H</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 1</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-9-</td><td>p-Br-</td><td>H</td><td>H</td><td>ch₃</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

120/967

<td>No</td><td>R¹</td><td>R²</td><td>R^3rd</td><td>R^3b</td><td>R⁴</td><td>R^yes</td><td>_r6</td><td>X</td><td>And</td><td>R⁷</td><td>_r8</td><td>R⁹</td>

<td> 2</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-9- 3</td><td>p-Br- Ph</td><td>H</td><td>H</td><td>CH(CH₃)₂</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-9- 4</td><td>p-Br- Ph</td><td>H</td><td>H</td><td>CH₂CH(CH₃)₂</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-9- 6</td><td>p-Br- Ph</td><td>H</td><td>H</td><td>CH₂Ph</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-9- 7</td><td>p-Br- Ph</td><td>H</td><td>H</td><td>CH₂-indole-3- island</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-9- 8</td><td>p-Br- Ph</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-9- 20</td><td>p-Br- Ph</td><td> ★</td><td>H</td><td> *</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

*R² and R^3b linked together by (CH₂)3 to form a five-membered ring.

<td>N·</td><td>R¹</td><td>R²</td><td>R^3rd</td><td>R^3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>II- 10-1</td><td>pI- Ph</td><td>H</td><td>H</td><td>H</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II- 10-2</td><td>pI- Ph</td><td>H</td><td>H</td><td>ch₃</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II- 10-3</td><td>pI- Ph</td><td>H</td><td>H</td><td>ch(ch₃)₂</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II- 10-4</td><td>pI- Ph</td><td>H</td><td>H</td><td>CH₂CH(CH₃)₂</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II- 10-5</td><td>pI- Ph</td><td>H</td><td>H</td><td>CH₂Ph</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II -</td><td>pI-</td><td>H</td><td>H</td><td>CH₂-indole-3-</td><td>ch₃</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

10-6 Phila

121/967

<td>N^!</td><td>R¹</td><td>r2 j^3a R^3b</td><td>R⁴ R^yes</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>II-</td><td>pI-</td><td>H H CH₂CH₂SCH₃</td><td>ch₃ h</td><td>CH₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 10-7</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II -</td><td>pI-</td><td>*H*</td><td>ch₃ h</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 10-8</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>*R² and</td><td colspan="2">R^3b linked together by</td><td>(CH₂)₃ for</td><td colspan="2">form</td><td>ring</td><td>from</td><td></td><td></td>

five members.

<td>Table</td><td colspan="12">II-11.</td>

<td>No!</td><td>R¹</td><td>R²</td><td>R^3rd</td><td>¹ R^3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>_r8</td><td>R⁹</td>

<td>II-ll-l</td><td>ch₃</td><td>H</td><td>H</td><td>H</td><td>You</td><td>H</td><td>CH₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-11-2</td><td>ch₃</td><td>H</td><td>H</td><td>ch₃</td><td>You</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-11-3</td><td>ch₃</td><td>H</td><td>H</td><td>CH(CH₃)₂</td><td>You</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-11-4</td><td>ch₃</td><td>H</td><td>H</td><td>CH₂CH (CH₃) ₂</td><td>You</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-11-5</td><td>ch₃</td><td>H</td><td>H</td><td>CH₂Ph</td><td>You</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-11-6</td><td>ch₃</td><td>H</td><td>H</td><td>CH₂-indole-3-yl</td><td>You</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-11-7</td><td>ch₃</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td>You</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-11-8</td><td>ch₃</td><td> *</td><td>H</td><td> *</td><td>You</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>*R² and R^:</td><td colspan="3">^3b linked</td><td>together by ÍCH₂)</td><td colspan="2">₃ for</td><td colspan="2">form</td><td colspan="3">ring of</td><td></td>

five members.

Table 11-12.

<td>No!</td><td>R¹</td><td>R²</td><td>R₃to</td><td>R^3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>II-12-1</td><td>You</td><td>H</td><td>H</td><td>H</td><td>You</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-12-2</td><td>You</td><td>H</td><td>H</td><td>ch₃</td><td>You</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-12-3</td><td>You</td><td>H</td><td>H</td><td>ch(ch₃)₂</td><td>You</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-12-4</td><td>You</td><td>H</td><td>H</td><td>CH₂CH(CH₃)₂</td><td>You</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-12-5</td><td>You</td><td>H</td><td>H</td><td>CH₂Ph</td><td>You</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-12-6</td><td>You</td><td>H</td><td>H</td><td>CH₂-indole-3-yl</td><td>You</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-12-7</td><td>You</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td>You</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-12-8</td><td>You</td><td> *</td><td>H</td><td> *</td><td>You</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

*R² and R^3b linked together by (CH₂)₃ to form a ring of

122/967 five members.

<td>N'</td><td>R¹</td><td>R²</td><td>_R3rd</td><td>_R3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>II-13-1</td><td>³P</td><td>H</td><td>H</td><td>H</td><td>You</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-13-2</td><td>³P</td><td>H</td><td>H</td><td>ch₃</td><td>You</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-13-3</td><td>IP_r</td><td>H</td><td>H</td><td>ch(ch₃)₂</td><td>You</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-13-4</td><td>³P</td><td>H</td><td>H</td><td>CH₂CH(CH₃)₂</td><td>You</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-13-5</td><td>¹ P</td><td>H</td><td>H</td><td>CH₂Ph</td><td>You</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-13-6</td><td>³P</td><td>H</td><td>H</td><td>CH₂-indole-3-yl</td><td>You</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-13-7</td><td>ipr</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td>You</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-13-8</td><td>ipr</td><td> *</td><td>H</td><td> *</td><td>You</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

*R² and R^3b linked together by (CH₂)₃ to form a five-membered ring.

Table 11-14.

<td>w</td><td>R¹</td><td>R²</td><td>R 3rd</td><td>R3b</td><td>R⁴</td><td>R^yes</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>II-</td><td>^fcB</td><td>H</td><td>H</td><td>H</td><td>And</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 14-1</td><td>you</td><td></td><td></td><td></td><td>t</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>^fcB</td><td>The</td><td>H</td><td>ch₃</td><td>And</td><td>H</td><td>ch₃</td><td>oh</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 14-2</td><td>you</td><td></td><td></td><td></td><td>t</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>^fcB</td><td>H</td><td>H</td><td>CH(CH₃)₂</td><td>And</td><td>H</td><td>ch₃</td><td>oh</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 14-3</td><td>you</td><td></td><td></td><td></td><td>t</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>^CB</td><td>The</td><td>H</td><td>CH₂CH(CH₃)₂</td><td>And</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 14-4</td><td>you</td><td></td><td></td><td></td><td>t</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>^andB</td><td>H</td><td>H</td><td>CH₂Ph</td><td>And</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 14-5</td><td>you</td><td></td><td></td><td></td><td>t</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>^CB</td><td>H</td><td>H</td><td>CHj-indole-</td><td>And</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 14-6</td><td>you</td><td></td><td></td><td>3 - and the</td><td>t</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td></td><td>H</td><td>H</td><td>ch₂ch₂school₃</td><td>And</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 14-7</td><td>you</td><td></td><td></td><td></td><td>t</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

123/967

<td>Nt</td><td>&lt;r&gt; Shovel CO Shovel 'to' X X kO Shovel LA Shovel Shovel L Shovel CO shovel Shovel 7%</td>

<td>II-</td><td>^rB * Η * EH CH₃ OH OH Η H NH₂</td>

<td> 14-8</td><td>U t</td>

<td>*R² and</td><td>R^3b linked together by (CH₂)₃ to form a ring of</td>

<td>five</td><td>members.</td>

Table 11-15.

<td>No</td><td>R¹</td><td>R²</td><td>_R3rd</td><td>R^3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>II-15-1</td><td>Ph</td><td>H</td><td>H</td><td>H</td><td>You</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-15-2</td><td>Ph</td><td>H</td><td>H</td><td>ch₃</td><td>You</td><td>H</td><td>CH₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-15-3</td><td>Ph</td><td>H</td><td>H</td><td>CH(CH₃)₂</td><td>You</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-15-4</td><td>Ph</td><td>H</td><td>H</td><td>ch₂ch (ch₃ ) ₂</td><td>You</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-15-5</td><td>Ph</td><td>H</td><td>H</td><td>CH₂Ph</td><td>You</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-15-6</td><td>Ph</td><td>H</td><td>H</td><td>CH₂-indole-3-yl</td><td>You</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-15-7</td><td>Ph</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td>You</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-15-8</td><td>Ph</td><td> *</td><td>H</td><td> *</td><td>You</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>*R² and R^:</td><td colspan="3">^3b linked</td><td>together by (CH₂)</td><td colspan="2"> 1₃ for</td><td colspan="2">form</td><td colspan="2">ring</td><td>from</td><td></td>

five members.

Table 11-16.

<td>N^!</td><td>R^x</td><td>R²</td><td>R^3rd</td><td>R^3b</td><td>R⁴</td><td>R^yes</td><td>R^yes</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td> 16-1</td><td>p-Me- Ph</td><td>H</td><td>H</td><td>H</td><td>You</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II- 16-2</td><td>p-Me- Ph</td><td>H</td><td>H</td><td>ch₃</td><td>You</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II - 16-3</td><td>p-Me- Ph</td><td>H</td><td>H</td><td>CH(CH₃)₂</td><td>You</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II- 16-4</td><td>p-Me- Ph</td><td>H</td><td>H</td><td>CH₂CH(CH₃)₂</td><td>You</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II- 16-5</td><td>p-Me- Ph</td><td>H</td><td>H</td><td>CH₂Ph</td><td>You</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

124/967

<td>N^!</td><td>R¹</td><td>R²</td><td>R^3rd</td><td>R^3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>II-</td><td>p-Me-</td><td>H</td><td>H</td><td>CH₂-indole-3-</td><td>You</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 16-6</td><td>Ph</td><td></td><td></td><td>island</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II -</td><td>p-Me-</td><td>H</td><td>H</td><td>ch₂ch₂school₃</td><td>You</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 16-7</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>p-Me-</td><td> *</td><td>H</td><td> *</td><td>You</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 16-8</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>*R² and</td><td colspan="2">R^3b linked</td><td colspan="2">together by (CH₂)</td><td colspan="2">₃ for</td><td colspan="2">form</td><td>ring</td><td>from</td><td></td><td></td>

five members.

Table 11-17.

<td>No!</td><td>R^x</td><td>_r2</td><td>R^3rd</td><td>R^3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td> 11-17- 1</td><td>pF- Ph</td><td>H</td><td>H</td><td>H</td><td>You</td><td>H</td><td>CH₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 11-17- 2</td><td>pF- Ph</td><td>H</td><td>H</td><td>ch₃</td><td>You</td><td>H</td><td>ch₃</td><td>oh</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 11-17- 3</td><td>pF- Ph</td><td>H</td><td>H</td><td>ch(ch₃)₂</td><td>You</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-17 - 4</td><td>pF- Ph</td><td>H</td><td>H</td><td>CH₂CH(CH₃)₂</td><td>You</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 11-17- 5</td><td>pF- Ph</td><td>H</td><td>H</td><td>CH₂Ph</td><td>You</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 11-17- 6</td><td>pF- Ph</td><td>H</td><td>H</td><td>CH₂-indole-3yl</td><td>You</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 11-17- 7</td><td>pF- Ph</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td>You</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 11-17- 8</td><td>pF- Ph</td><td> *</td><td>H</td><td> *</td><td>You</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

*R² and R^3b linked together by (CH₂)₃ to form a five-membered ring.

Table 11-18.

125/96Ί

<td>No!</td><td>R¹</td><td>R² R^2nd R^3b</td><td>R⁴</td><td>R^yes R⁶</td><td>X</td><td>wow CO</td>

<td>II-18-1</td><td>p-Cl-Ph</td><td>H H H</td><td>You</td><td>H CH₃</td><td>OH</td><td>OH Η H NH₂</td>

<td>II-18-2</td><td>p-Cl-Ph</td><td>H H CH₃</td><td>You</td><td>H CH₃</td><td>OH</td><td>OH Η H NH₂</td>

<td>II-18-3</td><td>p-Cl-Ph</td><td>Η H CH(CH₃)₂</td><td>You</td><td>H CH₃</td><td>OH</td><td>OH Η H NH₂</td>

<td>II-18-4</td><td>p-Cl-Ph</td><td>H H CH₂CH(CH₃)₂</td><td>You</td><td>H CH₃</td><td>OH</td><td>OH Η H NH₂</td>

<td>II-18-5</td><td>p-Cl-Ph</td><td>H H CH₂Ph</td><td>You</td><td>H CH₃</td><td>OH</td><td>OH Η H NH₂</td>

<td>II-18-6</td><td>p-Cl-Ph</td><td>H H CH₂-indole-3-</td><td>You</td><td>H CH₃</td><td>OH</td><td>OH Η H NH₂</td>

<td></td><td></td><td>child</td><td></td><td></td><td></td><td></td>

<td>II-18-7</td><td>p-Cl-Ph</td><td>H H CH₂CH₂SCH₃</td><td>You</td><td>H CH₃</td><td>OH</td><td>OH Η H NH₂</td>

<td>II-18-8</td><td>p-Cl-Ph</td><td>*H*</td><td>You</td><td>H CH₃</td><td>OH</td><td>OH Η H NH₂</td>

<td>*R² and R</td><td>^3b linked</td><td>together by (CH₂)₃</td><td>for</td><td>form</td><td colspan="2">ring of</td>

<td colspan="2">five members.</td><td></td><td></td><td></td><td></td><td></td>

<td>Table</td><td> 11-19.</td><td></td><td></td><td></td><td></td><td></td>

<td>Nt</td><td>R¹ R²</td><td>R$^to R^3b</td><td>R⁴ R⁵</td><td>R⁶ X</td><td>And</td><td>R⁷ R⁸ R⁹</td>

<td>II-19-1</td><td>p-Br-Ph H</td><td>H H</td><td>Et H</td><td>ch₃ oh</td><td>OH</td><td>H NH₂</td>

<td>II-19-2</td><td>p-Br-Ph H</td><td>H CH₃</td><td>Et H</td><td>ch₃ oh</td><td>OH</td><td>H NH₂</td>

<td>II-19-3</td><td>p-Br-Ph H</td><td>H CH{CH₃)₂</td><td>Et H</td><td>ch₃ oh</td><td>OH</td><td>H NH₂</td>

<td>II-19-4</td><td>p-Br-Ph H</td><td>H CH₂CH{CH₃)₂</td><td>Et H</td><td>CH₃ OH</td><td>OH</td><td>H NH₂</td>

<td>II-19-5</td><td>p-Br-Ph H</td><td>H CH₂Ph</td><td>Et H</td><td>ch₃ oh</td><td>OH</td><td>H NH₂</td>

<td>II-19-6</td><td>p-Br-Ph H</td><td>H CH₂-indole-3-yl</td><td>Et H</td><td>ch₃ oh</td><td>OH</td><td>H NH₂</td>

