8-[3-amino-piperidin-1-yl]-xanthines, the production thereof and the use of the same as medicaments

(74) Agent

Boehringer Ingelheim Pharma GmbH & Co. KG, Postfach 200, DE-55218 INGELHEIM AM RHEIN, Germany

Frank Himmelsbach, Ahornweg 16, DE-88441 MITTELBIBERACH, Germany

Roland Maier, Bodelschwingstrasse 39, DE-88400 BIBERACH AND RISS, Germany

Elke Langkopf, Schloss 3, DE-88447 WARTHAUSEN, Germany

Matthias Eckhardt, Kirschenweg 7, DE-88400 BIBERACH, Germany

Ralf Richard Hermann Lotz, Schluesslerstrasse 28, DE-88433 SCHEMMERHOFEN, Germany

Mohammad Tadayyon, SchUlinstrasse 31, DE-89083 ULM, Germany

Michael Mark, Hugo-Haering-Strasse 50, DE-88400 BIBERACH AND RISS, Germany

Bryn Aarflot AS, PO Box 449 Center, 0104 OSLO, Norway

<td> (54)</td><td>Designation</td><td>8- [3-Amino-piperidin-1-yl] -xanthines, preparation thereof, and process for the preparation of a pharmaceutical composition</td>

<td> (56)</td><td>cited publications</td><td>NO 20033726 A</td>

<td> (57)</td><td>Summary</td><td></td>

The present invention relates to substituted xanthines of the general formula III

<img file="NO336641B1_D0001.tif" />

R² wherein R 1 to R 3 are defined as in claim 1, as intermediates for the preparation of compounds having inhibitory effect on the activity of the enzyme dipeptidyl peptidase-IV (DPP-IV).

In the present specification, reference is made to newly substituted xanthines of the general formula

<img file="NO336641B1_D0002.tif" />

the tautomers, stereoisomers, mixtures, prodrugs thereof and the salts thereof, in particular the physiologically acceptable salts thereof with inorganic or organic acids or bases, which have valuable pharmacological properties, in particular an inhibitory effect on the activity of the enzyme dipeptidyl peptidase-IV (DPP-IV), the preparation of these, their use for the prevention or treatment of diseases or disorders related to increased DPP-IV activity or which can be prevented or alleviated by reduction of DPP-IV activity, especially type I or type Π diabetes mellitus, the pharmaceutical compositions containing a compound thereof. general formula (I) or a physiologically acceptable salt thereof, as well as methods of preparation thereof.

The present invention is described in the appended claims.

Accordingly, the present invention relates to a compound of formula (ΠΙ), or an enantiomer thereof

<img file="NO336641B1_D0003.tif" />

where

R 1 is 4-methyl-2-quinazolinylmethyl, R 2 is methyl and R 3 is 2-butyn-1-yl.

Furthermore, the present invention relates to a process for the preparation of a compound

<img file="NO336641B1_D0004.tif" />

R 1 is 4-methyl-2-quinazolinylmethyl,

R 2 is methyl and R 3 is 2-butyn-1-yl;

characterized in that a corresponding compound of formula (ΠΙ) is deprotected.

Furthermore, the present invention relates to a process for the preparation of a pharmaceutical composition according to the claims.

In formula I above, R¹ a methyl group, a methyl group substituted with a dimethylaminocarbonyl, pyrrolidin-1ylcarbonyl, piperidin-1-ylcarbonyl, tert-butylcarbonyl or a cyclohexylcarbonyl group, a methyl group substituted with a naphthyl, methyl naphthyl, methyl naphthyl, methyl naphthyl, - or dimethylaminonaphthyl group, a methyl group substituted with a 2-phenylethenyl or a biphenylyl group, a methyl group substituted with a phenyloxadiazolyl, 5-methyl-3-phenyl-isoxazolyl, phenylpyridinyl, indolyl, benzothiophenyl, quinolinyl, isoquinolinyl, methylisoquinolinyl, (methoxycarbonylmethylamino) -isoquinolinyl, cinnolinyl, quinazolinyl, methylquinazolinyl,

1,2-dihydro-1-methyl-2-oxo-quinolinyl-, 1,2-dihydro-2-methyl-1-oxo-isoquinolinyl-, 3,4-dihydro-4-oxo-phthalazinyl-, 3,4 -dihydro-3-methyl-4-oxo-phthalazinyl-, 3,4-dihydro-4-oxo-quinazolinyl-, 3,4-dihydro-3-methyl-4-oxo-quinazolinyl- or a 2-oxo-2H-chromenyl group, a 2-methoxyethyl, 2-phenyloxyethyl or 2-cyanoethyl group, a phenylcarbonylmethyl or a 1- (phenylcarbonyl) ethyl group, a phenylcarbonylmethyl group wherein the phenyl group is substituted by an amino, cyanomethylamino, methylcarbonylamino, ethylcarbonylamino-, isopropylcarbonylamino-, methoxycarbonylamino- (ethyloxycarbonylamino) -carbonylamino- or a 2-oxoimidazolidin-1-yl group, a phenylcarbonylmethylcarbonylmethylcarbonylamino-carbonylmethylcarbonylmethoxycarbonylmethoxycarbonylmethoxycarbonylmethyl - or morpholine-4-ylcarbonyl group, a phenylcarbonylmethyl group, wherein the phenyl group is substituted with a methylsulfanyl, methylsulfmyl or methylsulfonyl group, one fenylkarbonylmetylgruppe wherein the phenyl group is substituted with a karboksymetoksy-, etyloksykarbonylmetoksy-, isopropyloksykarbonylmetoksy-, aminokarbonylmetoksy-, metylaminokarbonylmetoksy-, etylaminokarbonylmetoksy-, isopropylaminokarbonylmetoksy-, dimetylaminokarbonylmetoksy-, pyrrolidin-ylkarbonylmetoksy- or morpholin-4-ylkarbonylmetoksygruppe, one fenylkarbonylmetylgruppe wherein the phenyl group is substituted by a 1 (methoxycarbonyl) -ethyloxy or a 1- (aminocarbonyl) -ethyloxy group, a phenylcarbonylmethyl group wherein the phenyl group is substituted with a methylsulfylmethylmethoxy group, a phenylcarbonylmethyl group, where the phenyl group is substituted with two methoxy groups or a phenylcarbonylmethyl group, where two hydrogen atoms in a neighboring position in the phenyl group are replaced by an -O-CH- CH2 -O- or a -N (CH3) -CO-O group,

R² means a hydrogen atom, a methyl, isopropyl, 2-propen-1-yl, 2-propyn-1-yl or phenyl group or a cyanomethyl or methoxycarbonylmethyl group and

R³ means a 2-cyanobenzyl or 2,6-dicyanobenzyl group, a 2-methyl-2-propen-1-yl-, 2-chloro-2-propen-1-yl- or 3-bromo-2-propylene-1-yl. yl group a 2-buten-1-yl, 3-methyl-2-buten-1-yl or 2,3-dimethyl-2-buten-1-yl group, a 2-butyn-1-yl group, a 1- cyclopenten-1-ylmethyl group or a 2-furanylmethyl group.

The carboxy groups mentioned in the definition of the above groups can be replaced by a group which can be converted to a carboxy group in vivo or with a group negatively charged under physiological conditions, and furthermore, the amino and imino groups mentio ned in the definition of the the above groups, being substituted with a group which can be cleaved in vivo. Such groups are described, for example, in WO 98/46576 and by NM Nielsen et al. in International Journal of Pharmaceutics 39, 75-85 (1987).

Compounds containing a group that can be cleaved in vivo are prodrugs of the corresponding compounds where this group which can be cleaved in vivo is cleaved.

By a group which can be converted in vivo to a carboxy group is meant, for example, a hydroxymethyl group, a carboxy group esterified with an alcohol, the alcohol group being preferably a C 1-6 alkanol, a phenyl C 1-3 alkanol, a C 3-9 group. cycloalkanol, while a C5-8 cycloalkanol may additionally be substituted with one or two C1-3 alkyl groups, a C5-8 cycloalkanol where a methylene group at the 3 or 4 position is replaced by an oxygen atom, or with an imino group optionally substituted with a C1-3 alkyl, phenylC1-3 alkyl, phenyl C1-3 alkyloxycarbonyl or C2 -6 alkanoyl group, and the cycloalkanol group may additionally be substituted by one or two C 1-3 alkyl groups, one

C4-7-cycloalkenol, a C3-s-alkenol, a phenyl-C3-5-alkenol, a C3-s-alkynol or phenylC3-5-alkynol, with the proviso that no bonds to the oxygen atom originate from a carbon atom bearing a carbon atom. double or triple bond, a C3-8 cycloalkyl C1-3 alkanol, a bicycloalkanol having a total of 8 to 10 carbon atoms, which may additionally be substituted in the bicycloalkyl group by one or two C1-3 alkyl groups, a 1,3- dihydro-3-oxo-lisobenzofuranol or an alcohol of formula

Rp-CO-O- (RqCRr) -OH, where

R_P means a C 1-8 alkyl, C 3-7 cycloalkyl, C 1-8 alkyloxy, C 3-7 cycloalkyloxy, phenyl or phenyl C 1-3 alkyl group,

R 5 represents a hydrogen atom, a C 1-3 alkyl, C 3-7 cycloalkyl or phenyl group and

Rr means a hydrogen atom or a C 1-3 alkyl group, with a group negatively charged under physiological conditions, is meant, for example, a tetrazol-5-yl, phenylcarbonylaminocarbonyl, trifluoromethylcarbonylaminocarbonyl, C 1-6 alkylsulfonylamino, phenylsulfonylamino, benzylsulfonylamino, trifluoromethylsulfonylamino, C 1-6 alkylsulfonylaminocarbonyl, phenylsulfonylaminocarbonyl, benzylsulfonylaminocarbonyl or perfluoroC 1-6 alkylsulfonylaminocarbonyl group, and by a group which can be cleaved in vivo from an imino or amino group is meant, for example, a hydroxy group, an acyl group such as a phenylcarbonyl group optionally mono- or disubstituted with fluorine, chlorine, bromine or iodine atoms, with C 1.3 -alkyl or C 1-3 alkoxy groups, wherein the substituents may be the same or different, a pyridinoyl group or a C 1-6 alkanoyl group such as a formyl, acetyl, propionyl, butanoyl, pentanoyl or hexanoyl group, a 3,3,3-trichloropropionyl or allyloxycarbonyl group, a C 1-6 alkoxycarbonyl or C 1-6 alkylcarbonyloxy group, wherein the hydrogen atoms may be completely or partially replaced by fluorine or chlorine atoms such as a methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl -, isopropoxycarbonyl, butoxycarbonyl, tert-butoxycarbonyl, pentoxycarbonyl, hexoxycarbonyl, octyloxycarbonyl, nonyloxycarbonyl, decyloxycarbonyl, undecyloxycarbonyl, dodecyloxycarbonyl, hexadecylo metylkarbonyloksy-, etylkarbonyloksy-, 2,2,2-trikloretylkarbonyloksy-, propylkarbonyloksy-, isopropylkarbonyloksy-, butylkarbonyloksy-, tert butylkarbonyloksy-, pentylkarbonyloksy-, heksylkarbonyloksy-, oktylkarbonyloksy-, nonylkarbonyloksy-, decylkarbonyloksy-, undecylkarbonyloksy-, dodecylkarbonyloksy- or hexadecylcarbonyloxy group, a phenylC 1-6 alkoxycarbonyl group such as an enyloxycarbonyl, phenylethoxycarbonyl or phenylpropoxycarbonyl group, a 3-amino-propionyl group, wherein the amino group may be mono- or disubstituted with C1-6 alkyl or C3-7 cycloalkyl groups and the substituents may be the same or different, a C1-3 alkylsulfonyl-C2-4 alkoxycarbonyl-, C1-3 alkoxy-C2 -4-alkoxy-C2-4-alkoxycarbonyl-, Rp-CO-O- (RqCRr) -O-CO-, C1-6 alkylCO-NH- (RsCRt) -O-CO- or C1-6 alkyl- CO-O- (RsCRt) - (RsCRt) -O-CO group, wherein Rp to Rr are as defined above,

R5 and Rt, which may be the same or different, mean hydrogen atoms or C1-3 alkyl groups.

A first article of the present disclosure relates to compounds of general formula (I) wherein

R¹ means a methyl group substituted with a dimethylaminocarbonyl, pyrrolidin-1ylcarbonyl, piperidin-1-ylcarbonyl, tert-butylcarbonyl or a cyclohexylcarbonyl group, a methyl group substituted with a naphthyl, methylnaphthyl, nitoxynaphthyl, methoxynaphthyl, (dimethylamino) naphthyl group, a methyl group substituted with a 2-phenylethenyl or a biphenylyl group, a methyl group substituted with a phenyl-oxadiazolyl, 5-methyl-3-phenylisoxazolyl, phenyl-pyridinyl, indolyl, benzothiophenyl, quinolinyl, isoquinolinyl, methylisoquinolinyl, (methoxycarbonylmethylamino) -isoquinolinyl, cinnolinyl, quinazolinyl, methylquinazolinyl, 1,2-dihydro-1-methyl-2-oxo-quinolinyl, 2-dihydro-2-methyl-1-oxoisoquinolinyl-, 3,4-dihydro-4-oxo-phthalazinyl-, 3,4-dihydro-3-methyl-4-oxo-phthalazinyl-, 3,4-dihydro-4 -oxo-quinazolinyl, 3,4-dihydro-3-methyl-4-oxo-quinazolinyl or a 2-oxo2H-chromenyl group, a 2-methoxyethyl, 2-phenyloxyethyl or 2-cyanoethyl group, a phenylcarbonylmethyl or a 1- (phenylcarbonyl) ethyl group, a phenylcarbonylmethyl group, wherein the phenyl group is substituted with an amino, cyanomethylamino, methylcarbonylamino, ethylcarbonylamino, isopropylcarbonylamino, methoxycarbonylamino, methoxycarbonylamino, oxoimidazolidin-1-yl group, a phenylcarbonylmethyl group, wherein the phenyl group is substituted with a carboxy, methoxycarbonyl, ethyloxycarbonyl, aminocarbonyl, methylaminocarbonyl, for example, dimethylaminocarbonyl or morpholin-4-ylcarbonyl group, a phenylcarbonylmethyl group, wherein the phenyl group is substituted with a methylsulfanyl, methylsulfonyl or methylsulfonylmethoxycarbonylmethoxylmethoxymethylmethoxymethylmethoxy ethylaminocarbonylmethoxy, isopropylaminocarbonylmethoxy, dimethylaminocarbonylmethoxy, pyrrolidin-1-ylcarbonylmethoxy or morpholine-4-ylcarbonylmethoxy group, a phenylcarbonylmethyl group wherein the phenyl group is substituted with a 1 (methoxycarbonyl) -ethyloxy or a 1- (aminocarbonyl) -ethyloxy group, a phenylcarbonylmethyl group, a phenylcarbonylmethyl group, a phenylcarbonylmethyl group a phenylcarbonylmethyl group, wherein the phenyl group is substituted by two methoxy groups, or a phenylcarbonylmethyl group, wherein two hydrogen atoms are adjacent to the phenyl group, is replaced by an -O-CH 2 -O-, -O-CH 2 -CH 2 -O- or a -N (CH 3) -CO-O group,

R² means a methyl, isopropyl or phenyl group and

R³ a 2-methyl-2-propen-1-yl-, 2-chloro-2-propen-1-yl or 3-bromo-2-propenylyl group means a 2-buten-1-yl or 2.3 -dimethyl-2-buten-1-yl group, a 2-butyn-1-yl group, a 1-cyclopenten-1-ylmethyl group or a 2-furanylmethyl group as well as the compounds

- (2-cyano-ethyl) -3-methyl-7- (2-cyano-benzyl) -8- (3-amino-piperidin-1-yl) -xanthine, 1- (2- {2 - [(ethoxycarbonyl) ) methoxy] -phenyl} -2-oxo-ethyl) -3-methyl-7- (3-methyl-2-buten-1-yl) 8- (3-amino-piperidin-1-yl) -xanthine, 1 - (2- {2 - [(aminocarbonyl) methoxy] phenyl} -2-oxo-ethyl) -3-methyl-7- (3-methyl-2-buten-1-yl) 8- (3-amino) piperidin-1-yl) -xanthine, 1- (2- {3 - [(methanesulfmyl) methoxy] phenyl} -2-oxo-ethyl) -3-methyl-7- (3-methyl-2-butene-1 -yl) -8 (3-amino-piperidin-1-yl) -xanthine,