<td>II-19-7</td><td>p-Br-Ph H</td><td>H CH₂CH₂SCH₃</td><td>Et H</td><td>ch₃ oh</td><td>OH</td><td>H NH₂</td>

<td>II-19-8</td><td>p-Br-Ph *</td><td>H *</td><td>Et H</td><td>ch₃ oh</td><td>OH</td><td>H NH₂</td>

<td colspan="2">*R² and R^3b linked</td><td>together by (CH₂)₃</td><td>for</td><td>form</td><td colspan="2">ring of</td>

<td colspan="2">5 five members.</td><td></td><td></td><td></td><td></td><td></td>

<td>Table</td><td> 11-20.</td><td></td><td></td><td></td><td></td><td></td>

<td>N·</td><td>R^l R²</td><td>R^3rd R^3b</td><td>R⁴ R</td><td>5 ρ6 V JX L.</td><td>And</td><td>W 00</td>

<td>II-20-1</td><td>pI-Ph H</td><td>H H</td><td>Et H</td><td colspan="3">ch₃ oh oh hh nh₂</td>

<td>II-20-2</td><td>pI-Ph H</td><td>H CH₃</td><td>Et H</td><td colspan="3">CH₃ oh OH η η NH₂</td>

<td>II-20-3</td><td>pI-Ph H</td><td>H CH(CH₃)₂</td><td>Et H</td><td colspan="3">ch₃ oh oh hh nh₂</td>

<td> 11-20-4</td><td>pI-Ph H</td><td>H CH₂CH(CH₃)₂</td><td>Et H</td><td colspan="3">ch₃ oh oh hh nh₂</td>

126/967

<td>N'</td><td>R¹</td><td>R² R^3rd R^3b</td><td>R⁴</td><td>R⁵ R⁶</td><td>X</td><td>And</td><td>W CO dust &lt;£&gt;</td>

<td>II-20-5</td><td>pI-Ph</td><td>H H CH₂Ph</td><td>You</td><td>H CH₃</td><td>OH</td><td>OH</td><td>H NH₂</td>

<td>II-20-6</td><td>pI-Ph</td><td>H H CH₂-indole-3-yl</td><td>You</td><td>H CH₃</td><td>OH</td><td>OH</td><td>H NH₂</td>

<td>II-20-7</td><td>pI-Ph</td><td>H H CH₂CH₂SCH₃</td><td>You</td><td>H CH₃</td><td>OH</td><td>OH</td><td>H NH₂</td>

<td>II-20-8</td><td>pI-Ph</td><td>* H *</td><td>You</td><td>H CH₃</td><td>OH</td><td>OH</td><td>H NH₂</td>

<td>*R² and R</td><td colspan="2">^3b linked together by (CH₂)₃</td><td colspan="4">to form a ring</td><td>from</td>

five members.

Table 11-21.

<td>N'</td><td>R¹</td><td>R²</td><td>p.3a</td><td>_R3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>II-21-1</td><td>ch₃</td><td>The</td><td>The</td><td>The</td><td>ip_r</td><td>The</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-21-2</td><td>ch₃</td><td>The</td><td>The</td><td>ch₃</td><td>IP_r</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-21-3</td><td>ch₃</td><td>The</td><td>The</td><td>ch(ch₃)₂</td><td>'Pr</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-21-4</td><td>ch₃</td><td>The</td><td>The</td><td>CH₂CH(CH₃)₂</td><td>²P</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 11-21-5</td><td>ch₃</td><td>The</td><td>The</td><td>CH₂Ph</td><td>ipr</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-21-6</td><td>ch₃</td><td>The</td><td>The</td><td>CH₂-indole-3-yl</td><td>^IP</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-21-7</td><td>ch₃</td><td>The</td><td>The</td><td>ch₂ch₂school₃</td><td>IP_r</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-21-8</td><td>ch₃</td><td> ★</td><td>The</td><td> *</td><td>IP_r</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

*R² and R^3b linked together by (CH₂)₃ to form a five-membered ring.

Table 11-22.

<td>No</td><td> 1</td><td>R²</td><td>j^3a</td><td>_R3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td> 7</td><td>R⁸</td><td>_r5</td>

<td>II-22-1</td><td>You</td><td>H</td><td>H</td><td>H</td><td>ipr</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-22-2</td><td>You</td><td>H</td><td>H</td><td>CH₃</td><td>IP_r</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-22-3</td><td>You</td><td>H</td><td>H</td><td>CH(CH₃)₂</td><td>IP_r</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-22-4</td><td>You</td><td>H</td><td>H</td><td>CH₂CH(CH₃)₂</td><td>*Pr</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 11-22-5</td><td>You</td><td>H</td><td>H</td><td>CH₂Ph</td><td>*Pr</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-22-6</td><td>You</td><td>H</td><td>H</td><td>CH₂-indole-3-yl</td><td>*Pr</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-22-7</td><td>You</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td>^JP</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-22-8</td><td>You</td><td> *</td><td>H</td><td> *</td><td>^andP</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

*R² and R^3b linked together by (CH₂)₃ to form a ring of

127/967 five members.

Table 11-23.

<td>N^!</td><td>R¹</td><td>R²</td><td>R^3rd</td><td>R^3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>¹ R⁹</td>

<td>II-23-1</td><td>IP_r</td><td>H</td><td>H</td><td>H</td><td>³P</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-23-2</td><td>^andP</td><td>H</td><td>H</td><td>ch₃</td><td>ipr</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-23-3</td><td>IP_r</td><td>H</td><td>H</td><td>ch(ch₃)₂</td><td>^xP</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-23-4</td><td>³P</td><td>H</td><td>H</td><td>CH₂CH(CH₃)₂</td><td>IP_r</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>XI-23-5</td><td>IP_r</td><td>H</td><td>H</td><td>CH₂Ph</td><td>*Pr</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-23-6</td><td>^andP</td><td>H</td><td>H</td><td>CH₂-indole-3-</td><td>island³P</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-23-7</td><td>IP_r</td><td>H</td><td>H</td><td>Γ'ΊΙ Γ*·υ CfU L-í12 Γ12</td><td>IP_r</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-23-8</td><td>^andP</td><td> *</td><td>H</td><td> *</td><td>I?x*</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>*R² and R</td><td colspan="3">^3b linked</td><td>together for</td><td>(CH₂)₃</td><td colspan="4">to form</td><td colspan="2">ring</td><td>from</td>

five members.

Table 11-24.

<td>No</td><td>R¹</td><td>R²</td><td>R^3rd</td><td>RIB</td><td>_R4</td><td>R^yes</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>II-24-1</td><td>^cBoo</td><td>H</td><td>H</td><td>H</td><td>²P</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-24-2</td><td>^fcBoo</td><td>H</td><td>H</td><td>ch₃</td><td>^Pr</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-24-3</td><td>^cBoo</td><td>H</td><td>H</td><td>CH(CH₃)₂</td><td>³P</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-24-4</td><td>^cBoo</td><td>H</td><td>H</td><td>CH₂CH(CH₃)₂</td><td>ip_r</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-24-5</td><td>^fcBoo</td><td>H</td><td>H</td><td>CH₂Ph</td><td>'Pr</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-24 -6</td><td>^fcBoo</td><td>H</td><td>H</td><td>CH₂-indole-3-yl</td><td>¹P</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 11-24-7</td><td>^cBoo</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td>'Pr</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-24-8</td><td>^fcBoo</td><td> *</td><td>H</td><td> *</td><td>^andP</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

*R² and R^3b linked together by (CH₂)₃ to form a five-membered ring.

Table 11-25.

<td></td><td>R¹</td><td>R²</td><td>R^3rd</td><td>_R3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>II-25-1</td><td>Ph</td><td>The</td><td>The</td><td>The</td><td>IP_r</td><td>The</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>NH₂</td>

<td>II-25-2</td><td>Ph</td><td>The</td><td>The</td><td>ch₃</td><td>^JP</td><td>The</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-25-3</td><td>Ph</td><td>The</td><td>The</td><td>CH{CH₃)₂</td><td>IP_r</td><td>The</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

128/967

<td>No!</td><td>R¹</td><td>_r2</td><td>_R3rd</td><td>R^3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td> 11-25-4</td><td>Ph</td><td>H</td><td>H</td><td>CH₂CH(CH₃)₂</td><td>LP_r</td><td>H</td><td>CH₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-25-5</td><td>Ph</td><td>H</td><td>H</td><td>CH₂Ph</td><td>^andP</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-25-6</td><td>Ph</td><td>H</td><td>H</td><td>CH₂-indole-3</td><td>-ila⁷P</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-25-7</td><td>Ph</td><td>H</td><td>H</td><td></td><td>IP_r</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-25-8</td><td>Ph</td><td> *</td><td>H</td><td> *</td><td>and_for</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>*R² and R</td><td colspan="3">^3b linked</td><td>together for</td><td colspan="2">(CH₂) 3 for</td><td colspan="2">form</td><td>ring</td><td colspan="2">. of</td><td></td>

five members.

Table 11-26.

<td>N'</td><td>R¹</td><td>R²</td><td>R_3rd</td><td colspan="2">_R3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>_r8</td><td>R⁹</td>

<td>II-</td><td>p-Me-</td><td>The</td><td>The</td><td>The</td><td></td><td>*Pr</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 26-1</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>p-Me-</td><td>The</td><td>The</td><td>ch₃</td><td></td><td>⁷P</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 26-2</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>p-Me-</td><td>The</td><td>The</td><td>CH(CH₃)₂</td><td></td><td>^andP</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 26-3</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>p-Me-</td><td>The</td><td>The</td><td>CH₂CH(CH₃)</td><td> 2</td><td>¹ P</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 26-4</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>p-Me-</td><td>The</td><td>The</td><td>CH₂Ph</td><td></td><td>IP_r</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 26-5</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>p-Me-</td><td>The</td><td>The</td><td>CH₂-indole·</td><td> -3-</td><td>^JP</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 26-6</td><td>Ph</td><td></td><td></td><td>island</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>p-Me-</td><td>The</td><td>The</td><td>CH₂CH₂SCH₃</td><td></td><td>IP_r</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 26-7</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>p-Me-</td><td> *</td><td>The</td><td> ★</td><td></td><td>IP_r</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 26-8</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>*R² and</td><td colspan="2">R^3b linked</td><td colspan="2">together for</td><td>(CH₂)</td><td colspan="2">3 for</td><td colspan="2">form</td><td>ring</td><td>from</td><td></td><td></td>

<td>five</td><td colspan="2">members.</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td colspan="2">Table 11-27</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>No!</td><td>R¹</td><td>R²</td><td>R^3rd</td><td>R₃yes</td><td></td><td>r4</td><td>RS</td><td>R^yes</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

129/967

<td>N'</td><td>R¹</td><td>R²</td><td>_R3rd</td><td>R^3b</td><td>R⁴</td><td>R^yes</td><td>_r6</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>II-</td><td>pF-</td><td>H</td><td>H</td><td>H</td><td>'Pr</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 27-1</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II ~</td><td>pF-</td><td>H</td><td>H</td><td>ch₃</td><td>'Pr</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 27-2</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>pF-</td><td>H</td><td>H</td><td>ch(ch₃)₂</td><td>IP_r</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 27-3</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>pF-</td><td>H</td><td>H</td><td>CH₂CH (CH₃) 2</td><td>^andP</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 27-4</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>pF-</td><td>H</td><td>H</td><td>CH₂Ph</td><td>IP_r</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 27-5</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>pF-</td><td>H</td><td>H</td><td>CH₂-indole-3-</td><td>ipr</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 27-6</td><td>Ph</td><td></td><td></td><td>island</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>pF-</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td>ipr</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 27-7</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>pF-</td><td> *</td><td>H</td><td> *</td><td>'Pr</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 27-8</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>*R² and</td><td colspan="4">R^3b linked together by (CH₂)</td><td colspan="2">13 for</td><td colspan="2">form</td><td>ring</td><td>from</td><td></td><td></td>

<td>five</td><td>member</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td colspan="2">Table 11-28.</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td></td><td>R¹</td><td>R²</td><td>R^3rd</td><td>_R3b</td><td>_r4</td><td>j“^5</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>II-</td><td>p-Cl-</td><td>H</td><td>H</td><td>H</td><td>'Pr</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 28-1</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>p-Cl-</td><td>H</td><td>H</td><td>ch₃</td><td>'Pr</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 28-2</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II -</td><td>p-Cl-</td><td>H</td><td>H</td><td>ch(ch₃)₂</td><td>'Pr</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 28-3</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>p-Cl-</td><td>H</td><td>H</td><td>ch₂ch(ch₃) 2</td><td>'Pr</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 28-4</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>"II"</td><td>p-Cl-</td><td>H</td><td>H</td><td>CH₂Ph</td><td>ip_r</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

130/967

<td>No!</td><td>R¹</td><td>R²</td><td>R^3rd</td><td>R^3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td> ¥</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td> 28-5</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>p-Cl -</td><td>H</td><td>H</td><td>CH₂-indole-3-</td><td>ip_r</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 28-6</td><td>Ph</td><td></td><td></td><td>island</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II -</td><td>p-Cl-</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td>ipr</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 28-7</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>p-Cl-</td><td> *</td><td>H</td><td> *</td><td>'Pr</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 28-8</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>*R² and</td><td colspan="2">R^3b linked</td><td colspan="2">together by (CH₂)</td><td colspan="2">3 for</td><td colspan="2">form</td><td>ring</td><td>from</td><td></td><td></td>

five members.

Table 11-29.

<td></td><td>R¹</td><td>_r2</td><td>R^3rd</td><td>R^3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>II- 29-1</td><td>p-Br- Ph</td><td>H</td><td>H</td><td>H</td><td>'Pr</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II- 29-2</td><td>p-Br- Ph</td><td>H</td><td>H</td><td>ch₃</td><td>'Pr</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II- 29-3</td><td>p-Br- Ph</td><td>H</td><td>H</td><td>CH(CH₃)₂</td><td>and_P</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II- 29-4</td><td>p-Br- Ph</td><td>H</td><td>H</td><td>CH₂CH(CH₃)₂</td><td>'Pr</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II- 29-5</td><td>p-Br- Ph</td><td>H</td><td>H</td><td>CH₂Ph</td><td>IP_r</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II- 29-6</td><td>p-Br- Ph</td><td>H</td><td>H</td><td>CH₂-indole-3- island</td><td>'Pr</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II- 29-7</td><td>p-Br- Ph</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td>'Pr</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II- 29-8</td><td>p-Br- Ph</td><td> *</td><td>H</td><td> *</td><td>³P</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

*R² and R^3b linked together by (CH₂)₃ to form a five-membered ring.

131/967

Table 11-30.

<td>N'</td><td>R¹</td><td>R²</td><td></td><td>R⁴</td><td>_RYes</td><td>r6</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>II-</td><td>pI-</td><td>H</td><td>H H</td><td>^xP</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 30-1</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>pI-</td><td>H</td><td>H CH₃</td><td>*Pr</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 30-2</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>pI-</td><td>H</td><td>H CH(CH₃)₂</td><td>IP_r</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 30-3</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>pI-</td><td>H</td><td>H CH₂CH(CH₃)</td><td> 2 ²P</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 30-4</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>pI-</td><td>H</td><td>H CH₂Ph</td><td>^xP</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 30-5</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>pI-</td><td>H</td><td>H CHz-indole-</td><td> -3- ^xP</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 30-6</td><td>Ph</td><td></td><td>go there</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>pI-</td><td>H</td><td>H CH₂CH₂SCH₃</td><td>²P</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 30-7</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>pI-</td><td> *</td><td>H *</td><td>IP_r</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 30-8</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>*R² and</td><td colspan="3">R^3d linked together by</td><td colspan="2">(CH₂)₃ for</td><td colspan="2">form</td><td>ring</td><td>from</td><td></td><td></td>

<td>five</td><td colspan="2">members.</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td colspan="2">Table 11-31.</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>No</td><td>R¹ R</td><td> 2</td><td>R^3rd R^3b</td><td>R⁴</td><td>R⁵</td><td>R^yes</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td> 11-31-</td><td>ch₃</td><td>The</td><td>H</td><td>H</td><td>ⁿBoo</td><td>H</td><td>CH₃</td><td>oh</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 1</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td> 11-31-</td><td>ch₃</td><td>H</td><td>H</td><td>ch₃</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>oh</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 2</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td> 11-31-</td><td>ch₃</td><td>The</td><td>H</td><td>CH(CH₃)₂</td><td>ⁿBU</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 3</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td> 11-31-</td><td>ch₃</td><td>H</td><td>H</td><td>ch₂ch(ch₃)₂</td><td>Boo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

132/967

<td>No!</td><td>R¹</td><td>R²</td><td>_R3rd</td><td> R^3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td> 11-31-</td><td>ch₃</td><td>H</td><td>H</td><td>CH₂Ph</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 5</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td> 11-31-</td><td>ch₃</td><td>H</td><td>H</td><td>CH₂-indole-3-</td><td>Boo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 6</td><td></td><td></td><td></td><td>island</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td> 11-31-</td><td>ch₃</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td>Boo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 7</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td> 11-31-</td><td>ch₃</td><td> *</td><td>H</td><td> *</td><td>Boo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 8</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>*R² and</td><td colspan="3">R^3b linked</td><td>together by (CH₂)</td><td colspan="2">3 for</td><td colspan="2">form</td><td>ring</td><td>from</td><td></td><td></td>

five members.

Table 11-32.

<td>No</td><td>R¹</td><td>R²</td><td>R^3rd</td><td>_R3b</td><td colspan="2">R⁴</td><td>R⁵</td><td>r6</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>II-32-1</td><td>You</td><td>The</td><td>The</td><td>The</td><td></td><td>Boo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>NH₂</td>

<td>II-32-2</td><td>You</td><td>The</td><td>The</td><td>ch₃</td><td></td><td>Boo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-32-3</td><td>You</td><td>The</td><td>The</td><td>CH(CH₃)₂</td><td></td><td>Boo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-32-4</td><td>You</td><td>The</td><td>The</td><td>CH₂CH(CH₃)₂</td><td></td><td>Boo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-32-5</td><td>You</td><td>The</td><td>The</td><td>CH₂Ph</td><td></td><td>Boo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-32-6</td><td>You</td><td>The</td><td>The</td><td>CH₂-indole-3</td><td>-ila</td><td>"Buu"</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-32-7</td><td>You</td><td>The</td><td>The</td><td>CH₂CH₂SCH₃</td><td></td><td>Boo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 11-32-8</td><td>You</td><td> *</td><td>The</td><td> *</td><td></td><td>"Buu"</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td colspan="4">*R² and R^3b five members linked. Table 11-33.</td><td>together for</td><td>(CH₂)</td><td colspan="2">3 for</td><td colspan="2">form</td><td colspan="3">ring of</td><td></td>

<td>N'</td><td>R¹</td><td>R²</td><td>R^3rd</td><td>R^3b</td><td></td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td> 11-33- 1</td><td>¹P</td><td>The</td><td>The</td><td>H</td><td></td><td>Boo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 11-33- 2</td><td>ipr</td><td>The</td><td>The</td><td>ch₃</td><td></td><td>Boo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 11-33-</td><td>P</td><td>The</td><td>The</td><td>CH(CH₃)₂</td><td></td><td>Boo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

133/967

<td>N'</td><td>R¹</td><td>R²</td><td>R^3rd</td><td>R^3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td> 3</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td> 11-33-</td><td>P</td><td>H</td><td>H</td><td>CH₂CH(CH₃)₂</td><td>ⁿBoo</td><td>H</td><td>CH₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 4</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td> 11-33-</td><td>IP_r</td><td>H</td><td>H</td><td>CH₂Ph</td><td>Boo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 5</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td> 11-33-</td><td>'Pr</td><td>H</td><td>H</td><td>CH₂-indole-3-</td><td>Boo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 6</td><td></td><td></td><td></td><td>island</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td> 11-33-</td><td></td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td>Boo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 7</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td> 11-33-</td><td>'Pr</td><td> *</td><td>H</td><td> *</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 8</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>*R² and</td><td colspan="3">R^3b linked</td><td>together by (CH₂)</td><td colspan="2">3 for</td><td colspan="2">form</td><td>ring</td><td>from</td><td></td><td></td>

<td>five</td><td colspan="2">members.</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td colspan="3">Table 11-34.</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>N'</td><td>R¹</td><td>R²</td><td>R^3rd</td><td>_R3b</td><td>r4</td><td>R⁵</td><td>R^yes</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td> 11-34-</td><td>^cBoo</td><td>H</td><td>H</td><td>H</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 1</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td> 11-34-</td><td>^AndYour</td><td>H</td><td>H</td><td>ch₃</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 2</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td> 11-34-</td><td>^lBoo</td><td>H</td><td>H</td><td>CH(CH₃)₂</td><td>Boo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 3</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td> 11-34-</td><td>Boo</td><td>H</td><td>H</td><td>CH₂CH(CH₃)₂</td><td>Boo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 4</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td> 11-34-</td><td>^fcBU</td><td>H</td><td>H</td><td>CH₂Ph</td><td>Boo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 5</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td> 11-34-</td><td>^üBoo</td><td>H</td><td>H</td><td>CH₂-indole-3-</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 6</td><td></td><td></td><td></td><td>island</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td> 11-34-</td><td>^fcBoo</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

134/967

<td>No!</td><td>LU</td><td>_R3b</td><td>R⁴ R^yes R^yes X</td><td>YR⁷ R⁸ R⁹</td>

<td> 11-34-</td><td>^cBu*h</td><td> *</td><td>ⁿBu H CH₃ OH</td><td>OH Η H NH₂</td>

<td> 8</td><td></td><td></td><td></td><td></td>

<td>*R² and</td><td>R^3b linked</td><td>together for</td><td>(CH₂)₃ to form</td><td>ring of</td>

five members.

Table 11-35.

<td>WR¹ R² R^3rd R^3b</td><td></td><td>r4</td><td>R⁵</td><td>R^and</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>II-35-1 Ph H H H</td><td></td><td>ⁿBoo</td><td>H</td><td>CH₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-35-2 Ph Η H CH₃</td><td></td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-35-3 Ph Η H CH(CH₃)₂</td><td></td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-35-4 Ph Η H CH₂CH(CH₃)₂</td><td></td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-35-5 Ph Η H CH₂Ph</td><td></td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-35-6 Ph Η H CH₂-indole-3</td><td>- island</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-35-7 Ph Η H CH₂CH₂SCH₃</td><td></td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>11-35-8 Ph * H *</td><td></td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>*R² and R^3b linked together by five members. Table 11-36.</td><td>(CH₂)</td><td colspan="2">₃ for</td><td colspan="2">form</td><td colspan="2">year 1 of</td><td></td><td></td>

<td>L bt CIS (X Ptí</td><td></td><td>R⁴</td><td>R^yes</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>II- p-Me- Η Η H 36-1 Ph</td><td></td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II- p-Me- Η H CH₃36-2 Ph</td><td></td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II- p-Me- Η H CH(CH₃)₂36-3 Ph</td><td></td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II- p-Me- Η H CH₂CH(CH₃) 36-4 Ph</td><td> 2</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II- p-Me- Η H CH₂Ph 36-5 Ph</td><td></td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II- p-Me- Η H CH₂-indole</td><td> -3-</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

135/967

<td>N*</td><td>R¹</td><td>R²</td><td>j-)3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td> 36-6</td><td>Ph</td><td></td><td>island</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>p-Me-</td><td>H</td><td>H CH₂CH₂SCH₃</td><td>Boo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 36-7</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>p-Me-</td><td> *</td><td>H *</td><td>Boo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 36-8</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>*R² and</td><td colspan="2">R^3b linked</td><td>together for</td><td colspan="2">(CH₂) 3 for</td><td colspan="2">form</td><td>ring</td><td>from</td><td></td><td></td>

five members.

Table 11-37.

<td>No»</td><td>R¹</td><td>_r2</td><td>R^3rd</td><td>_R3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>II-</td><td>pF-</td><td>H</td><td>H</td><td>H</td><td>Boo</td><td>H</td><td>CH₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 37-1</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>pF-</td><td>H</td><td>H</td><td>CH₃</td><td>Boo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 37-2</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>PF-</td><td>H</td><td>H</td><td>CH(CH₃)₂</td><td>Boo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 37-3</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>pF-</td><td>H</td><td>H</td><td>CH₂CH(CH₃)₂</td><td>Boo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 37-4</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>pF-</td><td>H</td><td>H</td><td>CH₂Ph</td><td>Boo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 37-5</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>pF-</td><td>H</td><td>H</td><td>CH₂-indole-3-</td><td>Boo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 37-6</td><td>Ph</td><td></td><td></td><td>island</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>PF-</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td>Boo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 37-7</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>pF-</td><td> *</td><td>H</td><td> *</td><td>Boo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 37-8</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>*R² and</td><td colspan="4">R^3b linked together by (CH₂)</td><td colspan="2">3 for</td><td colspan="2">to form</td><td>ring</td><td>from</td><td></td><td></td>

<td>five</td><td colspan="2">members.</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td colspan="2">Table U-38.</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>No!</td><td>R¹</td><td>R²</td><td>R^3rd</td><td>R^3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

136/967

<td>N'</td><td>R¹</td><td>_r2</td><td>R^3rd</td><td>_R3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>II-</td><td>p-Cl-</td><td>H</td><td>H</td><td>H</td><td>ⁿBoo</td><td>H</td><td>CH₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 38-1</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>p-Cl-</td><td>H</td><td>H</td><td>ch₃</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 38-2</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>p-Cl-</td><td>H</td><td>H</td><td>CH(CH₃) 2</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 38-3</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>p-ci-</td><td>H</td><td>H</td><td>CH₂CH(CH₃)</td><td> 2 ⁿBoo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 38-4</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>p-Cl-</td><td>H</td><td>H</td><td>CH₂Ph</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 38-5</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>p-Cl-</td><td>H</td><td>H</td><td>CH₂ -indole</td><td>-3- Boo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 38-6</td><td>Ph</td><td></td><td></td><td>L. —L</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II -</td><td>p-Cl-</td><td>H</td><td>H</td><td>ch₂ch₂school₃</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 38-7</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>p-Cl-</td><td> *</td><td>H</td><td> *</td><td>^r'Bu</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 38-8</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>*R² and</td><td colspan="2">R^3b linked</td><td colspan="2">Together for</td><td colspan="2">(CH₂) 3 for</td><td colspan="2">form</td><td>ring</td><td>from</td><td></td><td></td>

<td>five</td><td colspan="2">members.</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td colspan="2">Table 11-39.</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>N'</td><td></td><td>R²</td><td>R^3rd</td><td>R^3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>II-</td><td>p-Br-</td><td>H</td><td>H</td><td>H</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 39-1</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>p-Br-</td><td>H</td><td>H</td><td>ch₃</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 39-2</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>p-Br-</td><td>H</td><td>H</td><td>CH(CH₃)₂</td><td>"Bu"</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 39-3</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>p-Br-</td><td>H</td><td>H</td><td>ch₂ch (CH₃)</td><td>2”Bu</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 39-4</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>p-Br-</td><td>H</td><td>H</td><td>CH₂Ph</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

137/967

<td>No</td><td>R¹</td><td>R²</td><td>R^3rd</td><td>R^3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td> 39-5</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>p-Br-</td><td>H</td><td>H</td><td>CH₂-indole-3-</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 39-6</td><td>Ph</td><td></td><td></td><td>island</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>p-Br-</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 39-7</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>p-Br-</td><td> *</td><td>H</td><td> *</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 39-8</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>*R² and</td><td colspan="2">R^3b linked</td><td colspan="2">together by (CH₂)</td><td colspan="2">3 for</td><td colspan="2">form</td><td>ring</td><td>from</td><td></td><td></td>

five members.

Table 11-40.

<td>N·</td><td>R¹</td><td>R²</td><td>R^3rd</td><td>_R3b</td><td>jj 4</td><td>R^yes</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>II- 40-1</td><td>pI- Ph</td><td>H</td><td>H</td><td>H</td><td>ⁿBoo</td><td>H</td><td>CH₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II- 40-2</td><td>pI- Ph</td><td>H</td><td>H</td><td>ch₃</td><td>Boo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II- 40-3</td><td>pI- Ph</td><td>H</td><td>H</td><td>ch(ch₃)₂</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II- 40-4</td><td>pI- Ph</td><td>H</td><td>H</td><td>CH₂CH(CH₃)₂</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II- 40-5</td><td>pI- Ph</td><td>H</td><td>H</td><td>CH₂Ph</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II- 40-6</td><td>pI- Ph</td><td>H</td><td>H</td><td>CH₂-indole-3yl</td><td>Boo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II - 40-7</td><td>pI- Ph</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II- 40-8</td><td>pI- Ph</td><td> *</td><td>H</td><td> *</td><td>Boo</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

*R² and R^3b linked together by (CH₂)₃ to form a five-membered ring.

138/967

Table 1 to 11-41.

<td>N'</td><td>R¹</td><td>R²</td><td>_r3=</td><td>¹ R^3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>II-41-1</td><td>ch₃</td><td>H</td><td>H</td><td>H</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-41-2</td><td>ch₃</td><td>H</td><td>H</td><td>ch₃</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 11-41-3</td><td>ch₃</td><td>H</td><td>H</td><td>CH (CH₃) ₂</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>IX-41-4</td><td>ch₃</td><td>H</td><td>H</td><td>CH₂CH(CH₃)₂</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-41-5</td><td>ch₃</td><td>H</td><td>H</td><td>CH₂Ph</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 11-41-6</td><td>ch₃</td><td>H</td><td>H</td><td>CH₂-indole-3</td><td>-ila Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-41-7</td><td>ch₃</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-41-8</td><td>ch₃</td><td> *</td><td>H</td><td> *</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>*R² and R'</td><td colspan="3">^3b linked</td><td>together for</td><td colspan="2">(CH₂)₃ for</td><td colspan="2">form</td><td colspan="3">ring of</td><td></td>

five members.