- (1-methyl-2-oxo-2-phenyl-ethyl) -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) - xanthine, 1- (2-phenoxy-ethyl) -3-methyl-7- (2-cyano-benzyl) -8- (3-amino-piperidin-1-yl) -xanthine,

- (2-phenyl-2-oxo-ethyl) -7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine, 1- (2- {3 - [(Ethoxycarbonyl) methoxy] -phenyl} -2-oxo-ethyl) -3-methyl-7- (3-methyl-2-buten-1-yl) 8- (3-amino-piperidin-1-yl) yl) -xanthine, 1- (2- {2 - [(methylaminocarbonyl) methoxy] -phenyl} -2-oxo-ethyl) -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine,

- (2- {2 - [(dimethylaminocarbonyl) methoxy] phenyl} -2-oxoethyl) -3-methyl-7- (3-methyl-2butene-1-yl) - 8- (3-amino-piperidine -1-yl) -xanthine, 1- (2-methoxy-ethyl) -3-methyl-7- (2-cyano-benzyl) -8- (3-amino-piperidin-1-yl) -xanthine, 1- methyl 3 - [(methoxycarbonyl) methyl] -7- (2-cyano-benzyl) -8- (3-amino-piperidin-1-yl) xanthine, 1-methyl-3-cyanomethyl-7- (2-cyano -benzyl) -8- (3-amino-piperidin-1-yl) -xanthine, 1-methyl-3- (2-propyn-1-yl) -7- (2-cyano-benzyl) -8- (3 -amino-piperidin-l-yl) -xanthine,

- {2- [3- (2-oxo-imidazolidin-1-yl) -phenyl] -2-oxo-ethyl} -3-methyl-7- (3-methyl-2-buten-1-yl) (3-Amino-piperidin-1-yl) -xanthine, 1-methyl-3- (2-propen-1-yl) -7- (2-cyano-benzyl) -8- (3-amino-piperidin-1) -yl) -xanthine, 1- (2- {2 - [(ethylcarbonyl) amino] -phenyl} -2-oxo-ethyl) -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine, 1-methyl-3-phenyl-7- (2-cyano-benzyl) -8- (3-amino-piperidin-1-yl) -xanthine, l- [2- (2-amino-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-butene-l-yl) -8 - ((* S) -3- aminopiperidin-1-yl) -xanthine,

- (2-phenyl-2-oxo-ethyl) -3-cyanomethyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine, 1- [(quinolin-2-yl) methyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) xanthine, 1 - [( 2-oxo-27β-chromene- 4-yl) methyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-aminopiperidin-1-yl) -xanthine,

- [(Cinnolin-4-yl) methyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) xanthine, 1- [ (1-methyl-2-oxo-1,2-dihydro-quinolin-4-yl) methyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8 (3-amino) piperidin-1-yl) -xanthine, 1 - [(4-oxo-3,4-dihydro-flalazin-1-yl) methyl] -3-methyl-7- (3-methyl-2-buten-1-yl) ) -8- (3-aminopiperidin-1-yl) -xanthine, 1 - [(quinazolin-4-yl) methyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8 - (3-amino-piperidin-l-yl) xanthine,

- [(5-methyl-3-phenyl-isoxazol-4-yl) methyl] -3-methyl-7- (3-methyl-2-buten-1-yl) - 8- (3-aminopiperidin-1-yl) yl) -xanthin, 1 - [(isoquinolin-3-yl) methyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) ) xanthine,

- [(3-phenyl- [1,2,4] oxadiazol-5-yl) methyl] -3-methyl-7- (3-methyl-2-buten-1-yl) - 8- (3-aminopiperidine - (1-yl) -xanthine,

- [(4-phenyl-pyridin-2-yl) methyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine ,

- [(5-phenyl-pyridin-2-yl) methyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine , 1 - [(3-methyl-4-oxo-3,4-dihydro-flalazin-1-yl) methyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8 ( 3-amino-piperidin-1-yl) -xanthine,

- [2- (3-methylsulfanyl-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-aminopiperidin-1-yl) xanthine,

- [2- (3-methanesulfinyl-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-aminopiperidin-1-yl) ) -xanthine

- [2- (3-Methanesulfony-1-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) - 8- (3-aminopiperidine-1-yl) yl) -xanthine, 1- [2- (3-carboxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3- amino (piperidin-1-yl) -xanthine,

- [2- (3-methoxycarbonyl-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) ) -xanthine, 1- {2- [3- (methylaminocarbonyl) -phenyl] -2-oxo-ethyl} -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3amino) -piperidin-1-yl) -xanthine,

- {2- [3- (Dimethylaminocarbonyl) -phenyl] -2-oxo-ethyl} -3-methyl-7- (3-methyl-2-buten-1-yl) -8 (3-amino-piperidine-1 -yl) -xanthine, 1- {2- [3- (morpholin-4-yl-carbonyl) -phenyl] -2-oxo-ethyl} -3-methyl-7- (3-methyl-2-butene-1 -yl) -8 (3-amino-piperidin-1-yl) -xanthine, 1- [2- (2-carboxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl- 2-Buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine, 1- [2- (2-ethoxycarbonyl-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-aminopiperidin-1-yl) -xanthine,

1 - {2- [2- (Dimethylaminocarbonyl) phenyl] -2-oxoethyl} -3-methyl-7- (3-methyl-2-buten-1-yl) -8 (3-amino-piperidine-1 -yl) -xanthine, 1- {2- [2- (morpholin-4-yl-carbonyl) -phenyl] -2-oxo-ethyl} -3-methyl-7- (3-methyl-2-butene-1 -yl) -8 (3-amino-piperidin-1-yl) -xanthine,

1- [2- (2,6-Dimethoxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-aminopiperidin-1 -yl) -xanthine, 1- ((E) -3-phenyl-allyl) -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1 yl) -xanthine,

- [(benzo [Z&gt;] thiophen-3-yl) methyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthin, 1 - [(7-indol-3-yl) methyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1 -yl) xanthine, 1 - [(biphenyl-4-yl) methyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) ) xanthine,

- (2-Cyclohexyl-2-oxo-ethyl) -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine, 1 - (3,3-dimethyl-2-oxo-butyl) -3-methyl-7- (3-methyl-2-buten-yl) -8- (3-amino-piperidin-yl) -xanthine,

- ({5 - [(methoxycarbonyl) methylamino] -isoquinolin-1-yl} methyl) -3-methyl-7- (3-methyl-2butene-1-yl) - 8- (3-amino-piperidine-1-yl) yl) -xanthin, 1- (2-dimethylamino-2-oxo-ethyl) -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidinyl) -xanthine, 1- [2- (piperidin-1-yl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino) piperidinl-yl) -xanthine, 1 - [(2-methyl-1-oxo-1,2-dihydro-isoquinolin-4-yl) methyl] -7- (3-methyl-2-buten-1-yl) - 8- (3 amino-piperidin-1-yl) -xanthine, l- [2- (2,3-dimethoxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-butene-l-yl) -8- (3-aminopiperidine-1 yl) -xanthine,

- [2- (pyrrolidin-1-yl) -2-oxo-ethyl] -3-methyl 1-7- (3-methyl-2-buten-1-yl) -8- (3-aminopiperidin-1 - yl) -xanthine, 1- [2- (2,3-dihydro-benzo [1,4] dioxin-5-yl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2- buten-1-yl) -8 (3-amino-piperidin-1-yl) -xanthine, 1- [2- (3-methyl-2-oxo-2,3-dihydro-benzooksazol-7-yl) -2 -oxo-ethyl] -3-methyl-7- (3-methyl-2butene-1-yl) - 8- (3-amino-piperidin-1-yl) -xanthine,

- [2- (benzo [1,3] dioxol-4-yl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) - 8- (3 -aminopiperidin-1-yl) -xanthine, 1-methyl-3-isopropyl-7- (2-cyano-benzyl) -8- (3-amino-piperidin-1-yl) -xanthine,

1- [2- (2-cyanomethylamino-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) ) -xanthine

- [(isoquinolin-1-yl) methyl] -3 - [(methoxycarbonyl) methyl] -7- (3-methyl-2-buten-1-yl) -8- (3 amino-piperidin-1-yl) -xanthine ,

- (2- {2 - [(isopropyloxycarbonyl) methoxy] phenyl} -2-oxoethyl) -3-methyl-7- (3-methyl-2butene-1-yl) - 8- (3-amino-piperidine -1-yl) -xanthine,

- [2- (2- {[(ethoxycarbonylamino) carbonyl] amino} -phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3- amino-piperidin-1-yl) -xanthine,

- [2- (2-acetylamino-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8 - ((O) -3-aminopiperidine - 1-yl) -xanthine, 1- (2- {2 - [(methylaminocarbonyl) methoxy] -phenyl} -2-oxo-ethyl) -3-methyl-7- (3-methyl-2-buten1-yl) -8 - ((S) -3-amino-piperidin-1-yl) -xanthine,

-methyl-7- (2-cyano-benzyl) -8- (3-amino-piperidin-1-yl) -xanthine,

- (2- {2 - [(isopropylcarbonyl) amino] phenyl} -2-oxo-ethyl) -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino) piperidin-1-yl) -xanthine, 1- (2- {2 - [(methoxycarbonyl) amino] phenyl} -2-oxo-ethyl) -3-methyl-7- (3-methyl-2-butene-1 -yl) 8- (3-Amino-piperidin-1-yl) -xanthine, 1- [2- (3-methyl-2-oxo-2,3-dihydro-benzooksazol-4-yl) -2-oxo- ethyl] -3-methyl-7- (3-methyl-2butene-1-yl) - 8- (3-amino-piperidin-1-yl) -xanthine,

- [2- (2-nitro-3-methoxy-phenyl) -2-oxo-ethyl 1] -3-methyl-7- (3-methyl-2-buten-1-yl) - 8- (3- aminopiperidin-1-yl) -xanthine, 1- [2- (2-amino-3-methoxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-butene-1- yl) -8- (3-amino-piperidin-1-yl) -xanthine, 1- [2- (2-oxo-2,3-dihydro-benzooksazol-7-yl) -2-oxo-ethyl] -3-methyl -7- (3-methyl-2-butenyl) -8- (3-amino-piperidin-1-yl) -xanthine,

- [(3-methyl-isoquinolin-1-yl) methyl] -3-methyl 1-7- (3-methyl-1-buten-1-yl) -8 - ((7?) - 3-aminopiperidine-1 yl) -xanthine,

- [(3-methyl-isoquinolin-1-yl) methyl] -3-methyl-7- (2-cyano-benzyl) -8- (3-amino-piperidin-1-yl) -xanthine, 1- [2- (3-carboxymethoxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine and 1 - [2- (2-carboxymethoxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine, the tautomers, the enantiomers, the diastereomers, their mixtures, their prodrugs and the salts thereof.

A first preferred subgroup of the first article of the present disclosure comprises compounds of general formula I, wherein

R¹ means a 4-methoxy-1-naphthylmethyl group, a 2-quinolinylmethyl, 4-quinolinylmethyl or a 6-quinolinylmethyl group, a 1-isoquinolinylmethyl, 3-methyl-1-isoquinolinylmethyl, 4-methyl-1-isoquinolinylmethyl or a 3-isoquinolinylmethyl group or a 2-quinazolinylmethyl, 4-methyl-2-quinazolinylmethyl or a 4-quinazolinylmethyl group,

R² means a methyl group and

R³ means a 2-buten-1-yl or a 2-butyn-1-yl group, the tautomers, enantiomers, diastereomers, mixtures thereof and the salts thereof.

Another preferred subgroup of the first article of the present disclosure comprises compounds of general formula I, wherein

R¹ means a [2- (methylcarbonylamino) -phenyl] -carbonylmethyl group, a [2- (ethylcarbonylamino) -phenyl] -carbonylmethyl group, or a [2- (isopropylcarbonylamino) -phenyl] -carbonylmethyl group,

R² means a methyl group and

R³ means a 2-buten-1-yl or a 2-butyn-1-yl group, the tautomers, enantiomers, diastereomers, mixtures thereof and the salts thereof.

A third preferred subgroup of the first article according to the present disclosure comprises compounds of the general formula I according to claim 1, wherein

R¹ means a [2- (aminocarbonylmethoxy) phenyl] carbonylmethyl group, a [2- (methylaminocarbonylmethoxy) phenyl] carbonylmethyl group, a [2- (ethylaminocarbonylmethoxy) phenyl] carbonylmethyl group or a [2- (isopropylaminocarbonylmethoxy) -karbonylmetylgruppe,

R² means a methyl group and

R³ means a 2-buten-1-yl group, a 2-butyn-1-yl group or a 1-cyclopenten-1-ylmethyl group, the tautomers, enantiomers, diastereomers, mixtures thereof and the salts thereof.

A second article according to the present disclosure relates to compounds of general formula I, wherein

R¹ means a methyl group substituted with a naphthyl, fluoro naphthyl, methyl naphthyl, methoxynaphthyl, (difluoromethoxy) naphthyl, cyano naphthyl, nitronaphthyl or (dimethylamino) naphthyl group, a methyl group substituted with a phenanthrenyl group, is substituted with a 2-phenylethenyl, 2 - [(trifluoromethyl) -phenyl] -ethenyl-, 2- (nitrophenyl) ethenyl, 2- (pentafluorophenyl) ethenyl or a biphenylyl group, a methyl group substituted with a phenyloxadiazolyl phenylpyridinyl, indolyl, methylindolyl, dimethyl-6,7-dihydro-5? - [2] pyrindinyl, benzimidazolyl, methylbenzimidazolyl- (cyanoethyl) -benzimidazolyl- (methylaminocarbonylmethyl) benzimidazolyl-, benzylbenzimidobenzyl cyanobenzofuranyl, benzoxazolyl, nitrobenzoxazolyl, benzothiophenyl, methylbenzothiazolyl, quinolinyl, methoxykinolinyl, isoquinolinyl, methylisoquinolinyl, (difluoromethyl) isoquinolinyl, (trifluoromethyl), (1-cyanol-methyl-ethyl) isoquinolinyl-, phenylisoquinolinyl-, methoxyisoquinolinyl-, methoxy-chloro-isoquinolinyl-, methoxy-bromo-isoquinolinyl- (methoxycarbonylmethylamino) -isoquinolinyl-, dimethyl-5,6,7,8-tetrahydro- 1,2,3,4-tetrahydrophenanthridinyl-, cinnolinyl-, quinazolinyl-, methylquinazolinyl-, isopropylquinazolinyl-, cyclopropylquinazolinyl-, phenylquinazolinyl-, aminokinazolinyl- (dimethylamino) -quinazolinyl-pyrrolidin-1-pyrrolidinyl , piperazin-1-ylquinazolinyl-, morpholine-4ylquinazolinyl, ethoxycinazolinyl, isopropyloxycinazolinyl, phenyloxycinazolinyl, imidazo [1,2-a] pyridinyl, methylimidazo [1,2-a] pyridinyl, phenylimidazo [1,2-a] benzyl , 2-a] pyridinyl, pyrazolo [1,5-a] pyridinyl, quinoxalinyl, methylquinoxalinyl, dimethylquinoxalinyl, trimethylquinoxalinyl, phenylquinoxalinyl, methylphthalazinyl, naphthyridinyl, 2,3-benzyl 4] dioxinyl- 1,2 1,2-dihydro-2-oxoquinolinyl- 1,2-dihydro-1-methyl-2-oxo-quinolinyl- 1,2-dihydro-2-methyl-1-oxoisoquinolinyl-, 3,4-dihydro-4-oxo-phthalazinyl-, 3,4-dihydro-3-methyl-4-oxo-phthalazinyl-, 3,4-dihydro-4 -oxo-quinazolinyl, 3,4-dihydro-3-methyl-4-oxo-quinazolinyl or a 2-oxo-2H-chromenyl group, a phenylcarbonylmethyl group, a phenylcarbonylmethyl group, wherein the phenyl group is substituted with an amino, cyanomethylamino ) amino, (methylaminocarbonyl) methylamino, methylcarbonylamino, ethylcarbonylamino, isopropylcarbonylamino, phenylcarbonylamino, methoxycarbonylamino- (ethyloxycarbonylamino) carbonylamino or a 2-oxo-imidazolidin-1-yl group, a phenylcarbonylmethyl group, wherein the phenyl group is substituted with a phenyl group, a phenylcarbonylmethyl group, wherein the phenyl group is substituted by a carboxylic acid, , methylaminocarbonyl, dimethylaminocarbonyl or morpholine-4-ylcarbonyl group, a phenylcarbonylmethyl group wherein the phenyl group is substituted with a methylsulfanyl, metylsulfmyl- or methylsulfonyl one fenylkarbonylmetylgruppe wherein the phenyl group is substituted by a methoxy, difluoromethoxy, trifluoromethoxy, etyloksy-, isopropyloksy- or aryloxy group, one fenylkarbonylmetylgruppe wherein the phenyl group is substituted with a metylsulfmylmetoksy-, karboksymetoksy-, etyloksykarbonylmetoksy-, isopropyloksykarbonylmetoksy -, aminocarbonylmethoxy, methylaminocarbonylmethoxy, ethylaminocarbonylmethoxy, isopropylaminocarbonylmethoxy, dimethylaminocarbonylmethoxy, pyrrolidin-1-ylcarbonylmethoxy or morpholine-4ylcarbonylmethoxy group, a phenylcarbonylmethyl group, wherein the phenyl group is substituted with a 1- (ethyloxycarbonyl) -1-methyl-ethyloxy-, 1- (methoxycarbonyl) ) ethyloxy group, a phenylcarbonylmethyl group wherein the phenyl group is substituted by two methoxy groups, a phenylcarbonylmethyl group, wherein the phenyl group is substituted with a methoxy group and a nitro group, a phenylcarbonylmethyl group, wherein the phenyl group is substituted by a methoxy group and an amino group, a phenylcarbonylmethyl group, wherein two hydrogen atoms adjacent to the phenyl group are replaced by one-O-CH₂-O-, -O-CF 2 -O-, -O-CH 2 -CH 2 -O-, -NH-CO-NH-, -N (CH₃) -CONH-, -N (CH₃) -CO-N (CH₃) -, -NH-CO-O- or an -N (CH₃) -CO-O group, a (2-phenylethyl) carbonylmethyl group, a naphthylcarbonylmethyl, indolylcarbonylmethyl or quinolinylcarbonylmethyl group or a 2-cyanimino-2-phenylethyl group,

R² means a methyl, isopropyl, cyclopropyl, phenyl or fluorophenyl group and

R³ a 2-methyl-2-propen-1-yl-, 2-chloro-2-propen-1-yl or 3-bromo-2-propenylyl group means a 1-buten-1-yl-, 3-methyl -1-buten-1-yl-, 2-buten-1-yl-, 2-methyl-2-buten-1-yl or 2,3-dimethyl-2-buten-1-yl group, a 2-butyn-1 -yl group, a 1-cyclopenten-1-ylmethyl group or a 2-furanylmethyl group, the tautomers, the enantiomers, the diastereomers, the mixtures thereof, the prodrugs thereof and the salts thereof.

A preferred subgroup of other articles of the present disclosure comprises compounds of general formula I, wherein

R¹ and R² is as defined above and

R³ means a 1-buten-1-yl, 2-buten-1-yl or 2-butyn-1-yl group, the tautomers, enantiomers, diastereomers, mixtures thereof and the salts thereof.

A particularly preferred subgroup of other articles of the present disclosure comprises compounds of the general formula I, wherein

R¹ means a methyl group substituted by a naphthyl, fluoro naphthyl, methyl naphthyl, methoxynaphthyl, (difluoromethoxy) naphthyl, cyano naphthyl or nitronaphthyl group, a methyl group substituted by a 2- (pentafluorophenyl) ethylene group, a methyl group, substituted with a benzofuranyl, methylbenzothiazolyl, quinolinyl, methoxyquinolinyl, isoquinolinyl, methylisoquinolinyl, (difluoromethyl) -isoquinolinyl, (trifluoromethyl) -isoquinolinyl, dimethylisoquinolinyl, (1-cyano-1-methyl-ethyl) isoquinolinyl, phenylisoquinolinyl, methoxyisoquinolinyl, 1,2,3,4-tetrahydrophenanthridinyl, quinazolinyl, methylquinazolinyl, isopropylquinazolinyl, cyclopropylquinazolinyl, phenylquina dimethylamino-quinazolinyl-, pyrrolidin-1-ylquinazolinyl-, piperidin-1-ylquinazolinyl-, piperazin-1-ylquinazolinyl-, morpholin-4-ylquinazolinyl-, ethoxycinnazinyl-quinoline-quinoline-quinoline-quinoline phenylquinoxalinyl, [1,5] naphthyridinyl, [1,6] naphthyridinyl, [1,8] naphthyridinyl or a 1,2-dihydro-1-methyl-2-oxo-quinolinyl group, a phenylcarbonylmethyl group, a phenylcarbonylmethyl group, wherein the phenyl group is substituted with a phenyl group, a phenylcarbonylmethyl group, wherein the phenyl group is substituted with a methoxy, difluoromethoxy, trifluoromethoxy, ethyloxy, isopropyloxy or phenyloxy group, a phenylcarbonylmethyl group in which two is hydrogen, is replaced by an -O-CH 2 -O-, -O-CF 2 -O-, -O-CH 2 -CH 2 -O-, -N (CH₃) -CO-N (CH3) - or a -N (CH3) -CO-O group, a naphthylcarbonylmethyl, indolylcarbonylmethyl or quinolinylcarbonylmethyl group or a 2-cyanimino-2-phenylethyl group,

R² means a methyl, isopropyl, cyclopropyl, phenyl or 4-fluorophenyl group and

R³ means a 1-buten-1-yl, 2-buten-1-yl or a 2-butyn-1-yl group, the tautomers, enantiomers, diastereomers, mixtures thereof and the salts thereof.

Another preferred subgroup of the second article of the present disclosure comprises compounds of the general formula I wherein R¹ and R² is defined as just above and R³ means a 1-butene-1-yl group, the tautomers, enantiomers, diastereomers, mixtures thereof and the salts thereof.

A third preferred subgroup of the second article of the present disclosure comprises compounds of general formula I wherein R¹ and R² is defined as just above and R³ means a 2-butene-1-yl group, the tautomers, enantiomers, diastereomers, mixtures thereof and their salts.

A fourth preferred subgroup of the second article of the present disclosure comprises compounds of general formula I wherein R¹ and R² is defined as just above and R³ means a 2-butyn-1-yl group, the tautomers, enantiomers, diastereomers, mixtures thereof and their salts.

A third article according to the present disclosure relates to compounds of general formula I, wherein

R¹ means a methyl group substituted with a naphthyl, fluoronaphthyl, methylnaphthyl, methoxynaphthyl, (difluoromethoxy) -naphthyl, cyano naphthyl or nitronaphthyl group, a methyl group substituted with a 2- (pentaphiorphenyl) ethenyl group, or a methyl group substituted with a benzofuranyl, methylbenzothiazolyl, quinolinyl, methoxykinolinyl, isoquinolinyl, methylisoquinolinyl, (difluoromethyl) -isoquinolinyl, (trifluoromethyl) -isoquinolinyl, dimethylisoquinolinyl, (1-cyano-1-methyl-ethyl) isoquinolinyl, phenylisoquinolinyl, methoxyisoquinolinyl, 1,2,3,4-tetrahydrophenanthridinyl, quinazolinyl, methylquinazolinyl, isopropylquinazolinyl, cyclopropylquinazolinyl, phenylquina dimethylamino-quinazolinyl-, pyrrolidin-1-ylquinazolinyl-, piperidin-1-ylquinazolinyl-, piperazin-1-ylquinazolinyl-, morpholin-4-ylquinazolinyl-, ethoxycinnazinyl-quinoline-quinoline-quinoline-quinoline phenylquinoxalinyl, [1,5] naphthyridinyl, [1,6] naphthyridinyl, [1,8] naphthyridinyl or a 1,2-dihydro-1-methyl-2-oxo-quinolinyl group,

R² means a methyl, isopropyl, cyclopropyl or phenyl group and

R³ means a 2-chlorobenzyl, 2-bromobenzyl, 2-ethynylbenzyl or 2-cyanobenzyl group, the tautomers, enantiomers, diastereomers, mixtures thereof and their salts.

A first preferred subgroup of the third article of the present disclosure comprises compounds of the general formula I, wherein

R¹ means a (3-methyl-isoquinolin-1-yl) methyl group,

R² means a methyl group and

R³ means a 2-chlorobenzyl, 2-bromobenzyl, 2-ethynylbenzyl or 2-cyanobenzyl group, the tautomers, enantiomers, diastereomers, mixtures thereof and their salts.

A second preferred subgroup of the third article of the present disclosure comprises compounds of the general formula I, wherein R¹ and R² is as defined above and

R³ means a 2-chlorobenzyl group, the tautomers, enantiomers, diastereomers, mixtures thereof and their salts.

A third preferred subgroup of the third article of the present disclosure comprises compounds of the general formula I wherein R¹ and R² are as defined above and R³ means a 2-bromobenzyl group, the tautomers, the enantiomers, the diastereomers, the mixtures thereof and the salts thereof.

A fourth preferred subgroup of the third article of the present disclosure comprises compounds of the general formula I wherein R¹ and R² are as defined above and R³ means a 2-ethynylbenzyl group, the tautomers, enantiomers, diastereomers, mixtures thereof and their salts.

A fifth preferred subgroup of the third article of the present disclosure comprises compounds of the general formula I wherein R¹ and R² are as defined above and R³ means a 2-cyanobenzyl group, the tautomers, enantiomers, diastereomers, mixtures thereof and their salts.

Most particularly preferred are the following compounds of general formula I:

(1) 1 - [(quinazolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((7?) -3-amino-piperidin-1-yl) xanthine, (2) 1- (2- {2 - [(ethylaminocarbonyl) methoxy] phenyl} -2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8 ((7) ?) - 3-Amino-piperidin-1-yl) -xanthine, (3) 1- (2- {2- [(methylaminocarbonyl) methoxy] -phenyl} -2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) 8 - ((7?) -3-amino-piperidin-1-yl) -xanthine, (4) 1- (2-phenyl-2-oxo-ethyl) -3-methyl -7 - ((E) -2-buten-1-yl) -8 - ((7?) - 3-amino-piperidin-1-yl) xanthine, (5) 1 - [(3-methyl-isoquinolin-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((5) -3-amino-piperidinl-yl ) -xanthin, (6) 1 - [(3-methyl-isoquinolin-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino -piperidin-5-yl) -xanthine, (7) 1 - [(4-methyl-isoquinolin-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((5) ) -3-Amino-piperidinl-yl) -xanthine, (8) 1 - [(4-methyl-isoquinolin-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((7?) - 3-amino-piperidin-yl) -xanthine, (9) 1- [2- (2,3-dihydro-benzo [1,4] dioxin-5-yl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8- (3 (7) - amino-piperidin-1-yl) -xanthine, (10) 1 - [(4-methoxy-naphthalen-1-yl) methyl] -3-methyl-7- (2- butyn-1-yl) - 8 - ((5) -3-aminopiperidin-1-yl) -xanthine, (11) 1 - [(4-methoxy-naphthalen-1-yl) methyl] -3-methyl-7 - (2-butyn-1-yl) - 8 - ((5) -3-amino-piperidin-1-yl) -xanthine, (12) 1- [2- (benzo [1,3] dioxol-4-yl) ) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((5) -3-aminopiperidin-1-yl) -xanthine, (13) 1 - [(4-methyl-quinazolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3- (5) -amino-piperidinl-yl) ) -xanthine, (14) 1- (2- {2 - [(isopropylcarbonyl) amino] phenyl} -2-oxo-ethyl) -3-methyl-7 - ((E) -2-butenyl) - 8 - ((5) -3-Amino-piperidin-1-yl) -xanthine, (15) 1- (2- {2 - [(methylaminocarbonyl) methoxy] -phenyl} -2-oxo-ethyl) -3- methyl 7 - ((E) -2-buten1-yl) -8 - ((5) -3-amino-piperidin-1-yl) -xanthine, (16) 1- (2- {2 - [(methylaminocarbonyl) ) methoxy] -phenyl} -2-oxo-ethyl) -3-methyl-7 - ((E) -2-buten-1-yl) -8 - ((S) -3-amino-piperidin-1-yl) - xanthine, (17) 1- (2- {2 - [(Isopropylcarbonyl) amino] -phenyl} -2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -85 ((7?) -3-amino-piperidin-1-yl) -xanthine, (18) 1- (2- {2 - [(isopropylcarbonyl) amino] phenyl} -2-oxo-ethyl) -3-methyl-7 - (( E) -2-Butenyl-8-(- (7β) -3-amino-piperidin-1-yl) -xanthine, (19) 1 - [(4-cyano-naphthalen-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) - 8 - ((R) -3-amino-piperidinl-yl) -xanthine, (20) 1 - [(4-phenyl-quinazolin-2-one) yl) methyl] -3-methyl-7- (2-butyn-l-yl) -8 - ((7?) - 3-amino-piperidin-yl) -xanthine, (21) 1 - [(8-methyl-quinoxalin-6-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((7?) -3-aminopiperidin-1-yl) yl) -xanthin, (22) 1 - [(4-fluoro-naphthalen-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((7?) - 3 -amino-piperidin-120-yl) -xanthine, (23) 1- ((E) -3-pentafluorophenyl-allyl) -3-methyl-7- (2-butyn-1-yl) -8 - ((7? ) -3-Amino-piperidinyl-xanthine, (24) 1 - [(3-trifluoromethyl-isoquinolin-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((7?) - 3-Aminopiperidin-1-yl) -xanthine, (25) 1 - [(3-difluoromethyl-isoquinolin-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((7?) -3-aminopiperidin-1 - yl) -xanthin, (26) 1- [2- (biphenyl-2-yl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((7? ) -3-Amino-piperidinyl-xyl) -xanthine, (27) 1 - [(3-methyl-isoquinolin-1-yl) methyl] -3-cyclopropyl-7- (2-butyn-1-yl) -8 - ((7?) - 3-amino-piperidin-1-yl) -xanthine, (28) 1- [2- (3-methoxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (2) -butyn-1-yl) -8 - ((7β) -3-aminopiperidin-1-yl) -xanthine, (29) 1 - [(3-Methyl-isoquinolin-1-yl) methyl] -3-methyl-7- (2-chloro-benzyl) -8 - ((7?) -3-aminopiperidin-1-yl) -xanthine and (30) 1 - [(3-methyl-isoquinolin-1-yl) methyl] -3-methyl-7- (2-bromo-benzyl) -8 - ((7β) -3-aminopiperidin-1 -yl) -xanthine as well as the tautomers, enantiomers, diastereomers, mixtures thereof and their salts.

According to the specification, the compounds of general formula I are obtained by 20 methods known per se, for example by the following methods:

a) reacting a compound of the general formula

<img file="NO336641B1_D0005.tif" />

where

R¹ to R³ is as defined above and

Z¹ means an leaving group such as a halogen atom such as a chlorine or bromine atom, a substituted hydroxy, mercapto, sulfinyl, sulfonyl or sulfonyloxy group, a methanesulfonyl or methanesulfonyloxy group, with the 3-aminopiperidine, its enantiomers or salts thereof.

It is convenient to carry out the reaction in a solvent such as isopropanol, butanol, tetrahydrofuran, dioxane, dimethylformamide, dimethylsulfoxide, ethylene glycol monomethyl ether, ethylene glycol diethyl ether or sulfolane, optionally in the presence of an inorganic or tertiary organic, e.g. sodium carbonate, potassium carbonate or potassium hydroxide, a tertiary organic base, e.g. triethylamine, or in the presence of N-ethyl diisopropylamine (Hunig base), where these organic bases can simultaneously serve as a solvent, and optionally in the presence of a reaction accelerator such as an alkali metal halide or a palladium-based catalyst, at temperatures between -20 and 180 ° C, but preferably at temperatures between -10 and 120 ° C. However, the reaction can also be carried out without solvent or with excess 3-aminopiperidine.

b) deprotecting a compound of the general formula

<img file="NO336641B1_D0006.tif" />

(III), wherein R¹, R² and R³ is as defined above.