Table 11-42.

<td>No</td><td>R¹</td><td>_r2</td><td>R^3rd</td><td>R^3b</td><td>R⁴</td><td>R⁵</td><td>R^and</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>II-42-1</td><td>You</td><td>H</td><td>H</td><td>H</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 11-42-2</td><td>You</td><td>H</td><td>H</td><td>ch₃</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-4 2-3</td><td>You</td><td>H</td><td>H</td><td>CH(CH₃)₂</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-42-4</td><td>You</td><td>H</td><td>H</td><td>CH₂CH(CH₃)₂</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-42-5</td><td>You</td><td>H</td><td>H</td><td>CH₂Ph</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 11-42-6</td><td>You</td><td>H</td><td>H</td><td>CH₂-indole-3-yl</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-42-7</td><td>You</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-42-8</td><td>You</td><td> *</td><td>H</td><td> *</td><td>Bz</td><td>The</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>*R² and R·</td><td colspan="3">^3b linked</td><td>together by (CH₂)</td><td colspan="2"> 1₃ for</td><td colspan="2">form</td><td colspan="2">ring</td><td>from</td><td></td>

five members.

<td colspan="13">Table 11-43.</td>

<td></td><td>R¹</td><td>R²</td><td>R^3rd</td><td>_R3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>II-43-1</td><td>Tr</td><td>H</td><td>H</td><td>H</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>NH₂</td>

<td>II-43-2</td><td>⁷P</td><td>H</td><td>H</td><td>CH₃</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-43-3</td><td>³P</td><td>H</td><td>H</td><td>CH(CH₃)₂</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-43-S</td><td>ip_r</td><td>H</td><td>H</td><td>CH₂EH(CH₃)₂</td><td>BZ</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

139/967

<td> 11-43-6 ^;</td><td>'Pr H</td><td>H</td><td>CH₂-indole-3-yl</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II -43-7</td><td>'Pr H</td><td>H</td><td>CH₂CH₂SCH₃</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-43-8^:</td><td>'Pr *</td><td>H</td><td> *</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>*R² and R^3b</td><td colspan="2">linked</td><td>together by (CH₂)</td><td colspan="2">3 for</td><td colspan="2">form</td><td colspan="2">ring</td><td>from</td><td></td>

five members.

Table 11-44.

<td>No!</td><td>R¹</td><td>R²</td><td>r3c</td><td>¹ R^3b</td><td>R⁴</td><td>R^yes</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td> 11-44-1</td><td>'Bu</td><td>H</td><td>H</td><td>H</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-44-2</td><td>^cBoo</td><td>H</td><td>H</td><td>ch₃</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-44-3</td><td>^fcBoo</td><td>H</td><td>H</td><td>CH(CH₃)₂</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-44-4</td><td>^cBoo</td><td>H</td><td>H</td><td>CH₂CH(CH₃)₂</td><td>BZ</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-44-5</td><td>^fcBoo</td><td>H</td><td>H</td><td>CH₂Ph</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-44 -6</td><td>^fcBoo</td><td>H</td><td>H</td><td>CH₂-indole-3-yl</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 11 - 4 4 - 7</td><td>^cBoo</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-44-8</td><td>^cBoo</td><td> *</td><td>H</td><td> *</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>*R² and R-</td><td colspan="3">^3b linked</td><td>together by (CH₂)</td><td colspan="2">3 for</td><td colspan="2">form</td><td colspan="3">ring of</td><td></td>

five members.

Table 11-45.

<td>No</td><td>R¹</td><td>R²</td><td>R^3rd</td><td>_R3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>II-45-1</td><td>Ph</td><td>H</td><td>H</td><td>H</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-45-2</td><td>Ph</td><td>H</td><td>H</td><td>ch₃</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 11-45-3</td><td>Ph</td><td>H</td><td>H</td><td>CH(CH₃)₂</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-45-4</td><td>Ph</td><td>H</td><td>H</td><td>ch₂ch(ch₃)₂</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>H-45-5</td><td>Ph</td><td>H</td><td>H</td><td>CH₂Ph</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-45-6</td><td>Ph</td><td>H</td><td>H</td><td>CH₂-indole-3-yl</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-45-7</td><td>Ph</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II-45-8</td><td>Ph</td><td> ★</td><td>H</td><td> *</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

*R² and R^3b linked together by (CH₂)₃ to form a five-membered ring.

Table 11-46.

140/967

<td>N'</td><td>R¹</td><td>R²</td><td>R^3rd</td><td>_R3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>II-</td><td>p-Me-</td><td>H</td><td>H</td><td>H</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>NH₂</td>

<td> 46-1</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>p-Me-</td><td>H</td><td>H</td><td>ch₃</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 46-2</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II -</td><td>p-Me-</td><td>H</td><td>H</td><td>CH(CH₃)₂</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 46-3</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>p-Me-</td><td>H</td><td>H</td><td>CH₂CH(CH₃)₂</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 46-4</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>p-Me-</td><td>H</td><td>H</td><td>CH₂Ph</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 46-5</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>p-Me-</td><td>H</td><td>H</td><td>CH₂-indole-3-</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 46-6</td><td>Ph</td><td></td><td></td><td>island</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>p-Me-</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 46-7</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>p-Me-</td><td> *</td><td>H</td><td> *</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 46-8</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>*R² and</td><td colspan="2">R^3b linked</td><td colspan="2">together by (CH₂)</td><td colspan="2">3 for</td><td colspan="2">form</td><td>ring</td><td>from</td><td></td><td></td>

<td>five</td><td colspan="2">members.</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td colspan="2">Table 11-47.</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>N'</td><td>R¹</td><td>R²</td><td>R^3rd</td><td>R^3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td> 11-47-</td><td>pF-</td><td>H</td><td>H</td><td>H</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 1</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td> 11-47-</td><td>PF-</td><td>H</td><td>H</td><td>ch₃</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 2</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td> 11-47-</td><td>pF-</td><td>H</td><td>H</td><td>CH(CH₃)₂</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 3</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>XI - 4 7 -</td><td>pF-</td><td>H</td><td>H</td><td>CH₂CH(CH₃) 2</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 4</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td> 11-47-</td><td>pF-</td><td>H</td><td>H</td><td>CH₂Ph</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

141/967

<td></td><td>R¹</td><td>R²</td><td>_R3rd</td><td>R^3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td> 5</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td> 11-47-</td><td>pF-</td><td>H</td><td>H</td><td>CH₂-indole-3-</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>NH₂</td>

<td> 6</td><td>Ph</td><td></td><td></td><td>x the</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td> 11-47-</td><td>pF-</td><td>H</td><td>H</td><td>ch₂ch₂school₃</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 7</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td> 11-47-</td><td>pF-</td><td> *</td><td>H</td><td> *</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 8</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>*R² and</td><td colspan="2">R^3b linked</td><td colspan="2">together by (CH₂)</td><td colspan="2">¹₃ for</td><td colspan="2">form</td><td>ring</td><td>from</td><td></td><td></td>

five members.

Table 11-48.

<td>No</td><td>R¹</td><td>R²</td><td>R^3rd</td><td>R^3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>II- 48-1</td><td>p-Cl- Ph</td><td>The</td><td>H</td><td>H</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II- 48-2</td><td>p-Cl- Ph</td><td>H</td><td>H</td><td>ch₃</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II- 48-3</td><td>p-Cl- Ph</td><td>H</td><td>H</td><td>CH(CH₃)₂</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II- 48-4</td><td>p-Cl- Ph</td><td>H</td><td>H</td><td>CH₂CH(CH₃)₂</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II- 48-5</td><td>p-Cl- Ph</td><td>H</td><td>H</td><td>CH₂Ph</td><td>B z</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II- 48-6</td><td>p-Cl- Ph</td><td>H</td><td>H</td><td>CH₂-indole-3yl</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II- 48-7</td><td>p-Cl- Ph</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>II- 48-8</td><td>p-Cl- Ph</td><td> *</td><td>H</td><td> *</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

*R² and R^3b linked together by (CH₂)₃ to form a five-membered ring.

142/967

Table 11-49.

<td>N'</td><td>R¹</td><td>R²</td><td>R^3rd</td><td>_R3b</td><td>R⁴</td><td>_Ryes</td><td>R^and</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>II-</td><td>p-Br-</td><td>H</td><td>H</td><td>H</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>NH₂</td>

<td> 49-1</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II -</td><td>p-Br-</td><td>H</td><td>H</td><td>ch₃</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 49-2</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>p-Br-</td><td>H</td><td>H</td><td>CH(CH₃) ₂</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 49-3</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>p-Br-</td><td>H</td><td>H</td><td>CH₂CH(CH₃)₂</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 49-4</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>p-Br-</td><td>H</td><td>H</td><td>CH₂Ph</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 4 9-5</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>p-Br-</td><td>H</td><td>H</td><td>CH₂-indole-3-</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 49-6</td><td>Ph</td><td></td><td></td><td>ΐ 1 gL</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>p-Br-</td><td>H</td><td>H</td><td>ch₂ch₂school₃</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 49-7</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>II-</td><td>p-Br-</td><td> *</td><td>H</td><td> *</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 49-8</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>*R² and</td><td colspan="2">R^3b linked</td><td colspan="2">together by (CH₂)</td><td colspan="2">3 for</td><td colspan="2">form</td><td>ring</td><td>from</td><td></td><td></td>

<td>five</td><td colspan="2">members.</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td colspan="2">Table 11-50.</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>N'</td><td>R¹</td><td>R²</td><td>R^3rd</td><td>R^3b</td><td>R⁴</td><td>R^yes</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td> 11-50-</td><td>pI-</td><td>H</td><td>H</td><td>H</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 1</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td> 11-50-</td><td>pI-</td><td>H</td><td>H</td><td>CH₃</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 2</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td> 11-50-</td><td>pI-</td><td>H</td><td>H</td><td>CH (CH₃) 2</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 3</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td> 11-50-</td><td>pI-</td><td>H</td><td>H</td><td>CH₂CHÍCH₃)₂</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 4</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

143/967

<td></td><td>N'</td><td>R¹</td><td>R²</td><td>R^3rd</td><td colspan="2">_R3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td> -</td><td> 11-50-</td><td>pI-</td><td>H</td><td>H</td><td>CH₂Ph</td><td></td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td></td><td> 5</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td></td><td> 11-50-</td><td>pI-</td><td>H</td><td>H</td><td>CHj-indole-</td><td> -3-</td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>NHZ</td>

<td></td><td> 6</td><td>Ph</td><td></td><td></td><td>island</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td></td><td> 11-50-</td><td>pI-</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td></td><td>BZ</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td></td><td> 7</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td></td><td> 11-50-</td><td>pI-</td><td> *</td><td>H</td><td> *</td><td></td><td>Bz</td><td>H</td><td>ch₃</td><td>OH</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td></td><td> 8</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td></td><td>*R² and</td><td colspan="2">R^3b linked</td><td colspan="2">together for</td><td>(CH₂)</td><td colspan="2">3 for</td><td colspan="2">form</td><td>ring</td><td>from</td><td></td><td></td>

<img file="BRPI0809654A2_D0016.tif" />

<td>Table</td><td colspan="3">III-l.</td><td colspan="9">III</td>

<td>No</td><td>R¹</td><td>R²</td><td>R^3rd</td><td>_R3b</td><td>R⁴</td><td>R^yes</td><td>R⁶</td><td>X</td><td>And</td><td>_r7</td><td>R⁸</td><td>R⁹</td>

<td>III-ll</td><td>ch₃</td><td>H</td><td>H</td><td>H</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>NH₂</td>

<td>III-1-2</td><td>ch₃</td><td>H</td><td>H</td><td>ch₃</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-1-3</td><td>ch₃</td><td>H</td><td>H</td><td>CH(CH₃)₂</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-1-4</td><td>ch₃</td><td>H</td><td>H</td><td>CH₂CH(CH₃)₂</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-1-5</td><td>ch₃</td><td>H</td><td>H</td><td>CH₂Ph</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-1-6</td><td>CH₃</td><td>H</td><td>H</td><td>CH₂-indole-3-yl</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-1-7</td><td>ch₃</td><td>H</td><td>H</td><td>ch₂ch₂school₃</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-1-8</td><td>ch₃</td><td> *</td><td>H</td><td> *</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

144/967 *R² and R^3b linked together by (CH₂)₃ to form a five-membered ring.

Table III-2.

<td>N^!</td><td>R¹</td><td>_R2</td><td>R^3rd</td><td>R^3b</td><td>R⁴</td><td>R^yes</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>III-2-1</td><td>You</td><td>H</td><td>H</td><td>H</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>NH₂</td>

<td>III-2-2</td><td>You</td><td>H</td><td>H</td><td>ch₃</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-2-3</td><td>You</td><td>H</td><td>H</td><td>CH(CH₃) ₂</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-2-4</td><td>You</td><td>H</td><td>H</td><td>CH₂CH(CH₃)₂</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-2-5</td><td>You</td><td>H</td><td>H</td><td>CH₂Ph</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-2-6</td><td>You</td><td>H</td><td>H</td><td>CH₂-indole-3-yl</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-2-7</td><td>You</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-2-8</td><td>You</td><td> *</td><td>H</td><td> *</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>*R² and R</td><td colspan="3">^3b linked</td><td>together by (CH₂)</td><td colspan="2">3 for</td><td colspan="2">form</td><td colspan="2">ring</td><td>from</td><td></td>

five members.

Table III-3.

<td></td><td>R¹</td><td>R²</td><td>R^3rd</td><td>' R^3b</td><td colspan="2">R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>III-3-1</td><td>IP_r</td><td>H</td><td>H</td><td>H</td><td></td><td>ch₃</td><td>H</td><td>CH₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-3-2</td><td>P</td><td>H</td><td>H</td><td>ch₃</td><td></td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 111-3-3</td><td>*Pr</td><td>H</td><td>H</td><td>ch(ch₃)₂</td><td></td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-3-4</td><td>³P</td><td>H</td><td>H</td><td>CH₂CH(CH₃)₂</td><td></td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-3-5</td><td>^dP</td><td>H</td><td>H</td><td>CH₂Ph</td><td></td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-3-6</td><td>P</td><td>H</td><td>H</td><td>CH₂-indole-3</td><td>-ila</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-3-7</td><td>P</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td></td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-3-8</td><td>*Pr</td><td> *</td><td>H</td><td> *</td><td></td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td colspan="4">*R² and R^3b five members linked. Table III-4.</td><td>together for</td><td>(CH₂)</td><td colspan="2">3 for</td><td colspan="2">form</td><td colspan="2">ring</td><td>from</td><td></td>

<td>No!</td><td>R¹</td><td>R²</td><td>_R3rd</td><td>R^3b</td><td></td><td>R⁴</td><td>R⁵</td><td>R^yes</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>III-4-1</td><td>^cBoo</td><td>H</td><td>H</td><td>H</td><td></td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-4-2</td><td>^bBoo</td><td>H</td><td>H</td><td>ch₃</td><td></td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

145/967

<td>N*</td><td>R¹</td><td>R²</td><td>R^3rd</td><td>' R^3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R'</td><td>' R⁸</td><td>R⁹</td>

<td>III-4-3</td><td>^lBoo</td><td>H</td><td>H</td><td>CH(CH₃)₂</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-4-4</td><td>^üBoo</td><td>H</td><td>H</td><td>CH₂CH(CH₃)₂</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-4-5</td><td>^fcBoo</td><td>H</td><td>H</td><td>CH₂Ph</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 111-4-6</td><td>^cBoo</td><td>H</td><td>H</td><td>CH₂-indole-3-yl</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-4-7</td><td>^tBoo</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-4-8</td><td>^cBoo</td><td> *</td><td>H</td><td> *</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>*R² and R^:</td><td colspan="3">^3b linked</td><td>together by (CH₂)</td><td colspan="2">₃ for</td><td colspan="2">form</td><td colspan="2">ring</td><td>from</td><td></td>

five members.

Table III-5.

<td>No!</td><td>R¹ R²</td><td>R^3rd</td><td colspan="2">_R3b</td><td>R⁴</td><td>R^yes</td><td>R^yes</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>III-5-1</td><td>Ph H</td><td>H</td><td>H</td><td></td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>ΣΙΙ-5-2</td><td>Ph H</td><td>H</td><td>ch₃</td><td></td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-5-3</td><td>Ph H</td><td>H</td><td>CH(CH₃)₂</td><td></td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-5-4</td><td>Ph H</td><td>H</td><td>CH₂CH(CH₃) ₂</td><td></td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 111-5-5</td><td>Ph H</td><td>H</td><td>CH₂Ph</td><td></td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-5-6</td><td>Ph H</td><td>H</td><td>CH₂-indole-3-</td><td>island</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>IIX-5-7</td><td>Ph H</td><td>H</td><td>CH₂CH₂SCH₃</td><td></td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-5-8</td><td>Ph *</td><td>H</td><td> *</td><td></td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>*R² and R</td><td colspan="2">^3b linked</td><td>together for.</td><td>ICH₂)</td><td colspan="2">13 for</td><td colspan="2">form</td><td colspan="3">ring of</td><td></td>

<td colspan="2">five members</td><td> •</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>Table</td><td>III-6.</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>N'</td><td>R¹</td><td>R²</td><td>R^3rd R³^</td><td></td><td>R⁴</td><td>R^yes</td><td>and_r6</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>III-6-</td><td>p-Me-</td><td>H</td><td>H H</td><td></td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 1</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-6-</td><td>p-Me-</td><td>H</td><td>H CH₃</td><td></td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 2</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-6-</td><td>p-Me-</td><td>H</td><td>H CH(CH₃)₂</td><td></td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 3</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-6-</td><td>p-Me-</td><td>H</td><td>H CH₂CH(CH₃)</td><td> 2</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

146/967

<td>N^!</td><td>R¹</td><td>R²</td><td>_R3rd</td><td>R^3b</td><td>R⁴</td><td>r^£</td><td>' R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>_R9</td>

<td> 4</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-6-</td><td>p-Me-</td><td>H</td><td>H</td><td>CH₂Ph</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 5</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-6-</td><td>p-Me-</td><td>H</td><td>H</td><td>CH₂-indole-3-</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 6</td><td>Ph</td><td></td><td></td><td>island</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-6-</td><td>p-Me-</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 7</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-6-</td><td>p-Me-</td><td> *</td><td>H</td><td> *</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 8</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>*R² and</td><td colspan="2">R^3b linked</td><td colspan="2">together by (CH₂)</td><td colspan="2">3 for</td><td colspan="2">form</td><td>ring</td><td>from</td><td></td><td></td>

five members.

Table III-7.

<td></td><td>R¹</td><td>R²</td><td>_R3rd</td><td>R_3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>III-7- 1</td><td>pF- Ph</td><td>H</td><td>H</td><td>H</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-7- 2</td><td>pF- Ph</td><td>H</td><td>H</td><td>CH₃</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-7- 3</td><td>pF- Ph</td><td>H</td><td>H</td><td>CH(CH₃) ₂</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-7- 4</td><td>pF- Ph</td><td>H</td><td>H</td><td>CH₂CH(CH₃)₂</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-7- 6</td><td>pF- Ph</td><td>H</td><td>H</td><td>CH₂Ph</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-7- 7</td><td>pF- Ph</td><td>H</td><td>H</td><td>CH₂-indole-3- island</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-7- 8</td><td>PF- Ph</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-7- 20</td><td>pF- Ph</td><td> *</td><td>H</td><td> *</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

147/967 *R² and R^3b linked together by (CH₂)₃ to form a five-membered ring.

Table III-8.

<td></td><td>R¹</td><td>R²</td><td>R^3rd</td><td>_R3b</td><td>R⁴</td><td>rS</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>III-8-</td><td>p-Cl-</td><td>H</td><td>H</td><td>H</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>NH₂</td>

<td>1 III-8-</td><td>Ph p-Cl-</td><td>H</td><td>H</td><td>ch₃</td><td>CH₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>2 III-8-</td><td>Ph p-Cl-</td><td>H</td><td>H</td><td>CH{CH₃)₂</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>3 UI-8-</td><td>Ph p-Cl-</td><td>H</td><td>H</td><td>CH₂CH(CH₃)₂</td><td>ch₃</td><td>H</td><td>CH 3</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>4 III-8-</td><td>Ph p-Cl-</td><td>H</td><td>H</td><td>CH₂Ph</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>5 III-8-</td><td>Ph p-Cl-</td><td>H</td><td>H</td><td>CH₂-indole-3-</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>6 UI-8-</td><td>Ph p-Cl-</td><td>H</td><td>H</td><td>island k_.Fl 2 ^112 O ^-113</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 7 111-8-</td><td>Ph p-Cl-</td><td> *</td><td>H</td><td> *</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

Ph *R² and R^3b linked together by (CH₂)₃ to form a five-membered S ring.

Table UI-9.

<td>No</td><td>Laugh</td><td>_r2</td><td>R^3rd</td><td>_R3b</td><td>R⁴</td><td>R^yes</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>III-9-</td><td>p-Br-</td><td>H</td><td>H</td><td>H</td><td>CH₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>NH₂</td>

<td> 1</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>UI-9-</td><td>p-Br-</td><td>H</td><td>H</td><td>ch₃</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 2</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-9-</td><td>p-Br-</td><td>H</td><td>H</td><td>ch(ch₃)₂</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

Ph

148/967

<td>No!</td><td>R¹</td><td>R²</td><td>R^3rd</td><td>_R3b</td><td>R⁴</td><td>R⁵</td><td>¹ R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>_R9</td>

<td>III-9-</td><td>p-Br-</td><td>H</td><td>H</td><td>CH₂CH(CH₃)₂</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 4</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-9-</td><td>p-Br-</td><td>H</td><td>H</td><td>CH₂Ph</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 6</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-9-</td><td>p-Br-</td><td>H</td><td>H</td><td>CH₂-indole-3-</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 7</td><td>Ph</td><td></td><td></td><td>island</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-9-</td><td>p-Br-</td><td>H</td><td>H</td><td>ch₂ch₂school₃</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 8</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-9-</td><td>p-Br-</td><td> *</td><td>H</td><td> *</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 20</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>*R² and</td><td colspan="2">R^3b linked</td><td colspan="2">together by (CH₂)₃</td><td colspan="2">for</td><td colspan="2">form</td><td>ring</td><td>from</td><td></td><td></td>

five members.

Table III-10.

<td>N^!</td><td>R¹</td><td>_r2</td><td>R^3rd</td><td>R^3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>III- 10-1</td><td>pI- Ph</td><td>H</td><td>H</td><td>H</td><td>CH₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III- 10-2</td><td>pI- Ph</td><td>H</td><td>H</td><td>ch₃</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III- 10-3</td><td>pI- Ph</td><td>H</td><td>H</td><td>CH(CH₃)₂</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III- 10-4</td><td>pI- Ph</td><td>H</td><td>H</td><td>CH₂CH(CH₃)₂</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III- 10-5</td><td>pI- Ph</td><td>H</td><td>H</td><td>CH₂Ph</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III- 10-6</td><td>pI- Ph</td><td>H</td><td>H</td><td>CH₂-indole-3yl</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III- 10-7</td><td>pi- Ph</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-</td><td>pI-</td><td> *</td><td>H</td><td> *</td><td>ch₃</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

149/967

<td>N*</td><td>R¹</td><td>R²</td><td>R³^ R^3b</td><td>R⁴</td><td>r^!</td><td> 3 _r6</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td> 10-8</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td colspan="4">*R² and R^3b linked together by (CH₂)₃five members. Table III-ll.</td><td colspan="2">for</td><td colspan="2">form</td><td>ring</td><td colspan="2">. of</td><td></td>

<td>No</td><td>R¹</td><td>_r2</td><td>R^3rd R^3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>_r8</td><td>R⁹</td>

<td>III-ll-l</td><td>ch₃</td><td>H</td><td>H H</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-11-2</td><td>ch₃</td><td>H</td><td>H CH₃</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-11-3</td><td>ch₃</td><td>H</td><td>H CH(CH₃)₂</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-11-4</td><td>ch₃</td><td>H</td><td>H CH₂CH(CH₃)₂</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-11-5</td><td>ch₃</td><td>H</td><td>H CH₂Ph</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-11-6</td><td>ch₃</td><td>H</td><td>H CH₂-indole-3-yl</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-11-7</td><td>ch₃</td><td>H</td><td>H CH₂CH₂SCH₃</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-11-8</td><td>ch₃</td><td> *</td><td>H *</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>*R² and R^3t</td><td colspan="3">' linked together by (CH₂)₃</td><td colspan="2">for</td><td colspan="2">form</td><td>ring</td><td colspan="2">. of</td><td></td>

five members.

Table III-12.

<td>N'</td><td>R¹</td><td>R²</td><td>_R3rd_R3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>III-12-1</td><td>You</td><td>H</td><td>H.H.</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-12-2</td><td>You</td><td>H</td><td>H CH₃</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-12-3</td><td>You</td><td>H</td><td>H CH(CH₃)₂</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-12-4</td><td>You</td><td>H</td><td>H CH₂CH(CH₃)₂</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-12-5</td><td>You</td><td>H</td><td>H CH₂Ph</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-12-6</td><td>You</td><td>H</td><td>H CH₂-indole-3-yl</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-12-7</td><td>You</td><td>H</td><td>H CH₂CH₂SCH₃</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-12-8</td><td>You</td><td> *</td><td>H *</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td colspan="4">*R² and R^3b linked together by (CH₂) five members. Table III-13.</td><td colspan="2">3 for</td><td colspan="2">form</td><td colspan="2">ring</td><td>from</td><td></td>

<td>Neither</td><td>R¹</td><td>R²</td><td>_R3rd_R3b</td><td>R⁴</td><td>R⁵</td><td>_r6</td><td>X</td><td>And</td><td>R</td><td>⁷ R⁸</td><td>R⁹</td>

150/967

<td>N'</td><td>R¹</td><td>R²</td><td>R^3rd</td><td>_R3b</td><td>R⁴</td><td>R^yes</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>III-13-1</td><td>IP_r</td><td>H</td><td>H</td><td>H</td><td>You</td><td>H</td><td>CH₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-13-2</td><td>*Pr</td><td>H</td><td>H</td><td>ch₃</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-13-3</td><td>² P</td><td>H</td><td>H</td><td>CH(CH₃)₂</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-13-4</td><td>*p-y»</td><td>H</td><td>H</td><td>CH₂CH(CH₃)₂</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-13-5</td><td>²P</td><td>H</td><td>H</td><td>CH₂Ph</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-13-6</td><td>IP_r</td><td>H</td><td>H</td><td>CH₂-indole-3-yl</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-13-7</td><td>^JP</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-13-8</td><td>ipr</td><td> *</td><td>H</td><td> *</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

*R² and R^3b linked together by (CH₂)₃ to form a five-membered ring.

Table III-14.

<td>No</td><td>R¹</td><td>R²</td><td>R 3rd</td><td>_R3b</td><td>R⁴</td><td>R^yes</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>III- 14-1</td><td>^CB you</td><td>H</td><td>H</td><td>H</td><td>And t</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III- 14-2</td><td>^fcB you</td><td>The</td><td>H</td><td>CH₃</td><td>And t</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III- 14-3</td><td>^CB you</td><td>H</td><td>H</td><td>CH(CH₃)₂</td><td>And t</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III- 14-4</td><td>^CB you</td><td>H</td><td>H</td><td>ch₂chick₃)₂</td><td>And t</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III- 14-5</td><td>^fcB you</td><td>H</td><td>H</td><td>CH₂Ph</td><td>And t</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III- 14-6</td><td>^CB you</td><td>H</td><td>H</td><td>CH₂-indole- 3 -row</td><td>And t</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III- 14-7</td><td>^CB you</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td>And t</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III- 14-8</td><td>^CB you</td><td> *</td><td>H</td><td> *</td><td>And t</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

151/967 *R² and R^3b linked together by (CH₂)₃ to form a five-membered ring.

Table III-15.