In accordance with the present invention, the tert-butyloxycarbonyl group is cleaved by treatment with an acid such as trifluoroacetic acid or hydrochloric acid, or by treatment with bromotrimethylsilane or iotrimethylsilane, optionally using a solvent such as methylene chloride, ethyl acetate, dioxopropyl, dioxane, between 0 and 80 ° C.

c) To prepare a compound of general formula I, wherein R¹ According to the above definition, a carboxy group contains:

deprotection of a compound of the general formula

<img file="NO336641B1_D0007.tif" />

(iv) wherein R² and R³ are as defined above and R¹ contains a carboxy group protected by a C 1-4 alkyl group.

The protecting group is cleaved by hydrolysis, for example using an acid such as hydrochloric or sulfuric acid, or an alkali metal hydroxide such as lithium hydroxide, sodium hydroxide or potassium hydroxide, in a solvent such as methanol, ethanol, isopropanol, tetrahydrofuran or dioxane in the presence of water.

In the reactions described above, any reactive groups present, such as carboxy, amino, alkylamino or imino groups, can be protected during the reaction with conventional protecting groups which are decomposed after the reaction.

For example, a protecting group for a carboxy group may be a trimethylsilyl, methyl, ethyl, tert-butyl, benzyl or tetrahydropyranyl group and protecting groups for an amino, alkylamino or imino group may be a formyl, acetyl, trifluoroacetyl , ethoxycarbonyl, tert-butoxycarbonyl, benzyloxycarbonyl, benzyl, methoxybenzyl or 2,4-dimethoxybenzyl group, and for the amino group also a phthalyl group.

Any protecting group used is then optionally cleaved, for example, by hydrolysis in an aqueous solvent, e.g. in water, isopropanol / water, acetic acid / water, tetrahydrofuran / water or dioxane / water, in the presence of an acid such as trifluoroacetic acid, hydrochloric acid or sulfuric acid, or in the presence of an alkali metal base such as sodium hydroxide or potassium hydroxide, or aprotic, f instance. in the presence of iodine trimethylsilane, at temperatures between 0 and 120 ° C, preferably at temperatures between 10 and 100 ° C.

However, a benzyl, methoxybenzyl or benzyloxycarbonyl group is cleaved, for example, hydrogenolytic, e.g. with hydrogen in the presence of a catalyst such as palladium / charcoal, in a suitable solvent such as methanol, ethanol, ethyl acetate or glacial acetic acid, optionally by the addition of an acid such as hydrochloric acid, at temperatures between 0 and 100 ° C, but preferably at temperatures between 20 and 60 ° C, and at a hydrogen pressure of 1 to 7 bar, but preferably 3 to 5 bar. However, a 2,4-dimethoxybenzyl group is preferably cleaved in trifluoroacetic acid in the presence of anisole.

A tert-butyl or tert-butyloxycarbonyl group is preferably cleaved by treatment with an acid such as trifluoroacetic acid or hydrochloric acid, or by treatment with iodine trimethylsilane, optionally using a solvent such as methylene chloride, dioxane, methanol or diethyl ether.

A trifluoroacetyl group is preferably cleaved by treatment with an acid such as hydrochloric acid, optionally in the presence of a solvent such as acetic acid, at temperatures between 50 and 120 ° C, or by treatment with sodium hydroxide solution, optionally in the presence of a solvent such as tetrahydrofuran , at temperatures between 0 and 50 ° C.

A phthalyl group is preferably cleaved in the presence of hydrazine or a primary amine such as methylamine, ethylamine or n-butylamine, in a solvent such as methanol, ethanol, isopropanol, toluene / water or dioxane, at temperatures between 20 and 50 ° C.

Furthermore, the compounds of the general formula I obtained can be cleaved to their enantiomers and / or diastereomers, as mentioned above. Accordingly, for example, cis / trans mixtures can be cleaved to their cis and trans isomers, and compounds having at least one optically active carbon atom can be separated into their enantiomers.

Accordingly, for example, cis / trans mixtures can be cleaved by chromatography to cis and trans isomers thereof, the compounds of the general formula I present as racemates can be separated by methods known per se (cf. Allinger NL and Eliel EL in Topics in Stereochemistry, vol. 6, Wiley Interscience, 1971) to their optical antipodes, and compounds of general formula I having at least 2 asymmetric carbon atoms can be cleaved to their diastereomers on the basis of their physicochemical differences, using methods known per se, eg. by chromatography and / or fractional crystallization, and if these compounds are obtained in racemic form, they can then be cleaved to the enantiomers mentioned above.

The enantiomers are preferably separated by column separation on chiral phases or by recrystallization from an optically active solvent or by reaction with an optically active substance which forms salts or derivatives, such as e.g. esters or amides, with the racemic compound, especially acids and the activated derivatives or alcohols thereof, and by separating the diastereomeric mixture of salts or derivatives thus obtained, e.g. on the basis of their different solubility, while the free antipodes can be released from the pure diastereomeric salts or derivatives by suitable means. Commonly used optically active acids are e.g. The D and L forms of tartaric or dibenzoyltartaric, di-o-tolyltartaric, malic, mandelic, camphorsulfonic, glutamic, aspartic or quinic. For example, an optically active alcohol may be (+) or (-) - menthol, and an optically active acyl group in amides may be, for example, a (+) or (-) - mentyloxycarbonyl.

Furthermore, the compounds of formula I can be converted to the salts thereof, for pharmaceutical use especially to the physiologically acceptable salts with inorganic or organic acids. Acids which can be used for this purpose include, for example, hydrochloric, bromohydric, sulfuric, phosphoric, fumaric, succinic, lactic, citric, tartaric or maleic acids.

If the novel compounds of formula I so obtained further contain a carboxy group, they may then, if desired, be converted to the salts thereof with inorganic or organic bases, for pharmaceutical use especially to the physiologically acceptable salts thereof. Suitable bases for this purpose include, for example, sodium hydroxide, potassium hydroxide, arginine, cyclohexylamine, ethanolamine, diethanolamine and triethanolamine.

The compounds of general formulas II to IV, which are used as starting materials, are either known from the literature or can be obtained by methods known from the literature (cf. Examples I to LXXI).

As already mentioned above, the compounds of the general formula I as described and the physiologically acceptable salts thereof have valuable pharmacological properties, especially an inhibitory effect on the enzyme DPP-IV.

The biological properties of the new compounds were investigated as follows:

The ability of the substances and their corresponding salts to inhibit DPP-IV activity can be demonstrated in a test setup in which an extract of the human colon carcinoma cell line Caco-2 is used as the DPP-IV source. Differentiation of cells to induce DPP336641

IV expression, was performed as described by Reiher et al. in the article Increased expression of intestinal cell line Caco-2, which was printed in Proc. Natl. Acad. Sci., Vol. 90, pp. 57575761 (1993). The cell extract was obtained from cells solubilized in a buffer (10mM Tris HCl, 0 .15 M NaCl, 0.04 µl Kirsti aprotinin, 0.5% Nonidet-P40, pH 8.0) by centrifuging at 35,000 g for 30 minutes. at 4 ° C (to remove cell debris).

The DPP-IV assay was performed as follows:

μΐ substrate solution (AFC; AFC is amido-4-trifluoromethyl coumarin), total concentration

100 µΜ, were placed in black microtiter plates. 20 μΐ assay buffer (total concentrations 50 mM Tris HCl pH 7.8, 50 mM NaCl, 1% DMSO) was pipetted in. The reaction was started by addition of 30 μΐ solubilized Caco-2 protein (final concentration 0.14 pg protein per ml). well). The test substances to be tested were typically diluted in advance at 20 μΐ, and the volume of the assay buffer was similarly reduced. The reaction was carried out at ambient temperature and incubated for 60 minutes. Then, the fluorescence was measured in a Victor 1420 Multilabel Counter, where the excitation wavelength was 405 nm and the emission wavelength was 535 nm. Blank readings (equivalent to 0% activity) were obtained in mixtures without any Caco-2 protein (volume replaced by assay buffer), control values ​​(equivalent to 100% activity) were obtained in mixtures without added substance. The strength of the test substances in question, expressed as IC 50 values, was calculated from dose / activity curves, which in each case consisted of 11 measurement points. The following results were achieved:

<td>Connection (Example #)</td><td>DPP-IV inhibition IC50 [nM]</td>

<td> 2(3)</td><td> 2160</td>

<td> 2(9)</td><td> 264</td>

<td> 2(12)</td><td> 16</td>

<td> 2(17)</td><td> 32</td>

<td> 2(20)</td><td> 12</td>

<td> 2(25)</td><td> 4</td>

<td> 2(27)</td><td> 9</td>

<td> 2(35)</td><td> 5</td>

<td> 2(37)</td><td> 5</td>

<td> 2(43)</td><td> 6</td>

<td> 2(51)</td><td> 6</td>

<td> 2(52)</td><td> 9</td>

<td> 2(59)</td><td> 250</td>

<td> 2(66)</td><td> 22</td>

<td> 2(80)</td><td> 1</td>

<td> 2(86)</td><td> 2</td>

<td> 2(96)</td><td> 2</td>

<td> 2(99)</td><td> 1</td>

<td> 2(100)</td><td> 3</td>

<td> 2(108)</td><td> 3</td>

<td> 2(129)</td><td> 3</td>

<td> 2(130)</td><td> 3</td>

<td> 2(131)</td><td> 3</td>

<td> 2(132)</td><td> 1</td>

<td> 2(135)</td><td> 3</td>

<td> 2(137)</td><td> 13</td>

<td> 2(138)</td><td> 8</td>

<td> 2(139)</td><td> 4</td>

<td> 2(142)</td><td> 1</td>

<td> 2(145)</td><td> 4</td>

<td> 2(148)</td><td> 1</td>

<td> 2(150)</td><td> 1</td>

<td> 2(151)</td><td> 3</td>

<td> 2(152)</td><td> 4</td>

<td> 2(185)</td><td> 3</td>

<td> 2(217)</td><td> 4</td>

<td> 2(247)</td><td> 2</td>

<td> 2(251)</td><td> 12</td>

<td> 2(256)</td><td> 8</td>

<td> 2(260)</td><td> 13</td>

<td> 2(264)</td><td> 6</td>

<td> 2(277)</td><td> 6</td>

<td> 2(280)</td><td> 5</td>

<td> 2(285)</td><td> 3</td>

<td> 2(287)</td><td> 11</td>

<td> 2(288)</td><td> 14</td>

The compounds prepared according to the specification are well tolerated, such as when 10 mg / kg of the compound of Example 2 (80) was administered orally to rats, no changes in animal behavior could be detected.

In view of their ability to inhibit DPP-IV activity, the compounds of the general formula I as described and the corresponding pharmaceutically acceptable salts thereof are suitable for the treatment of all the conditions or diseases which may be affected by inhibition of DPP-IV. -Activity. Therefore, it is expected that the compounds of the specification will be suitable for the prevention or treatment of diseases or conditions such as type 1 and type 2 diabetes mellitus, diabetic complications (such as e.g. retinopathy, nephropathy or neuropathy), metabolic acidosis or ketosis, reactive hypoglycemia, insulin resistance, metabolic syndrome, dyslipidemia of various origins, arthritis, atherosclerosis and related diseases, obesity, allograft transplantation, and calcitonin-induced osteoporosis. Furthermore, these substances can prevent B-cell degeneration such as e.g. apoptosis or necrosis of B cells in the pancreas. The substances are also suitable for improving or restoring the function of pancreatic cells and also increasing the number and size of B336641 cells in the pancreas. In addition, and on the basis of the role of glucagon-like peptides, e.g. GLP-1 and GLP-2 and their link to DPP-IV inhibition, it is likely that the compounds of the specification are suitable for achieving e.g. a sedative or anxiety-relieving effect and that they also advantageously affect catabolic conditions after surgery or hormonal stress responses or reduce mortality or disease after myocardial infarction. They are also suitable for treating all conditions associated with the above effects and which are mediated by GLP-1 or GLP-2. The compounds of the specification can also be used as diuretics or antihypertensives and are suitable for the prevention and treatment of acute renal failure. Furthermore, the compounds of the specification can be used to treat inflammatory diseases of the respiratory tract. They are also suitable for the prevention and treatment of chronic inflammatory bowel diseases such as irritable bowel syndrome (IBS), Crohn's disease or ulcerative colitis and also pancreatitis. They are also likely to be used for all types of gastrointestinal damage or impairment, such as colitis and enteritis. It is also expected that DPP-IV inhibitors and, consequently, also compounds of the descriptive nature, can be used to treat sterility or to improve fertility in humans or mammals, especially when sterility is related to insulin resistance or polycystic ovarian syndrome. On the other hand, these substances are suitable for affecting sperm motility and can therefore be used as contraceptives for men. The substances are also suitable for the treatment of growth hormone deficiency which is related to reduced height growth, and can advantageously also be used for all indications where growth hormone can be used. The compounds of the specification, on the basis of their inhibitory effect on DPP-IV, are also suitable for the treatment of various autoimmune diseases such as e.g. rheumatoid arthritis, multiple sclerosis, thyroiditis and Basedow's disease etc. They can also be used to treat viral diseases and also to stimulate blood production, for example in HIV infections, in benign prostatic hyperplasia, gingivitis, as well as in the treatment of neuronal defects and neurodegenerative diseases such as for example, Alzheimer's disease. The described compounds may also be used for the treatment of tumors, especially for modifying tumor invasion and also metastasis; Examples here are their use in the treatment of T-cell lymphomas, acute lymphoblastic leukemia, cell-based pancreatic carcinomas, basal cell carcinomas, or breast cancer. Other indications are stroke, ischemia of different origins, Parkinson's disease and migraine. In addition, further indications include follicular and epidermal hyperkeratosis, increased keratinocyte proliferation, psoriasis, encephalomyelitis, glomerulonephritis, lipodystrophies, as well as psychosomatic, depressive and neuropsychiatric diseases of all types.

The compounds of the specification can also be used with other active substances. Therapeutic agents suitable for such combinations include, for example, antidiabetic agents such as metformin, sulfonylurea compounds (e.g., glibenclamide, tolbutamide, glimepiride), nateglinide, repaglinide, thiazolidinedione (e.g., rosiglitazone, pioglitazone), PPAR gamma agonists (e.g. GI 262570) and antagonists, PPARgamma / alpha modulators (e.g. KRP 297), alpha-glucosidase inhibitors (e.g. acarbose, voglibose), other DPPIV inhibitors, alpha2 antagonists, insulin and insulin analogues, GLP1 and GLP-1 analogs (eg exendin-4) or amylin. Also, SGLT2 inhibitors such as ΤΙ 095, inhibitors of protein tyrosine phosphatase 1, substances that affect the down-regulation of glucose production in the liver, such as inhibitors of glucose-6-phosphatase or fructose-1,6-bisphosphatase, glycogen phosphorylase, glucagon receptor antagonists and inhibitors of phospholene pyruvate carboxykinase, glycogen synthase kinase or pyruvate dehydrokinase, lipid lowering agent, lipid lowering , atorvastatin), fibrates (e.g., bezafibrate, fenofibrate), nicotinic acid and derivatives thereof, PPAR alpha agonists, PPAR delta agonists, ACAT inhibitors (e.g. avasimibe) or cholesterol resorption inhibitors such as ezetimibe, bile acid-binding substances such as cholestyramine, inhibitors of ileal bile acid transport, HDL-increasing compounds such as inhibitors of CETP or regulators of ABC1 or active substances for the treatment of obesity, such as f. ex. sibutramine or tetrahydrolipostatin, dexfenfluramine, axokine, cannabinoid 1 receptor antagonists, MCH-1 receptor antagonists, MC4 receptor agonists, NPY5 or NPY2 antagonists or B3 agonists such as SB-418790 or AD-9677 agonists of the 5HT2c receptor.

It is also possible to combine the compounds with drugs for the treatment of high blood pressure, such as e.g. ΑΠ antagonists or ACE inhibitors, diuretics, B-blockers, Caantagonists, etc., or combinations thereof.

The dose required to achieve such an effect, administered intravenously, is suitably 1 to 100 mg, preferably 1 to 30 mg, and administered orally, 1 to 1000 mg, preferably 1 to 100 mg, in each case 1 to 4 times per day. . day. For this purpose, the compounds of formula I according to the invention, optionally combined with other active substances, are incorporated together with one or more inert, conventional carriers and / or diluents, e.g. corn starch, lactose, glucose, microcrystalline cellulose, magnesium stearate, polyvinylpyrrolidone, citric acid, tartaric acid, water, water / ethanol, water / glycerol, water / sorbitol, water / polyethylene glycol, propylene glycol, cetyl stearyl alcohol, carboxymethylcellulose such as , in conventional galenic preparations such as single or coated tablets, capsules, powders, suspensions or suppositories.