<td>N' R¹ R²</td><td colspan="2">_R3rd</td><td>_R3b</td><td>R⁴</td><td>R^yes</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>III-15-1 Ph H</td><td>H</td><td></td><td>H</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>NH₂</td>

<td>III-15-2 Ph H</td><td>H</td><td></td><td>ch₃</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-15-3 Ph H</td><td>H</td><td></td><td>CH(CH₃)₂</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-15-4 Ph H</td><td>H</td><td></td><td>CH₂CH(CH₃)₂</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-15-5 Ph H</td><td>H</td><td></td><td>CH₂Ph</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-15-6 Ph H</td><td>H</td><td></td><td>CH₂-indole-3-yl</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-15-7 Ph H</td><td>H</td><td></td><td>CH₂CH₂SCH₃</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>NH₂</td>

<td>III-15-8 Ph *</td><td>H</td><td></td><td> *</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>NH₂</td>

<td colspan="2">*R² and R^3b five members linked. Table III-16.</td><td colspan="2">together by (CH₂)</td><td colspan="2">3 for</td><td colspan="2">form</td><td colspan="3">ring of</td><td></td>

<td>N' R¹</td><td>R²</td><td>R^;</td><td>5th</td><td>R⁴</td><td>R^yes</td><td>r6</td><td>X</td><td>And</td><td>R⁷</td><td>R®</td><td>R⁹</td>

<td>III- p-Me- 16-1 Ph</td><td>H</td><td>H</td><td>H</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>NH₂</td>

<td>III- p-Me- 16-2 Ph</td><td>H</td><td>H</td><td>ch₃</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III- p-Me- 16-3 Ph</td><td>H</td><td>H</td><td>CH (CH₃) ₂</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III- p-Me- 16-4 Ph</td><td>H</td><td>H</td><td>CH₂CH(CH₃)₂</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>in- p-Me- 16-5 Ph</td><td>H</td><td>H</td><td>CH₂Ph</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III- p-Me- 16-6 Ph</td><td>H</td><td>H</td><td>CH₂-indole-3yl</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III- p-Me-</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

16-7 Ph

152/967

<td>N'</td><td>R¹</td><td>_r2</td><td>_R3rd</td><td>R^3b</td><td>R⁴</td><td>R^yes</td><td>' R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>III-</td><td>p-Me-</td><td> *</td><td>H</td><td> *</td><td>You</td><td>H</td><td>ch₃</td><td>p</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 16-8</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>*R² and R</td><td colspan="2">^3b linked</td><td colspan="2">together by (CH₂;</td><td colspan="2">13 for</td><td colspan="2">form</td><td>ring</td><td>from</td><td></td><td></td>

<td colspan="2">five members</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>Table</td><td>III-17</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>N'</td><td>R¹</td><td>R²</td><td>R^3rd</td><td>R^3b</td><td>R⁴</td><td>R^yes</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>III-17-</td><td>pF-</td><td>H</td><td>H</td><td>H</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 1</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-17-</td><td>pF-</td><td>H</td><td>H</td><td>ch₃</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 2</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-17-</td><td>PF-</td><td>H</td><td>H</td><td>CH(CHj)₂</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 3</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-17-</td><td>pF-</td><td>H</td><td>H</td><td>CH₂CH(CH₃) ₂</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 4</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>HI-17-</td><td>PF-</td><td>H</td><td>H</td><td>CH₂Ph</td><td>You</td><td>H</td><td>CH3</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 5</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-17-</td><td>pF-</td><td>H</td><td>H</td><td>CH₂ -indole- 3 -</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 6</td><td>Ph</td><td></td><td></td><td>island</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-17-</td><td>pF-</td><td>H</td><td>H</td><td>ch₂ch₂school₃</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 7</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-17-</td><td>pF-</td><td> *</td><td>H</td><td> ★</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 8</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>*R² and R</td><td colspan="2">^3b linked</td><td colspan="2">together by (CH₂)</td><td colspan="2">3 for</td><td colspan="2">form</td><td>ring</td><td>from</td><td></td><td></td>

<td colspan="2">five members.</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>Table</td><td>III-18.</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>No</td><td>R¹</td><td>R²</td><td>_R3rd</td><td></td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>III-</td><td>p-Cl-</td><td>H</td><td>H</td><td>H</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 18-1</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>P-Cl-</td><td>H</td><td>H</td><td>ch₃</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

153/967

<td>No!</td><td>R¹</td><td>R²</td><td>R^3rd</td><td>_R3b</td><td>R⁴</td><td>_Ryes</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td> 18-2</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>p-Cl-</td><td>H</td><td>H</td><td>CH(CH₃)₂</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 18-3</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>p-Cl-</td><td>H</td><td>H</td><td>CH₂CH(CH₃)₂</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 18-4</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>p-Cl-</td><td>H</td><td>H</td><td>CH₂Ph</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 18-5</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>p-Cl-</td><td>H</td><td>H</td><td>CH₂-indole-3-</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 18-6</td><td>Ph</td><td></td><td></td><td>island</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>p-Cl-</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 18-7</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>p-Cl-</td><td> ★</td><td>H</td><td> *</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 18-8</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>*R² and</td><td colspan="2">R^3b linked</td><td colspan="2">together by (CH₂)</td><td colspan="2"> 1₃ for</td><td colspan="2">form</td><td>ring</td><td>from</td><td></td><td></td>

<td>five</td><td>members.</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td colspan="2">Table UI-19.</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td></td><td>R¹</td><td>R²</td><td>_R3rd</td><td>_R3b</td><td>R⁴</td><td>R^yes</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>III-</td><td>p-Br-</td><td>H</td><td>H</td><td>H</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 19-1</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>p-Br-</td><td>H</td><td>H</td><td>ch₃</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 19-2</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III -</td><td>p-Br-</td><td>H</td><td>H</td><td>CH(CH₃)₂</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 19-3</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III -</td><td>p-Br-</td><td>H</td><td>H</td><td>ch₂ch(ch₃)₂</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 19-4</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>p-Br-</td><td>H</td><td>H</td><td>CH₂Ph</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 19-5</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>p-Br-</td><td>H</td><td>H</td><td>CH₂-indole-3-</td><td>You</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

19-6 Phila

154/967

<td> •</td>

<td>W KJ id u&gt; P&gt; id, tr id 4. id c XX id^ id CO id with</td>

<td>III- p-Br- Η H CH₂CH₂SCH₃ Et H CH₃ F OH Η H NH₂</td>

<td>19-7 Ph</td>

<td>III- p-Br- * H * Et H CH₃ F OH Η H NH₂</td>

<td>19-8 Ph</td>

<td>*R² and R^3b linked together by (CH₂)₃ to form a ring of</td>

<td>five members.</td>

<td>Table III-20.</td>

<td>N' R¹ R² R^3rd R^3b R⁴ R^yes R⁶ XYR⁷ R⁸ R⁹</td>

<td>III-20- pI- Η Η H Et H CH₃ F OH Η H NH₂</td>

<td>1 Ph</td>

<td>III-20- pI- Η H CH₃ Et H CH₃ F OH Η H NH₂</td>

<td>2 Ph</td>

<td>III-20- pI- Η H CH(CH₃)₂ Et H CH₃ F OH Η H NH₂</td>

<td>3 Ph</td>

<td>III-20- pI- Η H CH₂CH(CH₃)₂ Et H CH₃ F OH Η H NH₂</td>

<td>4 Ph</td>

<td>III-20- pI- Η H CH₂Ph Et H CH₃ F OH Η H NH₂</td>

<td>5 Ph</td>

<td>III-20- pI- Η H CH₂-indole-3- Et H CH₃ F OH Η H NH₂</td>

<td>6 Phila</td>

<td>III-20- pI- Η H CH₂CH₂SCH₃ Et H CH₃ F OH Η H NH₂</td>

<td>7 Ph</td>

<td>III-20- pI- * H * Et H CH₃ F OH Η H NH₂</td>

<td>8 Ph</td>

<td>*R² and R^3b linked together by (CH₂)₃ to form a ring of</td>

<td>5 five members.</td>

<td>Table III-21.</td>

<td>N! R¹ R² R^3rd R^3b R⁴ R⁵ R⁶ XYR⁷ R⁸ R⁹</td>

<td>III-21- CH₃ H H H³Pr H CH₃ F OH Η H NH₂</td>

155/967

<td>No.</td><td>R¹</td><td>R²</td><td>R^3rd R^3b</td><td>R⁴</td><td>R^:</td><td>¹ R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td> 1</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-21-</td><td>ch₃</td><td>H</td><td>H CH₃</td><td>and_for</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>NH₂</td>

<td> 2</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-21-</td><td>ch₃</td><td>H</td><td>H CH(CH₃)₂</td><td>^andP</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 3</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-21-</td><td>ch₃</td><td>H</td><td>H CH₂CH(CH₃)₂</td><td>*Pr</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 4</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>IXI-21-</td><td>ch₃</td><td>H</td><td>H CH₂Ph</td><td>IP_r</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 5</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-21-</td><td>ch₃</td><td>H</td><td>H CH₂-indole-3-</td><td>^JP</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 6</td><td></td><td></td><td>island</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-21-</td><td>ch₃</td><td>H</td><td>H CH₂CH₂SCH₃</td><td>IP_r</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 7</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-21-</td><td>ch₃</td><td> *</td><td>H *</td><td>^andP</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 8</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>*R² and R^3b</td><td colspan="3">linked together by (CH₂)₃</td><td colspan="2"></td><td colspan="2">form</td><td>ring</td><td>from</td><td></td><td></td>

five members.

Table ΣΙΙ-22.

<td>No!</td><td>R¹</td><td>R²</td><td>R^3rd</td><td>_R3b</td><td>R⁴</td><td>R⁵</td><td>R^yes</td><td>X</td><td>And</td><td>R⁷</td><td>_r8</td><td>R⁹</td>

<td>III-22-1</td><td>You</td><td>H</td><td>H</td><td>H</td><td>IP_r</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>NH₂</td>

<td>III-22-2</td><td>You</td><td>H</td><td>H</td><td>ch₃</td><td>^andP</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-22-3</td><td>You</td><td>H</td><td>H</td><td>CH(CH₃)₂</td><td>^toP</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-22-4</td><td>You</td><td>H</td><td>H</td><td>CH₂CH(CH₃)₂</td><td>IP_r</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-22-5</td><td>You</td><td>H</td><td>H</td><td>CH₂Ph</td><td>IP_r</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-22-6</td><td>You</td><td>H</td><td>H</td><td>CH₂-indole-3-yl</td><td>ip_r</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-22-7</td><td>You</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td>^andP</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-22-8</td><td>You</td><td> *</td><td>H</td><td> *</td><td>^andP</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

*R² and R^3b linked together by (CH₂)₃ to form 5 five-membered ring.

156/967

<td>N'</td><td>R¹</td><td>R²</td><td>_R3rd</td><td>_R3t&gt;</td><td>R⁴</td><td>R^yes</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R®</td><td>R⁹</td>

<td>III-23-</td><td>IP_r</td><td>H</td><td>H</td><td>H</td><td>^xP</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 1</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-23-</td><td>IP_r</td><td>H</td><td>H</td><td>ch₃</td><td>ipr</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 2</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-23-</td><td>ipr</td><td>H</td><td>H</td><td>CH(CH₃)₂</td><td>ipr</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 3</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-23-</td><td>IP_r</td><td>H</td><td>H</td><td>CH₂CH(CH₃)₂</td><td>ip_r</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 4</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-23-</td><td>'Pr</td><td>H</td><td>H</td><td>CH₂Ph</td><td>^xP</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 5</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-23-</td><td>³P</td><td>H</td><td>H</td><td>CH₂-indole-3-</td><td>³P</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 6</td><td></td><td></td><td></td><td>island</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-23-</td><td>IP_r</td><td>H</td><td>H</td><td>ch₂ch₂school₃</td><td>²P</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 7</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-23-</td><td>³ P</td><td> *</td><td>H</td><td> *</td><td>¹ P</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 8</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>*R² and R</td><td colspan="4">^3b linked together by (CH₂) ₃</td><td colspan="2">for</td><td colspan="2">form</td><td>ring</td><td>from</td><td></td><td></td>

<td colspan="3">five members.</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>Table</td><td colspan="2">III-24.</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>N'</td><td>R¹</td><td>R²</td><td>_R3rd</td><td>_R3b</td><td>R⁴</td><td>R^yes</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R®</td><td>_r9</td>

<td>III-24-</td><td>^cBoo</td><td>H</td><td>H</td><td>H</td><td>'Pr</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>NH₂</td>

<td> 1</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td> 111 - 2 4 -</td><td>^lBoo</td><td>H</td><td>H</td><td>ch₃</td><td>ipr</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 2</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-24-</td><td>^εBp</td><td>H</td><td>H</td><td>CH(CH₃)₂</td><td>IP_r</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 3</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-24-</td><td>^cBoo</td><td>H</td><td>H</td><td>CH₂CH(CH₃)₂</td><td>⁷P</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

157/967

<td>No!</td><td>R¹</td><td>R²</td><td>_R3rd_R3b</td><td>R⁴</td><td>R'</td><td>and_r6</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>III-24-</td><td>^cBoo</td><td>H</td><td>H CH₂Ph</td><td>IP_r</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 5</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-24-</td><td>^fBoo</td><td>H</td><td>H CH₂-indole-3-</td><td>IP_r</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 6</td><td></td><td></td><td>island</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-24-</td><td>^cBoo</td><td>H</td><td>H CH₂CH₂SCH₃</td><td>IP_r</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 7</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-24-</td><td>^fcBoo</td><td> ★</td><td>H *</td><td>⁷ P</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 8</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>*R² and R^3b</td><td colspan="3">linked together by (CH₂)</td><td colspan="2"> 1₃ for</td><td colspan="2">form</td><td>ring</td><td>from</td><td></td><td></td>

five members.

Table III-25.

<td>No</td><td>R¹</td><td>R²</td><td>_R3rd</td><td>R^3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>III-25-1</td><td>Ph</td><td>H</td><td>H</td><td>H</td><td>IP_r</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 111-25-2</td><td>Ph</td><td>H</td><td>H</td><td>ch₃</td><td>⁴ P</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>The</td><td>H</td><td>nh₂</td>

<td>III-25-3</td><td>Ph</td><td>H</td><td>H</td><td>CH(CH₃) ₂</td><td>IP_r</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 111-25-4</td><td>Ph</td><td>H</td><td>H</td><td>CH₂CH(CH₃)₂</td><td>ip_r</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-25-5</td><td>Ph</td><td>H</td><td>H</td><td>CH₂Ph</td><td>IP_r</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-25-6</td><td>Ph</td><td>H</td><td>H</td><td>CH₂-indole-3-yl</td><td>⁴ P</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-25-7</td><td>Ph</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td></td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-25-8</td><td>Ph</td><td> ★</td><td>H</td><td> *</td><td>²P</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

*R² and R^3b linked together by (CH₂)₃ to form a five-membered ring.

Table III-26.

<td>No</td><td>R¹</td><td>R²</td><td>_R3rd</td><td>_R3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>III-</td><td>p-Me-</td><td>H</td><td>H</td><td>H</td><td>⁴ P</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 26-1</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>p-Me-</td><td>H</td><td>H</td><td>ch₃</td><td>^xP</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 26-2</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>p-Me-</td><td>H</td><td>H</td><td>ch(ch₃)₂</td><td>ip_r</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

158/967

<td>N'</td><td>R¹</td><td>R²</td><td>R^3rd</td><td>_R3b</td><td>R⁴</td><td>R^yes</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td> 26-3</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>p-Me-</td><td>H</td><td>H</td><td>CH₂CH(CH₃) ₂</td><td>'Pr</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 26-4</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III -</td><td>p-Me-</td><td>H</td><td>H</td><td>CH₂Ph</td><td>'Pr</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 26-5</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>p-Me-</td><td>H</td><td>H</td><td>CH₂-indole-3-</td><td>'Pr</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 26-6</td><td>Ph</td><td></td><td></td><td>island</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>p-Me-</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td>IP_r</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 26-7</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>p-Me-</td><td> *</td><td>H</td><td> *</td><td>IP_r</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 26-8</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>*R² and</td><td colspan="2">R^3b linked</td><td colspan="2">together by (CH₂)₃</td><td colspan="2">for</td><td colspan="2">form</td><td>ring</td><td>from</td><td></td><td></td>

<td>five</td><td>members</td><td> •</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td colspan="2">Table III-27</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>N'</td><td>R¹</td><td>R²</td><td>R^3rd</td><td>R^3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>_r9</td>

<td>III-</td><td> 1</td><td>H</td><td>H</td><td>H</td><td>^andP</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 27-1</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>pF-</td><td>H</td><td>H</td><td>ch₃</td><td>P x*</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 27-2</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>pF-</td><td>H</td><td>H</td><td>CH(CH₃)₂</td><td>*Pr</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 27-3</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>pF-</td><td>H</td><td>H</td><td>ch₂ch(ch₃)₂</td><td>'Pr</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 27-4</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>pF-</td><td>H</td><td>H</td><td>CH₂Ph</td><td>²P</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 27-5</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>pF-</td><td>H</td><td>H</td><td>CH₂-indole-3-</td><td>IP_r</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 27-6</td><td>Ph</td><td></td><td></td><td>island</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>pF-</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td>⁴P</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

27-7 Ph

159/967

<td>No!</td><td>R¹</td><td>p2 R^3rd R^3b</td><td>W XJ σ\ X w CO w KO</td>

<td>III -</td><td>pF-</td><td>*H*</td><td>*Pr H CH₃ F OH H H NH₂</td>

<td> 27-8</td><td>Ph</td><td></td><td></td>

<td>*R² and</td><td colspan="2">R^3b linked together by</td><td>(CH₂)₃ to form a ring of</td>

five members.

Table III-28.

<td>No»</td><td>R¹</td><td>R²</td><td>R^3rd</td><td>R^3b</td><td>R⁴</td><td>R⁵</td><td>R^yes</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>III-</td><td>p-Cl-</td><td>H</td><td>H</td><td>H</td><td>'Pr</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 28-1</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>p-Cl-</td><td>H</td><td>H</td><td>CH₃</td><td>'Pr</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 28-2</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>p-Cl-</td><td>H</td><td>H</td><td>CH(CH₃)₂</td><td>⁴P</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 28-3</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>p-Cl-</td><td>H</td><td>H</td><td>CH₂CH(CH₃) 2</td><td>'Pr</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 28-4</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>p-ci-</td><td>H</td><td>H</td><td>CH₂Ph</td><td>'Pr</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 28-5</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>p-Cl-</td><td>H</td><td>H</td><td>CH₂-indole-3-</td><td>^andP</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 28-6</td><td>Ph</td><td></td><td></td><td>island</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>p-Cl -</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td>'Pr</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 28-7</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>p-Cl-</td><td> *</td><td>H</td><td> *</td><td>'Pr</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 28-8</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>*R² and</td><td colspan="2">R^3b linked</td><td colspan="2">together by (CH₂)₃</td><td colspan="2">for</td><td colspan="2">form</td><td>ring</td><td>from</td><td></td><td></td>

<td>five</td><td>members.</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td colspan="2">Table III-29.</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>N·</td><td>R¹</td><td>R²</td><td>_R3rd</td><td>R^3b</td><td>R⁴</td><td>R^yes</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>r9</td>

<td>III-</td><td>p-Br-</td><td>H</td><td>H</td><td>H</td><td>'Pr</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 29-1</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>p-Br-</td><td>H</td><td>H</td><td>CH₃</td><td>'Pr</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

160/967

<td>N'</td><td>R¹</td><td>R²</td><td>R^3rd</td><td>R3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td> 29-2</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>p-Br-</td><td>H</td><td>H</td><td>CH(CH₃)₂</td><td>⁷P</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 29-3</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>p-Br-</td><td>H</td><td>H</td><td>CH₂CH(CH₃)₂</td><td>^xP</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 29-4</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>p-Br-</td><td>H</td><td>H</td><td>CH₂Ph</td><td>ipr</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 29-5</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>p-Br-</td><td>H</td><td>H</td><td>CH₂-indole-3-</td><td>IP_r</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 29-6</td><td>Ph</td><td></td><td></td><td>island</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>p-Br-</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td>⁴P</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 29-7</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>p-Br-</td><td> *</td><td>H</td><td> *</td><td>³P</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 29-8</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>*R² and</td><td colspan="2">R^3b linked</td><td colspan="2">together by (CH₂)₃</td><td colspan="2">for</td><td colspan="2">form</td><td>ring</td><td>from</td><td></td><td></td>

<td>five</td><td>members</td><td> •</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td colspan="2">IU-30 table</td><td> .</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>N'</td><td>R¹</td><td>R²</td><td>R^3rd</td><td>R^3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>_r8</td><td>R⁹</td>

<td>III-</td><td>H</td><td>H</td><td>H</td><td>H</td><td>^xP</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 30-1</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>pi-</td><td>H</td><td>H</td><td>ch₃</td><td>^xP</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 30-2</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>pI-</td><td>H</td><td>H</td><td>CH(CH₃)₂</td><td>⁷P</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 30-3</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>pI-</td><td>H</td><td>H</td><td>CH₂CH(CH₃)₂</td><td>^xP</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 30-4</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>pI-</td><td>H</td><td>H</td><td>CH₂Ph</td><td>IP_r</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 30-5</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III -</td><td>pI-</td><td>H</td><td>H</td><td>CH₂ -indole-3 -</td><td>IP_r</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

30-6 Phila

161/967

<td> *</td>

<td>S 1 you w £ w cr tn ch X «I w</td>

<td>III- pI- Η H CH₂CH₂SCH₃⁴Pr H CH₃ F OH Η H NH₂</td>

<td>30-7 Ph</td>

<td>III- pI- * H *^xPr H CH₃ F OH Η H NH₂</td>

<td>30-8 Ph</td>

<td>*R² and R^3b linked together by (CH₂)₃ to form a ring of</td>

<td>five members.</td>

<td>Table III-31.</td>

<td>Ch What about Pá Pá įx x kO Pá Pá .r Shovel L Shovel &lt;0 Shovel CM Pa Pa s</td>

<td>III-31- CH₃ H H HⁿBu H CH₃ F OH Η H NH₂</td>

<td> 1</td>

<td>III-31- CH₃ H H CH₃ⁿBu H CH₃ F OH Η H NH₂</td>

<td> 2</td>

<td>_r III-31- CH₃ Η H CH(CH₃)₂ⁿBu H CH₃ F OH Η H NH₂</td>

<td> 3</td>

<td>III-31- CH₃ H H CH₂CH(CH₃)₂ⁿBu H CH₃ F OH Η H NH₂</td>

<td> 4</td>

<td>III-31- CH₃ H H CH₂PhⁿBu H CH₃ F OH Η H NH₂</td>

<td> 5</td>

<td>III-31- CH₃ H H CH₂-indole-3-ⁿBu H CH₃ F OH Η H NH₂</td>

<td>6 row</td>

<td>III-31- ch₃ η H CH₂CH₂SCH₃ Bu h ch₃ F OH hh nh₂</td>

<td> 7</td>

<td>III-31- CH₃ * H *ⁿBu H CH₃ F OH Η H NH₂</td>

and R^3b linked together by (CH₂)₃ to form 5 five-membered ring.

Table ΣΖΧ-32.

<td>N·</td><td>R¹</td><td>R²</td><td>R^3rd</td><td>_R3b</td><td>R⁴</td><td>R^yes</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>III-32-1</td><td>You</td><td>H</td><td>H</td><td>H</td><td>"Bu"</td><td>H</td><td>CH₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

162/967

<td>No.</td><td>R¹</td><td>R²</td><td>R^3rd R^3b</td><td>R⁴</td><td>R⁵</td><td>R^ê</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>_r9</td>

<td>III-32-2</td><td>You</td><td>H</td><td>H CH₃</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-32-3</td><td>You</td><td>H</td><td>H CH(CH₃)₂</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-32-4</td><td>You</td><td>H</td><td>H CH₂CH(CH₃)₂</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-32-5</td><td>You</td><td>H</td><td>H CH₂Ph</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-32-6</td><td>You</td><td>H</td><td>H CH₂-indole-3-yl</td><td>Boo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-32-7</td><td>You</td><td>H</td><td>H CH₂CH₂SCH₃</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-32-8</td><td>You</td><td> *</td><td>H *</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>*R² and R^3b</td><td colspan="3">linked together by (CH₂)</td><td colspan="2">3 for</td><td colspan="2">form</td><td colspan="3">sign of</td><td></td>

five members.

Table III-33.

<td>N'</td><td>R¹</td><td>R²</td><td>R^3rd</td><td>R₃b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>III-33- 1</td><td>³ P</td><td>H</td><td>H</td><td>H</td><td>ⁿBU</td><td>The</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>NH₂</td>

<td>III-33- 2</td><td>ipr</td><td>H</td><td>H</td><td>ch₃</td><td>ⁿBoo</td><td>The</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-33- 3</td><td>'Pr</td><td>H</td><td>H</td><td>CH(CH₃)₂</td><td>ⁿBoo</td><td>The</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-33- 4</td><td>IP_r</td><td>H</td><td>H</td><td>CH₂CH(CH₃)₂</td><td>ⁿBoo</td><td>The</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-33- 5</td><td>ip_r</td><td>H</td><td>H</td><td>CH₂Ph</td><td>ⁿBoo</td><td>The</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-33- 6</td><td>^xP</td><td>H</td><td>H</td><td>CH₂-indole-3- island</td><td>ⁿBoo</td><td>The</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-33- 7</td><td>^xP</td><td>H</td><td>H</td><td>ch₂ch₂school₃</td><td>Boo</td><td>The</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-33- 8</td><td>IP_r</td><td> *</td><td>H</td><td> *</td><td>ⁿBoo</td><td>The</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

*R² and R^3b linked together by (CH₂)₃ to form 5 five-membered ring.

163/967

Table III-34.

<td>No»</td><td>R¹</td><td>R²</td><td colspan="2">R^3rd R^3b</td><td>R⁴</td><td>R-</td><td>' R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>III-34-</td><td>^fcBoo</td><td>H</td><td>H</td><td>H</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 1</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-34-</td><td>^cBoo</td><td>H</td><td>H</td><td>ch₃</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 2</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-34-</td><td>^cBoo</td><td>H</td><td>H</td><td>CH(CH₃)₂</td><td>Boo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 3</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-34-</td><td>^fcBoo</td><td>H</td><td>H</td><td>CH₂CH(CH₃)₂</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 4</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-34-</td><td>^üBoo</td><td>H</td><td>H</td><td>CH₂Ph</td><td>Boo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 5</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-34-</td><td>^fcBoo</td><td>H</td><td>H</td><td>CH₂-indole-3-</td><td>Boo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 6</td><td></td><td></td><td></td><td>island</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-34-</td><td>^cBoo</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 7</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-34-</td><td>^fcBoo</td><td> ★</td><td>H</td><td> *</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 8</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>*R² and R^3b</td><td colspan="3">linked</td><td>together by (CH₂)3</td><td colspan="2">for</td><td colspan="2">form</td><td>ring</td><td>from</td><td></td><td></td>

five members.

Table III-35.

<td>N·</td><td>R¹</td><td>R²</td><td>_R3rd</td><td>_R3b</td><td>R⁴</td><td>R^yes</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>IH-35-1</td><td>Ph</td><td>H</td><td>H</td><td>H</td><td>Boo</td><td>H</td><td>CH₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-35-2</td><td>Ph</td><td>H</td><td>H</td><td>ch₃</td><td>Boo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-35-3</td><td>Ph</td><td>H</td><td>H</td><td>ch(ch₃)₂</td><td>Boo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>The</td><td>H</td><td>nh₂</td>

<td>III-35-4</td><td>Ph</td><td>H</td><td>H</td><td>CH₂CH (CH₃) ₂</td><td>Boo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 111-35-5</td><td>Ph</td><td>H</td><td>H</td><td>CH₂Ph</td><td>Boo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-35-6</td><td>Ph</td><td>H</td><td>H</td><td>CH₂ -indole-3-yl</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-35-7</td><td>Ph</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td>"Buu"</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 111-35-8</td><td>Ph</td><td> *</td><td>H</td><td> ★</td><td>Boo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

164/967 *R² and R^3b linked together by (CH₂)₃ to form a five-membered ring.

Table UI-36.

<td>No!</td><td>R¹</td><td>R²</td><td>_R3rd</td><td>R^3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>III- 36-1</td><td>p-Me- Ph</td><td>H</td><td>H</td><td>H</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>NH₂</td>

<td>III- 36-2</td><td>p-Me- Ph</td><td>H</td><td>H</td><td>ch₃</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III- 36-3</td><td>p-Me- Ph</td><td>H</td><td>H</td><td>CH(CH₃)₂</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III- 36-4</td><td>p-Me- Ph</td><td>H</td><td>H</td><td>ch₂ch(ch₃)₂</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III- 36-5</td><td>p-Me- Ph</td><td>H</td><td>H</td><td>CH₂Ph</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III- 36-6</td><td>p-Me- Ph</td><td>H</td><td>H</td><td>CH₂-indole-3yl</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III- 36-7</td><td>p-Me- Ph</td><td>H</td><td>H</td><td>ch₂ch₂school₃</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-</td><td>p-Me-</td><td> *</td><td>H</td><td> *</td><td>"Bu"</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

36-8 Ph *R² and R^3b linked together by (CH₂)₃ to form a ring of 5 five members.

Table UI-37.

<td>N'</td><td>R¹</td><td>R²</td><td>_R3rd</td><td>_R3b</td><td>R⁴</td><td>R⁵</td><td>r6</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>III-</td><td>Ph ft</td><td>H</td><td>H</td><td>H</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 37-1</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>pF-</td><td>H</td><td>H</td><td>ch₃</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 37-2</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>pF-</td><td>H</td><td>H</td><td>ch(ch₃)₂</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

37-3 Ph

165/967

<td>No</td><td>R¹</td><td>R²</td><td>R^3rd</td><td>_R3b</td><td>R⁴</td><td>R^and</td><td>and_R6</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>III-</td><td>pF-</td><td>H</td><td>H</td><td>CH₂CH(CH₃) ₂</td><td>Boo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 37-4</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>PF-</td><td>H</td><td>H</td><td>CH₂Ph</td><td>Boo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 37-5</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>pF-</td><td>H</td><td>H</td><td>CH₂-indole-3-</td><td>Boo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 37-6</td><td>Ph</td><td></td><td></td><td>island</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>pF-</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td>"Bu"</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 37-7</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>pF-</td><td> *</td><td>H</td><td> ★</td><td>Boo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 37-8</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>*R² and</td><td colspan="2">R^3b linked</td><td colspan="2">together by (CH₂)</td><td colspan="2">13 for</td><td colspan="2">form</td><td>ring</td><td>from</td><td></td><td></td>

five members.

Table III-38.