The following examples are intended to illustrate the description:

Preparation of the starting compounds:

Example I

1,3-dimethyl-7- (2,6-dicvano-benzyl) -8-bromo-xanthine

A mixture of 555 mg of 8-bromo-theophylline and 0.39 ml of pure base in 9 ml of N, N-dimethyl-20-formamide is combined with 600 mg of 2-bromomethyl-isophthalonitrile and stirred overnight at ambient temperature. For working up, the reaction mixture is poured into water. The formed precipitate is suction filtered, washed with water and dried.

Yield: 686 mg (83% of theoretical value)

Rf value: 0.56 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 399, 401 [M + H]⁺

The following compounds are obtained analogously to Example I:

(1) 3-methyl-7- (3-methyl-2-buten-1-yl) -8-chloro-xanthine

Mass Spectrum (ESI⁺): m / z = 269, 271 [M + H]⁺ (2) 3-methyl-7- (2-cyano-benzyl) -8-chloro-xanthine

Mass Spectrum (ESI⁺): m / z = 316, 318 [M + H]⁺ (3) 1- (2-Phenyl-2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8-bromo-xanthine Mass Spectrum (ESI)⁺): m / z = 415, 417 [M + H]⁺ (4) 3-methyl-7 - [(2-trimethylsilanyl-ethoxy) methyl] -8-bromo-xanthine (Performed in the presence of potassium carbonate)

Mass Spectrum (ESI⁺): m / z = 375, 377 [M + H]⁺ (5) 3-Methyl-7- (3-methyl-2-buten-1-yl) -8-bromo-xanthine

Mass Spectrum (ESI⁺): m / z = 313, 315 [M + H]⁺ (6) 3-methyl-7- (2,3-dimethyl-2-buten-1-yl) -8-bromo-xanthine Rf value: 0.43 (silica gel, methylene chloride / methanol = 9: 1) Mass spectrum ( ESI⁺): m / z = 327, 329 [M + H]⁺ (7) 3-Methyl-7- (2-butyn-1-yl) -8-bromo-xanthine

Rf value: 0.72 (silica gel, ethyl acetate)

Mass Spectrum (ESI⁺): m / z = 297/299 [M + H]⁺ (8) 3-Methyl-7 - ((E) -2-buten-1-yl) -8-bromo-xanthine (The product is contaminated with about 10-20% Z compound)

Rf value: 0.55 (silica gel, cyclohexane / ethyl acetate / methanol = 6: 3: 1) Mass spectrum (ESI⁺): m / z = 299, 301 [M + H]⁺ (9) 3-Methyl-7 - [(1-cyclopenten-1-yl) methyl] -8-bromo-xanthine Mass Spectrum (ESI⁺): m / z = 325, 327 [M + H]⁺ (10) 1- (2-Phenyl-2-oxo-ethyl) -3-methyl-7 - [(1-cyclopenten-1-yl) methyl] -8-bromo-xanthine Mass Spectrum (ESI)⁺): m / z = 443, 445 [M + H]⁺ (11) 1- (2-Phenyl-2-oxo-ethyl) -3-methyl-7 - ((E) -2-buten-1-yl) -8-bromo-xanthine (the product contains about 25% Z isomer)

Mass Spectrum (ESI⁺): m / z = 417, 419 [M + H]⁺ (12) 1- (2-Phenyl-2-oxo-ethyl) -3-methyl-7- (2-methyl-allyl) -8-bromo-xanthine

Rf value: 0.71 (silica gel, methylene chloride / methanol - 95: 5)

Mass Spectrum (ESI⁺): m / z = 417, 419 [M + H]⁺ (13) 1- (2-Phenyl-2-oxo-ethyl) -3-methyl-7- (3-bromo-allyl) -8-bromo-xanthine

Rf value: 0.68 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 481, 483, 485 [M + H]⁺ (14) 1- (2-Phenyl-2-oxo-ethyl) -3-methyl-7 - [(furan-2-yl) methyl] -8-bromo-xanthine Rf value: 0.60 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 443, 445 [M + H]⁺ (15) 1- (2-Phenyl-2-oxo-ethyl) -3-methyl-7- (2-chloro-allyl) -8-bromo-xanthine

Rf value: 0.77 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 437, 439, 441 [M + H]⁺ (16) 1- (2-Phenyl-2-oxo-ethyl) -3-methyl-7 - ((Z) -2-methyl-2-buten-1-yl) -8-bromo-xanthine Rf 0.77 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 431, 433 [M + H]⁺ (17) 1- (2-Phenyl-2-oxo-ethyl) -3-methyl-7 - ((E) -2-methyl-2-buten-1-yl) -8-bromo-xanthine Rf 0.77 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 431, 433 [M + H]⁺ (18) 1- (2-phenyl-2-oxo-ethyl) -3-methyl-7- (1-phenylsulfanyl-butyl) -8-bromo-xanthine Rf value: 0.83 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 527, 529 [M + H]⁺ (19) 3-methyl-7- (3-methyl-1-phenylsulfanyl-butyl) -8-bromo-xanthine ([(1-chloro-3-methyl-butyl) sulfanyl] -benzene) is used as the starting material for the reaction, obtained by chlorination of [(3-methyl-butyl) sulfanyl] -benzene with N-chloro-succinimide in carbon tetrachloride)

Rf value: 0.38 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 423, 425 [M + H]⁺ (20) 1,3-Dimethyl-7- (2-bromo-benzyl) -8-chloro-xanthine

Rf value: 0.50 (silica gel, cyclohexane / ethyl acetate = 1: 1) (21) 1,3-dimethyl-7- (2-chloro-benzyl) -8-chloro-xanthine

Rf value: 0.50 (silica gel, cyclohexane / ethyl acetate = 1: 1) (22) 3-cyclopropyl-7- (2-butyn-1-yl) -8-bromo-xanthine

Rf value: 0.45 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 1)

Mass Spectrum (ESI⁺): m / z = 223/225 [M + H]⁺

Example II 1- (2- {2 - [(Ethoxycarbonyl) methoxy] -phenyl} -2-oxo-ethyl) -3-methyl-7- (3-methyl-2-buten-1-yl) 8-3 - (tert-butyloxycarbonylamino) -piperidine-1-xanthine mg ethyl bromoacetate is added to a mixture of 200 mg of 1- [2- (2-hydroxy-phenyl) -2-oxoethyl] -3-methyl-7- ( 3-methyl-2-buten-1-yl) -8 - [3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine and 63 mg of potassium carbonate in 3 ml of Ν, Ν-dimethylformamide. The reaction mixture is stirred for five hours at ambient temperature. For working up, it is combined with water and the resulting precipitate is suction filtered, washed with water and dried for three hours at 80 ° C in a drying cabinet.

Yield: 216 mg (94% of theoretical value)

Mass Spectrum (ESI⁺): m / z = 653 [M + H]⁺

The following compounds are obtained analogously to Example Π:

(1) 1- (2- {2 - [(aminocarbonyl) methoxy] -phenyl} -2-oxo-ethyl) -3-methyl-7- (3-methyl-2-butenyl) -8- [3 - (tert-butyloxycarbonylamino) -piperidin-l-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 624 [M + H]⁺ (2) 1- (2- {3 - [(methylsulfanyl) methoxy] phenyl} -2-oxo-ethyl) -3-methyl-7- (3-methyl-2-butenyl) -8- [3 - (tert-butyloxycarbonylamino) -piperidin-l-yl] -xanthine

Rf value: 0.20 (silica gel, cyclohexane / ethyl acetate - 6: 4)

Mass Spectrum (ESI⁺): m / z - 627 [M + H]⁺ (3) 1- (2- {3 - [(Ethoxycarbonyl) methoxy] -phenyl} -2-oxo-ethyl) -3-methyl-7- (3-methyl-2-butenyl) -8- [3 - (tert-butyloxycarbonylamino) -piperidin-l-yl] -xanthine

Rf value: 0.50 (silica gel, cyclohexane / ethyl acetate = 3: 7) (4) 1- (2- {2 - [(methylaminocarbonyl) methoxy] phenyl} -2-oxo-ethyl) -3-methyl 7- (3-methyl-2butene-1-yl) - 8- [3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine Mass Spectrum (ESI⁺): m / z = 638 [M + H]⁺ (5) 1- (2- {2 - [(Dimethylaminocarbonyl) methoxy] phenyl} -2-oxoethyl) -3-methyl-7- (3-methyl-2butene-1-yl) - 8- [3 - (tert-Butyloxycarbonylamino) -piperidin-1-yl] -xanthine Mass Spectrum (ESI⁺): m / z = 652 [M + H]⁺ (6) 1- (2- {3 - [(methoxycarbonyl) methoxy] -phenyl} -2-oxo-ethyl) -3-methyl-7- (3-methyl-2-butene-1-yl) -8- [ 3- (tert-Butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 639 [M + H]⁺ (7) 1- (2- {2 - [(Ethylaminocarbonyl) methoxy] phenyl} -2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8 [(7?) -3 - (tert -butyl oxycarbonylamino) -piperidin-1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 636 [M + H]⁺ (8) 1- (2- {2- [(methylaminocarbonyl) methoxy] -phenyl} -2-oxo-ethyl) -3-methyl-7 - [(1-cyclopenten-1-yl) methyl] -8- [3 - (tert-Butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 650 [M + H]⁺ (9) 1- (2- {2- [(methylaminocarbonyl) methoxy] phenyl} -2-oxoethyl) -3-methyl-7- (2-butyn-1-yl) 8- [3- (tert) -butyloksykarbonylamino) -piperidin-l-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 622 [M + H]⁺ (10) 1- (2- {2 - [(aminocarbonyl) methoxy] -phenyl} -2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8 [3- (tert) (butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z - 608 [M + H]⁺ (11) 1- (2- {2 - [(methoxycarbonyl) methoxy] phenyl} -2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8 [3- (tert) (butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 623 [M + H]⁺ (12) 1- (2- {2- [(isopropyloxycarbonyl) methoxy] -phenyl} -2-oxo-ethyl) -3-methyl 1-7- (3-methyl-2-buten-1-yl) - 8 - [3- (tert-Butyloxycarbonylamino) -piperidin-1-yl] -xanthine Mass Spectrum (ESI⁺): m / z - 667 [M + H]⁺ (13) 1- (2- {2 - [(methylaminocarbonyl) methoxy] -phenyl} -2-oxo-ethyl) -3-methyl-7- (2-butyn-120-yl) -8 - [(7?) -3- (tert-butyloxycarbonylamino) -piperidin-l-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 622 [M + H]⁺ (14) 1- (2- {2 - [(methylaminocarbonyl) methoxy] -phenyl} -2-oxo-ethyl) -3-methyl-7 - ((E) -2-buten1-yl) -8- [3 - (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine (the product contains some Z-isomer)

Rf value: 0.35 (silica gel, cyclohexane / ethyl acetate / methanol = 5: 4: 1)

Mass Spectrum (ESI⁺): m / z = 624 [M + H]⁺ (15) 1- (2- {2 - [(ethylaminocarbonyl) methoxy] phenyl} -2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) 8 - [(S) -3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 636 [M + H]⁺ (16) 1- (2- {2 - [(methylaminocarbonyl) methoxy] phenyl} -2-oxoethyl) -3-methyl-7- (2-butynyl) -8 - [(5) -3 - (tert-butyloxycarbonylamino) -piperidin-l-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 622 [M + H]⁺ (17) 1- (2- {2 - [(methoxycarbonyl) methoxy] phenyl} -2-oxo-ethyl) -3-methyl-7- (3-methyl-2butene-1-yl) - 8- [3 - (tert-Butyloxycarbonylamino) -piperidin-1-yl] -xanthine Mass Spectrum (ESI⁺): m / z = 639 [M + H]⁺ (18) 1- (2- {2 - [(methylaminocarbonyl) methoxy] phenyl} -2-oxo-ethyl) -3-methyl-7- (3-methyl-210-buten-1-yl) - 8- [ (5) -3 - (tert-Butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 638 [M + H]⁺ (19) 2- (2-Acetyl-phenoxy) -2V-ethyl-acetamide Mass Spectrum (ESI⁺): m / z = 222 [M + H]⁺ (20) 1- {2- [2- (1-methoxycarbonyl-ethoxy) -phenyl] -2-oxo-ethyl} -3-methyl-7- (2-butyn-1-yl) -8 [3- tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 637 [M + H]⁺ (21) 1- {2- [2- (1-Aminocarbonyl-ethoxy) -phenyl] -2-oxo-ethyl} -3-methyl-7- (2-butyn-1-yl) -8- [3 ( tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine Mass Spectrum (ESI⁺): m / z = 622 [M + H]⁺ (22) 2- (2-Acetyl-phenoxy) -7V-methyl-acetamide

Mass Spectrum (ESI⁺): m / z = 208 [M + H]⁺ (23) 1- {2- [2- (2-oxo-propoxy) -phenyl] -2-oxo-ethyl} -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 607 [M + H]⁺ (24) 1- {2- [2- (1-Ethoxycarbonyl-1-methyl-ethoxy) -phenyl] -2-oxo-ethyl} -3-methyl-7- (2-butynyl) -8- [ 3- (tert-butyloxycarbonylamino) -piperidin-l-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 665 [M + H]⁺ (25) 1- {2- [2-Cyanomethoxy-phenyl] -2-oxo-ethyl} -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidine -1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 590 [M + H]⁺ (26) 1- (2- {2 - [(methylsulfanyl) methoxy] phenyl} -2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8- [3 (tert) -butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 611 [M + H]⁺ (27) 1- {[2- (tert -butylcarbonyl) -benzofuran-3-yl] methyl} -3-methyl-7- (2-butyn-1-yl) - 8- [3 (tert-butyloxycarbonylamino) ) -piperidin-1-yl] -xanthine (Formed as the main product when 1- [2- (2-hydroxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-butynl-yl) -8 - [3- (tert-Butyloxycarbonylamino) -piperidin-1-yl] -xanthine is reacted with 1-chloro3,3-dimethyl-butan-2-one)

Mass Spectrum (ESI⁺): m / z = 631 [M + H]⁺

Example 1- 1- [2- (2-hydroxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

1.30 g of 3-tert-butyloxycarbonylamino-piperidine is added to a mixture of 2.51 g of 1- [2- (2hydroxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl) 2-buten-1-yl) -8-chloro-xanthine and 880 mg of sodium carbonate in 8 ml of dimethyl sulfoxide. The reaction mixture is stirred for 18 hours at 60 ° C. For working up it is combined with water and the formed precipitate is suction filtered. The solid crude product is dissolved in ethyl acetate, the solution is dried over magnesium sulfate and evaporated. The flask residue is chromatographed through a silica gel column with cyclohexane / ethyl acetate (10: 1 to 1: 1) as the eluent.

Yield: 2.56 g (91% of theoretical value)

Mass Spectrum (ESI⁺): m / z = 567 [M + H]⁺

The following compounds are obtained analogously to Example ΙΠ:

(1) 3-Methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidin-1-yl] xanthine

Mass Spectrum (ESI⁺): m / z = 433 [M + H]⁺ (2) 1- (1-Methyl-2-oxo-2-phenyl-ethyl) -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z - 565 [M + H]⁺ (3) 3-Methyl-7- (2-cyano-benzyl) - 8- [3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine Rf value: 0.90 (silica gel, methylene chloride / methanol = 9: 1)

Mass Spectrum (ESI '): m / z = 478 [MH]' (4) -1-methyl-3 - [(methoxycarbonyl) methyl] -7- (2-cyano-benzyl) -8- [3- (tert-butyloxycarbonylamino) ) -piperidin-1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z - 552 [M + H]⁺ (5) 1-Methyl-3-cyanomethyl-7- (2-cyano-benzyl) -8- [3- (tert-butyloxycarbonylamino) piperidin-1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 519 [M + H]⁺ (6) 1-Methyl-3- (2-propyn-1-yl) -7- (2-cyano-benzyl) -8- [3- (tert-butyloxycarbonylamino) piperidin-1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 518 [M + H]⁺ (7) 1- [2- (3-Nitro-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butyloxycarbonyl) lamino) -piperidin-1-yl] -xanthine

Rf value: 0.25 (silica gel, cyclohexane / ethyl acetate / methanol = 7: 2: 1)

Mass Spectrum (ESI⁺): m / z = 596 [M + H]⁺ (8) 1-Methyl-3- (2-propen-1-yl) -7- (2-cyano-benzyl) -8- [3- (tert-butyloxycarbonylamino) piperidin-1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 520 [M + H]⁺ (9) 1- (2-Phenyl-2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) piperidin-1-yl] - xanthine

Mass Spectrum (ESI⁺): m / z = 535 [M + H]⁺ (10) 1- [2- (2-nitro-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butyloxycarbonyl) lamino) -piperidin-1-yl] -xanthine

Rf value: 0.52 (silica gel, cyclohexane / ethyl acetate = 3: 7)

Mass Spectrum (ESI⁺): m / z = 596 [M + H]⁺ (11) 1-Methyl-3-phenyl-7- (2-cyano-benzyl) -8- [3- (tert-butyloxycarbonylamino) -piperidinyl] xanthine

Mass Spectrum (ESI⁺): m / z = 556 [M + H]⁺ (12) 1- [2- (2-nitro-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8 - [(5) - 3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 596 [M + H]⁺ (13) 1 - [(Cinnolin-4-yl) methyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidine-1 -yl] -xanthine mixed with 1 - [(1,4-dihydro-cinnolin-4-yl) methyl] 3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidin-l-yl] xanthine

Rf value: 0.62 (silica gel, ethyl acetate) (14) 1- ({4-oxo-3 - [(2-trimethylsilanyl-ethoxy) methyl] -3,4-dihydro-phthalazin-1-yl} methyl ) -3-methyl-7- (3-methyl-2-buten-1-yl) - 8- [3- (tert-butyl oxycarbonylamino) -piperidin-1-yl] -xanthine (Performed with potassium carbonate in the presence of Hinig base )

Rf value: 0.27 (silica gel, cyclohexane / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z = 720 [M + H]⁺ (15) 1- [(isoquinolin-3-yl) methyl] -3-methyl-7- (3-methyl-2-buten-1-yl) - 8 - [3- (tert-butyloxycarbonylamino) -piperidine 1-yl] -xanthine

Rf value: 0.31 (silica gel, ethyl acetate / petroleum ether = 7: 3)

Mass Spectrum (ESI⁺): m / z = 574 [M + H]⁺ (16) 1 - [(3-methyl-4-oxo-3,4-dihydro-phthalazin-1-yl) methyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8 - [3- (tert-butyloxycarbonylamino) -piperidin-l-yl] -xanthine

Rf value: 0.45 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 95: 5) Mass spectrum (ESI⁺): m / z = 605 [M + H]⁺ (17) 3-Methyl-7- (2,3-dimethyl-2-buten-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidinyl] xanthine (Performed with potassium carbonate)

Rf value: 0.42 (silica gel, methylene chloride / methanol = 20: 1)

Mass Spectrum (ESI⁺): m / z = 447 [M + H]⁺ (18) 3-Methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine (Performed with potassium carbonate)

Melting point: 235-237 ° C

Mass Spectrum (ESI⁺): m / z = 417 [M + H]⁺ (19) 1 - [(Quinolin-4-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) piperidin-1-yl] -xanthine (Made with potassium carbonate)

Rf value: 0.36 (silica gel, ethyl acetate)

Mass Spectrum (ESI⁺): m / z = 558 [M + H]⁺ (20) 1 - [(isoquinolin-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyl oxycarbonylamino) -piperidin-1-yl] -xanthine (Made with potassium carbonate)

Rf value: 0.71 (silica gel, ethyl acetate)

Mass Spectrum (ESI⁺): m / z = 558 [M + H]⁺ (21) 1 - [(isoquinolin-1-yl) methyl] -3-methyl-7 - ((E) -2-buten-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidine-1 -yl] -xanthine (Made with potassium carbonate; the product contains about 20% Z-isomer)

Rf value: 0.24 (silica gel, ethyl acetate / petroleum ether = 1: 1)

Mass Spectrum (ESI⁺): m / z = 560 [M + H]⁺ (22) 3-Methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert-butyloxycarbonylamino) -piperidin-1-yl] xanthine (Performed with potassium carbonate)

Rf value: 0.64 (silica gel, ethyl acetate)

Mass Spectrum (ESI⁺): m / z = 417 [M + H]⁺ (23) 3-Methyl-7- (2-butyn-1-yl) -8 - [(5) -3- (tert-butyloxycarbonylamino) -piperidin-1-yl] xanthine (Potassium carbonate)

Rf value: 0.64 (silica gel, ethyl acetate)

Mass Spectrum (ESI⁺): m / z = 417 [M + H]⁺ (24) 3-methyl-7 - ((E) -2-buten-1-yl) -8 - [(5) -3- (tert-butyloxycarbonylamino) -piperidin-1-yl] xanthine (the product contains ca. 15% Z isomer)

Rf value: 0.35 (silica gel, cyclohexane / ethyl acetate = 3: 7)

Mass Spectrum (ESI⁺): m / z = 419 [M + H]⁺ (25) 3-Methyl-7 - ((E) -2-buten-1-yl) -8 - [(7?) -3- (tert-butyloxycarbonylamino) -piperidin-1-yl] xanthine (the product contains ca. 15% Z isomer)

Rf value: 0.35 (silica gel, cyclohexane / ethyl acetate = 3: 7)

Mass Spectrum (ESI⁺): m / z = 419 [M + H]⁺ (26) 1- [2- (2-hydroxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(7?) - 3- ( tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 551 [M + H]⁺ (27) 1- [2- (2-Amino-phenyl) -2-oxo-ethyl] -3-methyl-7 - [(1-cyclopenten-1-yl) methyl] -8- [3- (tert-butyloxycarbonylamino) ) -piperidin-1-yl] -xanthine Mass Spectrum (ESI⁺): m / z = 578 [M + H]⁺ (28) 1- (2-Phenyl-2-oxo-ethyl) -3-methyl-7 - [(1-cyclopenten-1-yl) methyl] -8- [3- (tert-butyloxycarbonylamino) -piperidine-1- yl] -xanthine Mass Spectrum (ESI⁺): m / z = 563 [M + H]⁺ (29) 1- [2- (2-hydroxy-phenyl) -2-oxo-ethyl] -3-methyl-7 - [(1-cyclopenten-1-yl) methyl] - 8- [310 (tert-butyloxycarbonyl) lamino) -piperidin-1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 579 [M + H]⁺ (30) 1-methyl-3-isopropyl-7- (2-cyano-benzyl) -8- [3- (tert-butyloxycarbonylamino) piperidin-1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 522 [M + H]⁺ (31) 1- [2- (2-hydroxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 - [3- (tert-butyloxycarbonylamino) - piperidin-1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 551 [M + H]⁺ (32) 1- [2- (2-Amino-phenyl) -2-oxo-ethyl] -3-methyl-7 - ((E) -2-buten-1-yl) -8- [3- (tert-butyloxycarbonyl) lamino) -piperidin-1-yl] -xanthine (the product contains about 10% Z-isomer)

Rf value: 0.20 (silica gel, cyclohexane / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z = 552 [M + H]⁺ (33) 1- (2-Phenyl-2-oxo-ethyl) -3-methyl-7 - ((E) -2-buten-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidine 1-yl] -xanthine (the product contains about 25% Z-isomer)

Mass Spectrum (ESI⁺): m / z = 537 [M + H]⁺ (34) 1- [2- (2-hydroxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(7?) - 3- ( tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine (35) 1- [2- (2-hydroxy-phenyl) -2-oxo-ethyl] -3-methyl-7 - ((E) -2-butene 1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine (the product contains some Z-isomer)

Rf value: 0.30 (silica gel, cyclohexane / ethyl acetate = 4: 6)

Mass Spectrum (ESI⁺): m / z = 553 [M + H]⁺ (36) 1- [2- (2-hydroxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(5) -3- (tert-butyloxycarbonyl) lamino) -piperidin-1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 551 [M + H]⁺ (37) 1- [2- (2-Amino-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) - piperidin-1-yl] -xanthine

Rf value: 0.50 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 550 [M + H]⁺ (38) 1- [2- (2-hydroxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8 - [(5) - 3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 567 [M + H]⁺ (39) 1- (2-Phenyl-2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8 - [(5) -3- (tert-butyloxycarbonylamino) -piperidine 1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 535 [M + H]⁺ (40) 1-methyl-3 - [(2-trimethylsilanyl-ethoxy) methyl] -7- (2-cyano-benzyl) -8- [3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine Mass spectrum ( ESI⁺): m / z = 610 [M + H]⁺ (41) 3-Methyl-7- (2-butyn-1-yl) -8 - [(5) - 3- (tert-butyloxycarbonylamino) -piperidin-1-yl] xanthine (Potassium carbonate)

Rf value: 0.52 (silica gel, ethyl acetate)

Mass Spectrum (ESI⁺): m / z = 417 [M + H]⁺ (42) 1- (2-Phenyl-2-oxo-ethyl) -3-methyl-7- (2-methyl-allyl) -8- [3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.46 (silica gel, methylene chloride / methanol = 95: 5) (43) 1- (2-phenyl-2-oxo-ethyl) -3-methyl-7- (3-bromo-allyl) -8 - [3- (tert-Butyloxycarbonylamino) piperidin-1-yl] -xanthine

Rf value: 0.22 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z - 601, 603 [M + H]⁺ (44) 1- (2-Phenyl-2-oxo-ethyl) -3-methyl-7 - [(furan-2-yl) methyl] -8- [3- (tert-butyloxycarbonylamino) -piperidin-1-yl ] -xantine

Rf value: 0.41 (silica gel, methylene chloride / methanol = 95: 5) (45) 1- (2-phenyl-2-oxo-ethyl) -3-methyl-7- (2-chloro-allyl) -8 - [3- (tert-Butyloxycarbonylamino) piperidin-1-yl] -xanthine

Rf value: 0.49 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 557, 559 [M + H]⁺ (46) 1- (2-Phenyl-2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8 - [(S) -3- (tert-butyloxycarbonylamino) -piperidine 1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 535 [M + H]⁺ (47) 1- [2- (2-Amino-phenyl) -2-oxo-ethyl] -3-methyl-7 - ((E) -2-buten-1-yl) -8 - [(5) - 3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.40 (silica gel, cyclohexane / ethyl acetate = 4: 6)

Mass Spectrum (ESI⁺): m / z = 552 [M + H]⁺ (48) 1- [2- (2-nitro-phenyl) -2-oxo-ethyl] -3-methyl-7 - ((E) -2-buten-1-yl) -8 - [(7?) -3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.50 (silica gel, cyclohexane / ethyl acetate = 1: 2) (49) 1- [2- (2-nitrophenyl) -2-oxo-ethyl] -3-methyl-7 - ((E ) -2-Buten-1-yl) -8 - [(5) -3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine Mass Spectrum (ESI)⁺): m / z = 582 [M + H]⁺ (50) 1- [2- (2-nitro-3-methoxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [ 3 (tert-Butyloxycarbonylamino) -piperidin-1-yl] -xanthine Mass Spectrum (ESI⁺): m / z = 626 [M + H]⁺ (51) 1- (2- {2-Oxo-3 - [(2-trimethylsilanyl-ethoxy) methyl] -2,3-dihydro-benzooksazol-7-yl} -210-oxo-ethyl) -3-methyl -7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butyloxycarbonylamino) piperidin-1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 738 [M + H]⁺ (52) 1- (2-Phenyl-2-oxo-ethyl) -3-methyl-7 - ((Z) -2-methyl-2-buten-1-yl) -8- [3- (tert-butyloxycarbonylamino) ) -piperidin-1-yl] -xanthine

Rf value: 0.48 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 551 [M + H]⁺ (53) 1- (2-Phenyl-2-oxo-ethyl) -3-methyl-7 - ((E) -2-methyl-2-buten-1-yl) -8- [3- (tert-butyloxycarbonylamino) ) -piperidin-1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 551 [M + H]⁺ (54) 1- (2- {2-Oxo-3 - [(2-trimethylsilanyl-ethoxy) methyl] -2,3-dihydro-benzoxazol-4-yl} -2oxo-ethyl) -3-methyl 7- (2-Butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidin-1-yl] xanthine

Rf value: 0.40 (silica gel, petroleum ether / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z = 722 [M + H]⁺ (55) 1- [2- (2,2-Difluoro-benzo [1,3] dioxol-4-yl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -830 [(R) -3 - (tert-butyl oxycarbonylamino) -piperidin-1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 615 [M + H]⁺ (56) 1- [2- (2,2-difluoro-benzo [1,3] dioxol-4-yl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 [(5) -3- (tert-butyloxycarbonylamino) -piperidin-l-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 615 [M + H]⁺ (5) 1 - [(1-methyl-1 H -indol-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) ) -piperidin-1-yl] -xanthine

Rf value: 0.80 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 560 [M + H]⁺ (58) 1 - [(quinolin-3-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidin-1-yl] - xanthine

Rf value: 0.50 (silica gel, ethyl acetate)

Mass Spectrum (ESI⁺): m / z = 558 [M + H]⁺ (59) 1- {[1- (tert-Butyloxycarbonylamino) -1H-indol-2-yl] methyl} -3-methyl-7- (2-butyn-1-yl) 8- [3- (tert -butyloksykarbonylamino) -piperidin-l-yl] -xanthine

Rf value: 0.40 (silica gel, petroleum ether / ethyl acetate - 1: 1)

Mass Spectrum (ESI⁺): m / z = 646 [M + H]⁺ (60) 1 - [(2-methyl-1 - [(2-trimethylsilanyl-ethoxy) methyl] -1H-benzoimidazol-5-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-Butyloxycarbonylamino) -piperidin-1-yl] -xanthine (mixed with 1 - [(2-methyl-3 - [(2-trimethylsilanyl-ethoxy) methyl] -3H-benzoimidazole) 5-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine) Rf value: 0.15 (silica gel , ethyl acetate)

Mass Spectrum (ESI⁺): m / z = 691 [M + H]⁺ (61) 1- [2- (Quinolin-8-yl -] - 2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.35 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 586 [M + H]⁺ (62) 1 - [(1 - [(2-trimethylsilanyl-ethoxy) methyl] -1,7-benzoimidazol-5-yl) methyl] -3-methyl-7- (2butyn-1-yl) -8- [ 3- (tert-Butyloxycarbonylamino) -piperidin-1-yl] -xanthine (mixed with 1 - [(3336641 [(2-trimethylsilanyl-ethoxy) methyl] -3 H -benzoimidazol-5-yl) methyl] -3- methyl-7- (2-butyn-l-yl) 8- [3- (tert-butyloxycarbonylamino) -piperidin-l-yl] -xanthine)

Rf value: 0.23 (silica gel, ethyl acetate)

Mass Spectrum (ESI⁺): m / z = 677 [M + H]⁺ (63) 1 - [(pyrazolo [1,5-a] pyridin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) - piperidin-1-yl] -xanthine

Rf value: 0.46 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z - 547 [M + H]⁺ (64) 1- (2-Phenyl-2-oxo-ethyl) -3-methyl-7 - ((E) -1-buten-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidine-1 -yl] -xanthine

Rf value: 0.48 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 537 [M + H]⁺ (65) 1- {2- [1- (tert-Butyloxycarbonyl) -17β-indol-7-yl] -2-oxo-ethyl} -3-methyl-7- (2-butynyl) -8- [3- (tert-butyloxycarbonylamino) -piperidin-l-yl] -xanthine

Rf value: 0.38 (silica gel, petroleum ether / ethyl acetate = 1: 1) (66) 1 - [(3-methyl-isoquinolin-1-yl) methyl] -3-methyl 1-7- (3-methyl) 1-butene-1-yl) - 8- [(7?) -3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.40 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 588 [M + H]⁺ (67) 1,3-Dimethyl-7- (2-bromo-benzyl) -8- [3- (tert-butyloxycarbonylamino) -piperidin-1-yl] xanthine

Rf value: 0.40 (silica gel, cyclohexane / ethyl acetate = 1: 1) (68) 1,3-dimethyl-7- (2-chlorobenzyl) -8- [3- (tert-butyloxycarbonylamino) -piperidine l-yl] xanthine