<td>N'</td><td>R¹</td><td>_r2</td><td>R^3rd</td><td>_R3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>III- 38-1</td><td>p-Cl- Ph</td><td>H</td><td>H</td><td>H</td><td>Boo</td><td>H</td><td>CH</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III- 38-2</td><td>p-Cl- Ph</td><td>H</td><td>H</td><td>CH₃</td><td>Boo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III- 38-3</td><td>p-Cl- Ph</td><td>H</td><td>H</td><td>CH(CH₃) 2</td><td>Boo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III- 38-4</td><td>p-Cl- Ph</td><td>H</td><td>H</td><td>CH₂CH(CH₃)₂</td><td>Boo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III- 38-5</td><td>p-Cl- Ph</td><td>H</td><td>H</td><td>CH₂Ph</td><td>Boo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III- 38-6</td><td>p-Cl- Ph</td><td>H</td><td>H</td><td>CH₂-indole-3yl</td><td>Boo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III- 38-7</td><td>p-Cl- Ph</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td>Boo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-</td><td>p-Cl-</td><td> ★</td><td>H</td><td> *</td><td>Boo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

166/967

<td>N'</td><td>R¹</td><td>R²</td><td>r3₃</td><td>R^3b</td><td>R⁴</td><td>R^yes</td><td> ; _Ryes</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td> 38-8</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>*R² and</td><td colspan="2">R^3b linked</td><td colspan="2">together by (CH₂)₃</td><td colspan="2">for</td><td colspan="2">form</td><td>ring</td><td>from</td><td></td><td></td>

<td>five</td><td>members</td><td> •</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td colspan="2">Table III-39</td><td> •</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>N'</td><td>R¹</td><td>R²</td><td>_R3rd</td><td>R^3b</td><td>R⁴</td><td>R^yes</td><td> ; _Ryes</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>III-</td><td>p-Br-</td><td>H</td><td>H</td><td>H</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>NH₂</td>

<td> 39-1</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>p-Br-</td><td>H</td><td>H</td><td>ch₃</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 39-2</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>p-Br-</td><td>H</td><td>H</td><td>ch(ch₃)₂</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 39-3</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>p-Br-</td><td>H</td><td>H</td><td>CH₂CH(CH₃) ₂</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 39-4</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>p-Br-</td><td>H</td><td>H</td><td>CH₂Ph</td><td>^r'Bu</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 39-5</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>p-Br-</td><td>H</td><td>H</td><td>CH₂-indole-3-</td><td>ⁿBoo</td><td>H</td><td>CH₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 39-6</td><td>Ph</td><td></td><td></td><td>island</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>p-Br-</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td>ⁿBU</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 39-7</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>p-Br-</td><td> *</td><td>H</td><td> *</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 39-8</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>*R² and</td><td colspan="2">R^3b linked</td><td colspan="2">together by (CH₂)₃</td><td colspan="2">for</td><td colspan="2">form</td><td>cinsl</td><td>from</td><td></td><td></td>

<td>five</td><td>members</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td colspan="2">Table III-40.</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>N'</td><td>R¹</td><td>_r2</td><td>_R3rd</td><td>_R3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>III-</td><td>pI-</td><td>H</td><td>H</td><td>H</td><td>Boo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 40-1</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>pI-</td><td>H</td><td>H</td><td>ch₃</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

40-2 Ph

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<td>N'</td><td>R¹</td><td>R²</td><td>R^3rd R^3b</td><td>R⁴</td><td>r^!</td><td>⁵ R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>III- 40-3</td><td>pI- Ph</td><td>H</td><td>H CH(CH₃)₂</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III- 40-4</td><td>pI- Ph</td><td>H</td><td>H CH₂CH(CH₃)₂</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III- 40-5</td><td>pI- Ph</td><td>H</td><td>H CH₂Ph</td><td>Boo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III- 40-6</td><td>pI- Ph</td><td>H</td><td>H CH₂-indole-3- island</td><td>Boo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III- 40-7</td><td>pI- Ph</td><td>H</td><td>H CH₂CH₂SCH₃</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III- 40-8</td><td>pI- Ph</td><td> *</td><td>H *</td><td>ⁿBoo</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td colspan="3">*R² and R^3b five members linked. Table III-41.</td><td>together by (CH₂)₃</td><td colspan="2">for</td><td colspan="2">form</td><td colspan="3">ring of</td><td></td>

<td>No</td><td>R¹</td><td>R² R</td><td>3a p3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>r9</td>

<td>III-41-1</td><td>ch₃</td><td>H H</td><td>H</td><td>Bz</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-41-2</td><td>ch₃</td><td>H H</td><td>ch₃</td><td>Bz</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-41-3</td><td>ch₃</td><td>H H</td><td>ch(ch₃)₂</td><td>Bz</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-41-4</td><td>ch₃</td><td>H H</td><td>CH₂CH(CH₃)₂</td><td>Bz</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-41-5</td><td>ch₃</td><td>H H</td><td>CH₂Ph</td><td>Bz</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-41-6</td><td>ch₃</td><td>H H</td><td>CH₂-indole-3-yl</td><td>Bz</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-41-7</td><td>ch₃</td><td>H H</td><td>CH₂CH₂SCH₃</td><td>Bz</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-41-8</td><td>ch₃</td><td>* H</td><td>•k</td><td>Bz</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td colspan="3">*R² and R^3b five members linked. Table III-42.</td><td>together by (CH₂)₃</td><td colspan="2">for</td><td colspan="2">form</td><td colspan="3">ring of</td><td></td>

<td>No</td><td>R¹</td><td>R² R³ⁱ</td><td>¹ R^3b</td><td>R⁴</td><td>R^yes</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

III-42-1 Et Η Η Η Βζ Η CH₃ F ΟΗ Η Η ΝΗ₂

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<td>No.</td><td>R¹</td><td>R²</td><td colspan="2">j^3b</td><td>R⁴</td><td>R⁵</td><td>R^yes</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>III-42-2</td><td>You</td><td>H</td><td>H</td><td>ch₃</td><td>Bz</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-42-3</td><td>You</td><td>H</td><td>H</td><td>CH(CH₃)₂</td><td>Bz</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 111-42-4</td><td>You</td><td>H</td><td>H</td><td>CH₂CH(CH₃)₂</td><td>Bz</td><td>H</td><td>ΓΊ-Γ UliJ</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-42-5</td><td>You</td><td>H</td><td>H</td><td>CH₂Ph</td><td>Bz</td><td>H</td><td>CH₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-42-6</td><td>You</td><td>H</td><td>H</td><td>CH₂-indole-3-yl</td><td>Bz</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-42-7</td><td>You</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td>Bz</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-42-8</td><td>You</td><td> *</td><td>H</td><td> *</td><td>Bz</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>*R² and R^3b</td><td colspan="3">linked</td><td>together by (CH₂)</td><td colspan="2">3 for</td><td colspan="2">form</td><td colspan="2">ring</td><td>from</td><td></td>

five members.

Table III-43.

<td>N' R¹</td><td>R²</td><td>_R3rd</td><td>_R3b</td><td>R⁴</td><td>R⁵</td><td>R^and</td><td>X</td><td>And</td><td>R⁷</td><td>r8</td><td>R⁹</td>

<td>III-43-1³P</td><td>The</td><td>H</td><td>H</td><td>Bz</td><td>The</td><td>CH₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>NH₂</td>

<td>III-43-2³P</td><td>H</td><td>H</td><td>ch₃</td><td>Bz</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>111-43-3 ip_r</td><td>H</td><td>H</td><td>ch(ch₃)₂</td><td>Bz</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-43-4³P</td><td>H</td><td>H</td><td>CH₂CH(CH₃)</td><td>2 Bz</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-43-5^xP</td><td>H</td><td>H</td><td>CH₂Ph</td><td>Bz</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 111-43-6 ^xP</td><td>H</td><td>H</td><td>CH₂-indole-</td><td>-3-row Bz</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-43-7^xP</td><td>H</td><td>H</td><td>ch₂ch₂school₃</td><td>Bz</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-43-8^xP</td><td> *</td><td>H</td><td> *</td><td>Bz</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td colspan="4">*R² and R^3b linked together by five members. Table III-44.</td><td colspan="2">(CH₂)₃ for</td><td colspan="2">form</td><td colspan="3">ring of</td><td></td>

<td>No. R¹</td><td>R²</td><td>R^3rd</td><td>_R3b</td><td>R⁴</td><td>R^Yes</td><td>R^yes</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>III-^fcBoo 44-1</td><td>H</td><td>H</td><td>H</td><td>Bz</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-^cBoo 44-2</td><td>H</td><td>H</td><td>ch₃</td><td>Bz</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III-^fcBoo</td><td>H</td><td>H</td><td>ch(ch₃)₂</td><td>Bz</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

44-3

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<td>No</td><td>R¹</td><td>R²</td><td>n3a Th 3b iv xx,</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>III- 44-4</td><td>^fcBoo</td><td>H</td><td>H CH₂CH(CH₃)₂</td><td>Bz</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III- 44-5</td><td>^cBoo</td><td>H</td><td>H CH₂Ph</td><td>Bz</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III- 44-6</td><td>^fcBoo</td><td>H</td><td>H CH₂indole-3- xIh</td><td>Bz</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III- 44-7</td><td>^cBoo</td><td>H</td><td>H CH₂CH₂SCH₃</td><td>Bz</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III - 44-8</td><td>^üBoo</td><td> *</td><td>H *</td><td>Bz</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>*R² and</td><td colspan="3">R^3b linked together by (CH₂)</td><td colspan="2">13 for</td><td colspan="2">form</td><td colspan="2">ring d(</td><td>I</td><td></td>

five members.

Table III-45.

<td>N'</td><td>R1</td><td>R²</td><td>_R3rd</td><td>R^3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>III- 45-1</td><td>Ph</td><td>The</td><td>The</td><td>The</td><td>Bz</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>NH₂</td>

<td>III- 45-2</td><td>Ph</td><td>The</td><td>The</td><td>ch₃</td><td>Bz</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III- 45-3</td><td>Ph</td><td>The</td><td>The</td><td>CH (CH₃) 2</td><td>Bz</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III- 45-4</td><td>Ph</td><td>The</td><td>The</td><td>ch₂ch (ch₃) ₂</td><td>Bz</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III- 45-5</td><td>Ph</td><td>The</td><td>The</td><td>CH₂Ph</td><td>Bz</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 45-6</td><td>Ph</td><td>The</td><td>The</td><td>CH₂-indole-3yl</td><td>Bz</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>III- 45-7</td><td>Ph</td><td>The</td><td>The</td><td>CH₂CH₂SCH₃</td><td>Bz</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td>11JC “</td><td>Ph</td><td> *</td><td>The</td><td> *</td><td>Bz</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

170/967

<td>N'</td><td>uncle H &amp; KJ</td><td>p3a p3b</td><td>R⁴</td><td>_r5</td><td>R^yes</td><td>X</td><td>And ]</td><td>R⁷</td><td>_r8</td><td>R⁹</td>

<td colspan="11"> 45-8</td>

<td>*R² and</td><td colspan="2">R^3b linked together by (</td><td colspan="2">CH₂) 3 for</td><td colspan="2">form</td><td>ring</td><td>from</td><td></td><td></td>

<td>five</td><td>members.</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td colspan="2">Table UI-46.</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>N'</td><td>R¹</td><td>R² R^3rd R^3b</td><td>R⁴</td><td>R~</td><td>' R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>III-</td><td>p-Me-</td><td>H H H</td><td>Bz</td><td>H</td><td>CH₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>NH₂</td>

<td> 46-1</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>11X “</td><td>p-Me-</td><td>H H CH₃</td><td>Bz</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 46-2</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>p-Me-</td><td>Η H CH(CH₃)₂</td><td>Bz</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 46-3</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>p-Me-</td><td>H h h₂ch(ch₃:</td><td> )₂ Bz</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 46-4</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>p-Me-</td><td>H H CH₂Ph</td><td>Bz</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 46-5</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>p-Me-</td><td>H H CH₂-indole</td><td>-3 - Bz</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 46-6</td><td>Ph</td><td>island</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>p-Me-</td><td>H H CH₂CH₂SCH_;</td><td>j Bz</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 46-7</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>p-Me-</td><td>*H*</td><td>Bz</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 46-8</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td> *_r2 θ</td><td colspan="2">R^3b linked together by (</td><td colspan="2">CH₂)₃ for</td><td colspan="2">form</td><td>ring</td><td>from</td><td></td><td></td>

<td>five</td><td>members.</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td colspan="2">Table UI-47.</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>Nt</td><td>R¹</td><td></td><td>R⁴</td><td>_r5</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td> 111 - 4 7</td><td>- pF-</td><td>H H H</td><td>Bz</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>NH₂</td>

<td> 1</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>UI-47</td><td>- PF-</td><td>H H CH₃</td><td>Bz</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

Ph

171/967

<td>N'</td><td>R¹</td><td>_R2</td><td>r33</td><td>_R3b</td><td>R⁴</td><td>R⁵</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>III-47-</td><td>pF-</td><td>H</td><td>H</td><td>CH(CH₃)₂</td><td>Bz</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>The</td><td>H</td><td>nh₂</td>

<td> 3</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>UI-47-</td><td>pF-</td><td>H</td><td>H</td><td>CH₂CH(CH₃)₂</td><td>Bz</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 4</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td> 111-47-</td><td>pF-</td><td>H</td><td>H</td><td>CH₂Ph</td><td>Bz</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 5</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>UI-47-</td><td>pF-</td><td>H</td><td>H</td><td>CH₂-indole-3-</td><td>Bz</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 6</td><td>Ph</td><td></td><td></td><td>island</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-47-</td><td>pF-</td><td>H</td><td>H</td><td>CH₂CH₂SCH₃</td><td>Bz</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 7</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>UI-47-</td><td>pF-</td><td> *</td><td>H</td><td> *</td><td>Bz</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 8</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>*R² and R</td><td colspan="2">^3b linked</td><td colspan="2">together by (CH₂)</td><td colspan="2">and 3 for</td><td colspan="2">form</td><td>ring</td><td>from</td><td></td><td></td>

<td colspan="2">five members.</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>Table</td><td>UI-48.</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>N'</td><td>R¹</td><td>R²</td><td>_R3rd</td><td>_R3b</td><td>R⁴</td><td>R^yes</td><td>R⁶</td><td>X</td><td>And</td><td>R⁷</td><td>R⁸</td><td>R⁹</td>

<td>III-</td><td>p-Cl-</td><td>H</td><td>H</td><td>H</td><td>Bz</td><td>H</td><td>ch₃</td><td>F</td><td>OH</td><td>H</td><td>H</td><td>nh₂</td>

<td> 48-1</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>III-</td><td>p-Cl-</td><td>H</td><td>H</td><td>ch₃</td><td>Bz</td><td>H</td><td>ch₃</td><td>F</td><td>oh</td><td>H</td><td>H</td><td>nh₂</td>

<td> 48-2</td><td>Ph</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>