Rf value: 0.42 (silica gel, cyclohexane / ethyl acetate = 1: 1) (69) 1 - [(3-methyl-isoquinolin-1-yl) methyl] -3-methyl-7- (2-cyano-benzyl) ) -8- [3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 635 [M + H]⁺

Rf value: 0.40 (silica gel, cyclohexane / ethyl acetate = 3: 7) (70) 3-cyclopropyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidine 1-yl] xanthine

Mass Spectrum (ESI⁺): m / z = 443 [M + H]⁺

Rf value: 0.70 (silica gel, ethyl acetate) (71) 3-cyclopropyl-7- (2-butyn-1-yl) -8 - [(7?) - 3- (tert-butyloxycarbonylamino) -piperidine-1 yl] -xanthine

Rf value: 0.35 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 1)

Mass Spectrum (ESI⁺): m / z = 443 [M + H]⁺ (72) 1 - [(3-methyl-isoquinolin-1-yl) methyl] -3-methyl-7- (2-chloro-benzyl) -8 - [(7?) - 3- (tert-butyloxycarbonylamino) -piperidine -1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 644, 646 [M + H]⁺

Rf value: 0.39 (silica gel, cyclohexane / ethyl acetate = 1: 1) (73) 1 - [(3-methyl-isoquinolin-1-yl) methyl] -3-methyl-7- (2-bromo-benzyl) ) -8 - [(7?) - 3- (tert-Butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 644, 646 [M + H]⁺ (74) 1 - [(4-methyl-quinazolin-2-yl) methyl] -3-methyl-7- (2-chloro-benzyl) -8 - [(7?) - 3- (tert-butyloxycarbonylamino) -piperidine -1-yl] -xanthine

Prepared by reaction of (4-methyl-quinazolin-2-yl) methyl chloride and 3-methyl-7- (2-chlorobenzyl) -8-bromo-xanthine and then reacting with (7β) -3- (tert-butyloxycarbonylamino) -piperidine

Mass Spectrum (ESI⁺): m / z = 645, 647 [M + H]⁺ (75) 1 - [(4-phenyl-quinazolin-2-yl) methyl] -3-methyl-7- (2-chloro-benzyl) -8 - [(7?) - 3- (tert-butyloxycarbonylamino) -piperidine -1-yl] -xanthine

Prepared by reaction of (4-phenyl-quinazolin-2-yl) methyl chloride and 3-methyl-7- (2-chlorobenzyl) -8-bromo-xanthine and then reacting with (7β) -3- (tert-butyloxycarbonylamino) -piperidine

Mass Spectrum (ESI⁺): m / z = 707, 709 [M + H]⁺

Example IV 1- [2- (2-Hydroxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8-chloro-xanthine

Prepared by treating 1- [2- (2-methoxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2butene-1-yl) -8-chloro-xanthine with boron tribromide in methylene chloride. The desired product is contaminated by approx. 20% 1- [2- (2-hydroxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-bromo-3-methylbutyl) -8-chloro-xanthine.

Mass Spectrum (ESI⁺): m / z = 403, 405 [M + H]⁺

The following compounds are obtained analogously to Example IV:

(1) 1- [2- (2-hydroxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8-bromo-xanthine (the product is contaminated with ca. 20% 1- [2- (2-hydroxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (320 bromo-2-buten-1-yl) -8-bromo-xanthine)

Mass Spectrum (ESI⁺): m / z = 431, 433 [M + H]⁺ (2) 1- [2- (2-hydroxy-phenyl) -2-oxo-ethyl] -3-methyl-7 - [(1-cyclopenten-1-yl) methyl] -8-bromoxanthine

Mass Spectrum (ESI⁺): m / z = 459, 461 [M + H]⁺ (3) 1- [2- (2-hydroxy-phenyl) -2-oxo-ethyl] -3-methyl-7 - ((E) -2-buten-1-yl) -8-bromo-xanthine (the product contains some Z-isomer)

Rf value: 0.60 (silica gel, cyclohexane / ethyl acetate = 4: 6)

Mass Spectrum (ESI⁺): m / z = 433, 435 [M + H]⁺ (4) 1- [2- (2-hydroxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8-bromo-xanthine Mass Spectrum ( ESI⁺): m / z = 447, 449 [M + H]⁺

Example V 1- [2- (2-Methoxy-phenyl) -2-oxo-ethyl-3-methyl-7- (3-methyl-2-buten-1-yl) -8-chloro-xanthine

1.71 g of 2-bromo-1- (2-methoxy-phenyl) -ethanone are added to a mixture of 2.00 g of 3-methyl-7- (3-methyl-2-buten-1-yl) -8-chloro -xanthine and 1.38 mg of potassium carbonate in 15 ml of N, N-dimethylformamide. The reaction mixture is stirred for eight hours at ambient temperature. After aqueous workup, the crude product is purified by chromatography through a silica gel column with cyclohexane / ethyl acetate (8: 1 to 8: 1) as eluent.

Yield: 2.61 g (84% of theoretical value)

Mass Spectrum (ESI⁺): m / z - 417, 419 [M + H]⁺

The following compounds are obtained analogously to Example V:

(1) 1- [2- (3-Hydroxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butyloxycarbonyl) lamino) -piperidin-1-yl] -xanthine (The reaction is carried out with 2-bromo-1- [3- (tert-butyldimethylsilanyloxy) -phenyl] -ethanone) Rf value: 0.40 (silica gel, cyclohexane / ethyl acetate = 3: 7)

Mass Spectrum (ESI⁺): m / z = 567 [M + H]⁺ (2) 1- (1-Methyl-2-oxo-2-phenyl-ethyl) -3-methyl-7- (3-methyl-2-buten-1-yl) -8-chloro-xanthine Mass Spectrum (ESI)⁺): m / z = 401, 403 [M + H]⁺ (3) 1- (2-cyanoethyl) -3-methyl-7- (2-cyano-benzyl) -8-chloro-xanthine

Mass Spectrum (ESI⁺): m / z = 391, 393 [M + Na]⁺ (4) 1- (2-Phenoxy-ethyl) -3-methyl-7- (2-cyano-benzyl) -8- [3- (tert-butyloxycarbonylamino) piperidin-1-yl] -xanthine

Rf value: 0.90 (silica gel, methylene chloride / methanol = 9: 1)

Mass Spectrum (ESI⁺): m / z = 600 [M + H]⁺ (5) 1- (2-Phenyl-2-oxo-ethyl) -3 - [(2-trimethylsilanyl-ethoxy) methyl] -7- (3-methyl-2-buten-1-yl) -8 [3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 667 [M + H]⁺ (6) 1- (2-Methoxy-ethyl) -3-methyl-7- (2-cyano-benzyl) -8- [3- (tert-butyloxycarbonylamino) piperidin-1-yl] -xanthine

Rf value: 0.90 (silica gel, methylene chloride / methanol = 9: 1)

Mass Spectrum (ESI⁺): m / z = 538 [M + H]⁺ (7) 1-methyl-3 - [(2-trimethylsilanyl-ethoxy) methyl] -7- (2-cyano-benzyl) -xanthine

Rf value: 0.60 (silica gel, cyclohexane / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z - 412 [M + H]⁺ (8) 1- [2- (3-nitro-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8-chloro-xanthine R f value: 0.40 (silica gel, cyclohexane / ethyl acetate / methanol = 7: 2: 1)

Mass Spectrum (ESI⁺): m / z = 432, 434 [M + H]⁺ (9) 1- (2-Phenyl-2-oxo-ethyl) -3-methyl-7 - [(2-trimethylsilanyl-ethoxy) methyl] -8-bromo-xanthine Mass Spectrum (ESI)⁺): m / z = 493, 495 [M + H]⁺ (10) 1- [2- (2-nitro-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8-chloro-xanthine R value: 0.64 (silica g el, cyclohexane / ethyl acetate = 3: 7)

Mass Spectrum (ESI⁺): m / z = 432, 434 [M + H]⁺ (11) 1- [2- (2-nitro-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8-bromo-xanthine Mass spectrum ( ESI⁺): m / z = 476, 478 [M + H]⁺ (12) 1 - [(Quinolin-2-yl) methyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidine-1 -yl] -xanthine

Rf value: 0.45 (silica gel, ethyl acetate / petroleum ether = 7: 3)

Mass Spectrum (ESI⁺): m / z = 574 [M + H]⁺ (13) 1 - [(2-oxo-2/7-chromene-4-yl) methyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- ( tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine (The starting material 4-bromomethyl-chromen-2-one is prepared analogously to Kimura et al., Chem. Pharm. Bull. 1982, 30, 552-558.)

Rf value: 0.52 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 591 [M + H]⁺ (14) 1 - [(1-methyl-2-oxo-1,2-dihydro-quinolin-4-yl) methyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8 - [3- (tert-butyloxycarbonylamino) -piperidin-l-yl] -xanthine

Rf value: 0.54 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 604 [M + H]⁺ (15) 1- [(quinazolin-4-yl) methyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidine-1 -yl] -xanthine

Melting point: 195-197 ° C

Mass Spectrum (ESI⁺): m / z = 575 [M + H]⁺ (16) 1 - [(5-methyl-3-phenyl-isoxazol-4-yl) methyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3 (tert) -butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.40 (silica gel, cyclohexane / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z - 604 [M + H]⁺ (17) 1 - [(3-phenyl- [1,2,4] oxadiazol-5-yl) methyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [ 3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.18 (silica gel, petroleum ether / ethyl acetate = 2: 1)

Mass Spectrum (ESI⁺): m / z = 591 [M + H]⁺ (18) 1 - [(4-phenyl-pyridin-2-yl) methyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butyloxycarbonylamino) - piperidin-1-yl] -xanthine

Rf value: 0.53 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 600 [M + H]⁺ (19) 1 - [(5-phenyl-pyridin-2-yl) methyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butyloxycarbonylamino) - piperidin-1-yl] -xanthine

Rf value: 0.73 (silica gel, ethyl acetate)

Mass Spectrum (ESI⁺): m / z = 600 [M + H]⁺ (20) 1- [2- (3-methylsulfanyl-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butyloxycarbonyl) lamino) -piperidin-1-yl] -xanthine

Rf value: 0.43 (silica gel, cyclohexane / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z = 597 [M + H]⁺ (21) 1- [2- (3-Methoxycarbonyl-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3 (tert) -butyloxycarbonylamino) -piperidin-1-yl] -xanthine (Made in N-methylpyrrolidin-2-one at 60 ° C)

Rf value: 0.27 (silica gel, methylene chloride / methanol = 20: 1)

Mass Spectrum (ESI⁺): m / z - 609 [M + H]⁺ (22) 1- [2- (2-Ethoxycarbonyl-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3 (tert. butyloxycarbonylamino) -piperidin-1-yl] -xanthine (Made in N-methylpyrrolidin-2-one at 60 ° C)

Rf value: 0.35 (silica gel, methylene chloride / methanol = 20: 1)

Mass Spectrum (ESI⁺): m / z = 623 [M + H]⁺ (23) 1- [2- (2,6-Dimethoxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine (Done in N-methylpyrrolidin-2-one at 60 ° C)

Rf value: 0.53 (silica gel, methylene chloride / methanol = 20: 1)

Mass Spectrum (ESI⁺): m / z = 611 [M + H]⁺ (24) 1- (2-Phenyl-2-oxo-ethyl) -3-methyl-7- (2,3-dimethyl-2-buten-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidine -1-yl] -xanthin (Made in N-methylpyrrolidin-2-one at 60 ° C)

Rf value: 0.38 (silica gel, methylene chloride / methanol = 20: 1)

Mass Spectrum (ESI⁺): m / z = 565 [M + H]⁺ (25) 1- ((E) -3-phenyl-allyl) -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidine 1-yl] -xanthine

Rf value: 0.54 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 95: 5: 0.1) Mass Spectrum (ESI⁺): m / z = 549 [M + H]⁺ (26) 1 - [(1-Benzo [Z&gt;] thiophen-3-yl) methyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butyloxycarbonyl) lamino) -piperidin-1-yl] -xanthine

Rf value: 0.75 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 579 [M + H]⁺ (27) 1- {[1- (tert-Butyloxycarbonyl) -indol-3-yl] methyl} -3-methyl-7- (3-methyl-2-buten-1-yl) -8 [3- (tert (butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.61 (silica gel, methylene chloride / methanol - 9: 1)

Mass Spectrum (ESI⁺): m / z - 662 [M + H]⁺ (28) 1- [(biphenyl-4-yl) methyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidine-1- yl] -xanthine

Rf value: 0.68 (silica gel, cyclohexane / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z = 599 [M + H]⁺ (29) 1 - [(1-Naphthyl) methyl] -3-methyl-7- (2-butyn-1-yl) 8- [3- (tert-butyloxycarbonylamino) piperidin-1-yl] -xanthine

Rf value: 0.83 (silica gel, ethyl acetate / petroleum ether = 4: 1)

Mass Spectrum (ESI⁺): m / z = 557 [M + H]⁺ (30) 1 - [(1-methyl-2-oxo-1,2-dihydro-quinolin-4-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3 (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.25 (silica gel, ethyl acetate / petroleum ether = 4: 1)

Mass Spectrum (ESI⁺): m / z = 588 [M + H]⁺ (31) 1- (2-Cyclohexyl-2-oxo-ethyl) -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidine-1 -yl] -xanthine

Melting point: 163-165 ° C

Mass Spectrum (ESI⁺): m / z = 557 [M + H]⁺ (32) 1- (3,3-Dimethyl-2-oxo-butyl) -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidine -1-yl] -xanthine

Rf value: 0.95 (silica gel, ethyl acetate / petroleum ether = 4: 1)

Mass Spectrum (ESI⁺): m / z = 531 [M + H]⁺ (33) 1 - [(quinazolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidin-1-yl] - xanthine

Rf value: 0.40 (silica gel, ethyl acetate)

Mass Spectrum (ESI⁺): m / z = 559 [M + H]⁺ (34) 1- [(2-methyl-naphthalen-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidine-1- yl] -xanthine

Rf value: 0.80 (silica gel, ethyl acetate)

Mass Spectrum (ESI⁺): m / z = 571 [M + H]⁺ (35) 1 - [(5-nitro-isoquinolin-1-yl) methyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butyloxycarbonylamino) - piperidin-1-yl] -xanthine

Rf value: 0.54 (silica gel, methylene chloride / methanol = 95: 5) (36) 1- (2-dimethylamino-2-oxo-ethyl) -3-methyl-7- (3-methyl-2-butene) 1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.23 (silica gel, ethyl acetate)

Mass Spectrum (ESI⁺): m / z = 518 [M + H]⁺ (37) 1- [2- (piperidin-1-yl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butyloxycarbonyl) lamino) -piperidin-1-yl] -xanthine

Rf value: 0.44 (silica gel, ethyl acetate)

Mass Spectrum (ESI⁺): m / z = 558 [M + H]⁺ (38) 1 - [(2-methyl-1-oxo-1,2-dihydro-isoquinolin-4-yl) methyl] -7- (2-butyn-1-yl) - 8- [3- (tert-butyloxycarbonylamino) ) -piperidin-1-yl] -xanthine

Rf value: 0.25 (silica gel, ethyl acetate)

Mass Spectrum (ESI⁺): m / z = 588 [M + H]⁺ (39) 1 - [(2-methyl-1-oxo-1,2-dihydro-isoquinolin-4-yl) methyl] -7- (3-methyl-2-buten-1-yl) -8- [3 (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.30 (silica gel, ethyl acetate)

Mass Spectrum (ESI⁺): m / z = 604 [M + H]⁺ (40) 1 - [(2-methoxy-naphthalen-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidine-1 - yl] -xanthine

Rf value: 0.75 (silica gel, ethyl acetate)

Mass Spectrum (ESI⁺): m / z - 587 [M + H]⁺ (41) 1 - [(4-methoxy-naphthalen-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) - 8- [3- (tert-butyloxycarbonylamino) -piperidine-1 - yl] -xanthine

Rf value: 0.80 (silica gel, ethyl acetate)

Mass Spectrum (ESI⁺): m / z = 587 [M + H]⁺ (42) 1 - [(3-methyl-isoquinolin-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidine-1 - yl] -xanthine

Rf value: 0.56 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 572 [M + H]⁺ (43) 1- [2- (2,3-Dimethoxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.83 (silica gel, ethyl acetate)

Mass Spectrum (ESI⁺): m / z = 611 [M + H]⁺ (44) 1 - [(5-nitro-naphthalen-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidine-1 -yl] -xanthine

Rf value: 0.78 (silica gel, ethyl acetate)

Mass Spectrum (ESI⁺): m / z = 602 [M + H]⁺ (45) 1- [2- (Pyrrolidin-1-yl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butyloxycarbonyl) lamino) -piperidin-1-yl] -xanthine

Rf value: 0.39 (silica gel, ethyl acetate)

Mass Spectrum (ESI⁺): m / z = 544 [M + H]⁺ (46) 1 - [(4-methyl-isoquinolin-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidin-1-yl ] xanthine

Rf value: 0.56 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 572 [M + H]⁺ (47) 1 - [(2-naphthyl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) piperidin-1-yl] -xanthine

Rf value: 0.78 (silica gel, ethyl acetate)

Mass Spectrum (ESI⁺): m / z = 557 [M + H]⁺ (48) 1-cyanomethyl-3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) piperidin-1-yl] -xanthine

Rf value: 0.80 (silica gel, ethyl acetate)

Mass Spectrum (ESI⁺): m / z = 456 [M + H]⁺ (49) 1 - [(Quinolin-6-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) piperidin-1-yl] -xanthine

Rf value: 0.40 (silica gel, ethyl acetate)

Mass Spectrum (ESI⁺): m / z = 558 [M + H]⁺ (50) 1 - [(3-methoxy-naphthalen-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) - 8- [3- (tert-butyloxycarbonylamino) -piperidine-1- yl] -xanthine

Rf value: 0.83 (silica gel, ethyl acetate)

Mass Spectrum (ESI⁺): m / z = 587 [M + H]⁺ (51) 1- [2- (2,3-dihydro-benzo [1,4] dioxin-5-yl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-butene) 1 yl) -8- [3- (tert-Butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.38 (silica gel, ethyl acetate / petroleum ether = 1: 1)

Mass Spectrum (ESI⁺): m / z = 609 [M + H]⁺ (52) 1- [2- (3-Methyl-2-oxo-2,3-dihydro-benzooksazol-7-yl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2'-butene) 1-yl) -8- [3- (tert-Butyloxycarbonylamino) -piperidin-1-yl] -xanthine (Done with potassium tert-butoxide in dimethylsulfoxide)

Rf value: 0.48 (silica gel, ethyl acetate / petroleum ether = 2: 1)

Mass Spectrum (ESI⁺): m / z = 622 [M + H]⁺ (53) 1- [2- (benzo [1,3] dioxol-4-yl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) - 8 - [3 (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z - 595 [M + H]⁺ (54) 1 - [(quinazolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert-butyloxycarbonylamino) -piperidine-1 - yl] -xanthine Mass Spectrum (ESI⁺): m / z = 559 [M + H]⁺ (55) 1 - [(quinazolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(S) -3- (tert-butyloxycarbonylamino) -piperidine-1 - yl] -xanthine Mass Spectrum (ESI⁺): m / z - 559 [M + H]⁺ (56) 1 - [(quinazolin-2-yl) methyl] -3-methyl-7 - ((E) -2-buten-1-yl) -8 - [(S) -3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine (the product contains about 15% Z-isomer)

Rf value: 0.30 (silica gel, ethyl acetate / cyclohexane = 8: 2)

Mass Spectrum (ESI⁺): m / z = 561 [M + H]⁺ (57) 1 - [(quinazolin-2-yl) methyl] -3-methyl-7 - ((E) -2-buten-1-yl) -8 - [(7?) - 3- (tert-butyloxycarbonylamino) ) -piperidin-1-yl] -xanthine (the product contains about 15% Z-isomer)

Rf value: 0.30 (silica gel, ethyl acetate / cyclohexane = 8: 2)

Mass Spectrum (ESI⁺): m / z = 561 [M + H]⁺ (5) 1 - [(3-methyl-isoquinolin-1-yl) methyl] -3-methyl-7 - ((E) -2-buten-1-yl) -8- [(/ 2) - 3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine (the product contains about 17% Z-isomer)

Rf value: 0.58 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 574 [M + H]⁺ (59) 1 - [(3-methyl-isoquinolin-1-yl) methyl] -3-methyl-7 - ((E) -2-buten-1-yl) -8- [(5) -3 - (tert-butyloxycarbony lamino) -piperidin-1-yl] -xanthine (the product contains about 17% Z-isomer)

Rf value: 0.58 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 574 [M + H]⁺ (60) 1- [2- (2-Methoxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8-bromo-xanthine Mass Spectrum (ESI)⁺): m / z = 445, 447 [M + H]⁺ (61) 1- [2- (2-nitro-phenyl) -2-oxo-ethyl] -3-methyl-7 - [(1-cyclopenten-1-yl) methyl] -8-bromoxanthine

Mass Spectrum (ESI⁺): m / z = 488, 490 [M + H]⁺ (62) 1- [2- (2-methoxy-phenyl) -2-oxo-ethyl] -3-methyl-7 - [(1-cyclopenten-1-yl) methyl] -8-bromoxanthine

Mass Spectrum (ESI⁺): m / z = 473, 475 [M + H]⁺ (63) 1 - [(isoquinolin-1-yl) methyl] -3 - [(methoxycarbonyl) methyl] -7- (3-methyl-2-buten-1-yl) - 8 [3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine Rf value: 0.35 (silica gel, methylene chloride / methanol = 95: 5) (64) 1- [2- (2-nitro-phenyl) -2-oxo-ethyl] - 3-methyl-7 - ((E) -2-buten-1-yl) -8-bromo-xanthine (the product contains about 10% Z-isomer)

Rf value: 0.60 (silica gel, cyclohexane / ethyl acetate = 4: 6)

Mass Spectrum (ESI⁺): m / z = 462, 464 [M + H]⁺ (65) 1- [2- (2-Methoxy-phenyl) -2-oxo-ethyl] -3-methyl-7 - ((E) -2-buten-1-yl) -8-bromo-xanthine (the product contains some Z-isomer)

Rf value: 0.30 (silica gel, cyclohexane / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z = 447, 449 [M + H]⁺ (66) 1- [2- (2-nitro-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8-bromo-xanthine Rf value: 0, 77 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 460, 462 [M + H]⁺ (67) 1- (2-Phenyl-2-oxo-ethyl) -3-methyl-7 - ((E) -2-buten-1-yl) -8 - [(R) -3- (tert-butyloxycarbonylamino) ) -piperidin-1-yl] -xanthine (the product contains about 20% Z-isomer)

Mass Spectrum (ESI⁺): m / z - 537 [M + H]⁺ (68) 1- [2- (2-Methoxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8-bromo-xanthine Mass Spectrum ( ESI⁺): m / z = 461, 463 [M + H]⁺ (69) 1- (2-Phenyl-2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8-bromo-xanthine Rf value: 0.61 (silica gel, cyclohexane / ethyl acetate = 4: 6) (70) 1- (2- {2 - [(ethylaminocarbonyl) methoxy] phenyl} -2-oxo-ethyl) -3-methyl-7 - ((E) -2-butene l yl) -8 - [(R) - 3- (tert-Butyloxycarbonylamino) -piperidin-1-yl] -xanthine (the product contains about 17% Z-isomer)

Mass Spectrum (ESI⁺): m / z = 638 [M + H]⁺ (71) 1- (2-Phenyl-2-oxo-ethyl) -3-methyl-7 - ((E) -2-buten-1-yl) -8 - [(5) -3- (tert-butyloxycarbonylamino) ) -piperidin-1-yl] -xanthine (the product contains about 18% Z-isomer)

Rf value: 0.35 (silica gel, cyclohexane / ethyl acetate = 6: 4)

Mass Spectrum (ESI⁺): m / z = 537 [M + H]⁺ (72) 1- [2- (2-nitro-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(5) -3- (tert-butyloxycarbonyl) lamino) -piperidin-1-yl] -xanthine

Rf value: 0.60 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 580 [M + H]⁺ (73) 1 - [(3-methyl-isoquinolin-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(5) -3- (tert-butyloxycarbonylamino) - piperidin-1-yl] -xanthine

Rf value: 0.52 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 572 [M + H]⁺ (74) 1 - [(3-methyl-isoquinolin-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) - 3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 572 [M + H]⁺ (75) 1 - [(4-methyl-isoquinolin-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(* S) -3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 572 [M + H]⁺ (76) 1 - [(4-methyl-isoquinolin-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(7?) -3 - (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 572 [M + H]⁺ (77) 1 - [(4-methyl-isoquinolin-1-yl) methyl] -3-methyl-7 - ((E) -2-buten-1-yl) -8 - [(* S) -3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.52 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 574 [M + H]⁺ (78) 1 - [(4-methyl-isoquinolin-1-yl) methyl] -3-methyl-7 - ((E) -2-buten-1-yl) -8- [(7?) - 3 - (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.52 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 574 [M + H]⁺ (79) 1- [2- (2,3-dihydro-benzo [1,4] dioxin-5-yl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 [(7?) - 3- (tert -butyl oxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.18 (silica gel, ethyl acetate / petroleum ether = 1: 1)

Mass Spectrum (ESI⁺): m / z = 593 [M + H]⁺ (80) 1- [2- (2,3-dihydro-benzo [1,4] dioxin-5-yl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 [(5) -3- (tert-butyloxycarbonylamino) -piperidin-l-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 593 [M + H]⁺ (81) 1 - [(4-methoxy-naphthalen-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) - 8- [(5) -3 - (tert-butyloxycarbonylamino) - piperidin-1-yl] -xanthine

Rf value: 0.56 (silica gel, petroleum ether / ethyl acetate = 1: 2)

Mass Spectrum (ESI⁺): m / z = 587 [M + H]⁺ (82) 1 - [(4-methoxy-naphthalen-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(5) -3 - (tert-butyloxycarbonylamino) - piperidin-1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 587 [M + H]⁺ (83) 1- [2- (benzo [1,3] dioxol-4-yl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(5) ) -3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.86 (silica gel, ethyl acetate / petroleum ether = 4: 1)

Mass Spectrum (ESI⁺): m / z - 579 [M + H]⁺ (84) 1- [2- (benzo [1,3] dioxol-4-yl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(5) ) -3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.86 (silica gel, ethyl acetate / petroleum ether = 4: 1)

Mass Spectrum (ESI⁺): m / z = 579 [M + H]⁺ (85) 1- [(4-methyl-quinazolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) - 8 - [(5) -3 - (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.48 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 573 [M + H]⁺ (86) 1 - [(4-methyl-quinazolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [(5) -3- (tert-butyloxycarbonylamino) - piperidin-1-yl] -xanthine

Rf value: 0.48 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 573 [M + H]⁺ (87) 1- [2- (3-Methyl-2-oxo-2,3-dihydro-benzooksazol-4-yl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-butene -1-yl) -8- [3- (tert-Butyloxycarbonylamino) -piperidin-1-yl] -xanthine Rf value: 0.50 (silica gel, petroleum ether / ethyl acetate = 1: 2)

Mass Spectrum (ESI⁺): m / z = 622 [M + H]⁺ (88) 1- (2- {2 - [(Ethylaminocarbonyl) methoxy] -phenyl} -2-oxo-ethyl) -3-methyl-7 - ((E) -2-buten-1-yl) -8- [ (S) -3- (tert-butyloxycarbonylamino) -piperidin-l-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 638 [M + H]⁺ (89) 1- (2- {2 - [(methylaminocarbonyl) methoxy] phenyl} -2-oxo-ethyl) -3-methyl-7 - ((E) -2-butenl-yl) -8 - [( 7?) - 3- (tert-Butyloxycarbonylamino) -piperidin-1-yl] -xanthine Mass Spectrum (ESI⁺): m / z = 624 [M + H]⁺ (90) 1- (2- {2 - [(methylaminocarbonyl) methoxy] -phenyl} -2-oxo-ethyl) -3-methyl-7 - ((E) -2-buten-1-yl) -8- [ (S) -3- (tert-Butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 624 [M + H]⁺ (91) 1- [2- (2-nitro-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert-butyloxycarbonyl) lamino) -piperidin-1-yl] -xanthine

Rf value: 0.60 (silica gel, methylene chloride / methanol = 95: 5) (92) 1- [2- (2-nitro-3-methoxy-phenyl) -2-oxo-ethyl] -3-methyl-7 - (3-methyl-2-butene-l-yl) -8brom xanthine

Mass Spectrum (ESI⁺): m / z = 506, 508 [M + H]⁺ (93) 1 - [(4-Dimethylamino-quinazolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidine-1- yl] -xanthine (Performed in the presence of cesium carbonate)

Rf value: 0.40 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 602 [M + H]⁺ (94) 1- (2- {2-Oxo-3 - [(2-trimethylsilanyl-ethoxy) methyl] -2,3-dihydro-benzooksazol-7-yl} -2oxo-ethyl) -3-methyl 7- (3-methyl-2-butene-1-yl) -8-bromo-xanthine

Rf value: 0.75 (silica gel, ethyl acetate / petroleum ether = 1: 1)

Mass Spectrum (ESI⁺): m / z = 618, 620 [M + H]⁺ (95) 1 - [(imidazo [1,2-a] pyridin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) - piperidin-1-yl] -xanthine

Rf value: 0.44 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 547 [M + H]⁺ (96) 1 - [(quinoxalin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidin-1-yl] - xanthine

Rf value: 0.50 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 559 [M + H]⁺ (97) 1- [2- (1,3-Dimethyl-2-oxo-2,3-dihydro-1H-benzoimidazol-4-yl) -2-oxo-ethyl] -3-methyl7- (2-butyne) 1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.50 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 619 [M + H]⁺ (98) 1 - [(quinoxalin-6-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.35 (silica gel, ethyl acetate)

Mass Spectrum (ESI⁺): m / z = 559 [M + H]⁺ (99) 1- (2- {2-oxo-3 - [(2-trimethylsilanyl-ethoxy) methyl] -2,3-dihydro-benzooksazol-4-yl} -2oxo-ethyl) -3-methyl 7- (2-butyn-l-yl) -8-bromo-xanthine

Rf value: 0.30 (silica gel, petroleum ether / ethyl acetate = 2: 1)

Mass Spectrum (ESI '): m / z = 600, 602 [MH]' (100) 1 - [(3-methyl-quinoxalin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) yl) -8- [3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.44 (silica gel, petroleum ether / ethyl acetate = 1: 2)

Mass Spectrum (ESI⁺): m / z = 573 [M + H]⁺ (101) 1 - [(3-Phenyl-isoquinolin-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidine-1 - yl] -xanthine

Rf value: 0.85 (silica gel, ethyl acetate)

Mass Spectrum (ESI⁺): m / z = 634 [M + H]⁺ (102) 1 - [(3,4-Dimethyl-isoquinolin-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidine 1-yl] -xanthine

Rf value: 0.60 (silica gel, ethyl acetate / methanol = 3: 1)

Mass Spectrum (ESI⁺): m / z - 586 [M + H]⁺ (103) 1 - [(benzofuran-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) - [(5) -3- (tert-butyloxycarbonylamino) -piperidin-1-yl ] -xantine

Mass Spectrum (ESI⁺): m / z = 547 [M + H]⁺ (104) 1- {[4- (morpholin-4-yl) -quinazolin-2-yl] methyl} -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) ) -piperidin-1-yl] -xanthine (Performed in the presence of cesium carbonate)

Rf value: 0.28 (silica gel, ethyl acetate)

Mass Spectrum (ESI⁺): m / z = 644 [M + H]⁺ (105) 1 - {[4- (piperidin-1-yl) -quinazolin-2-yl] methyl} -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) ) -piperidin-1-yl] -xanthine (Performed in the presence of cesium carbonate)

Rf value: 0.35 (silica gel, ethyl acetate)

Mass Spectrum (ESI⁺): m / z = 642 [M + H]⁺ (106) 1- ({4- [4- (tert-Butyloxycarbonyl) -piperazin-1-yl] -quinazolin-2-yl} methyl) -3-methyl-7 (2-butyn-1-yl) -8 - [3- (tert-Butyloxycarbonylamino) -piperidin-1-yl] -xanthine (Performed in the presence of cesium carbonate)

Rf value: 0.50 (silica gel, ethyl acetate)

Mass Spectrum (ESI⁺): m / z = 743 [M + H]⁺ (107) 1 - {[4- (Pyrrolidin-1-yl) quinazolin-2-yl] methyl} -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) ) -piperidin-1-yl] -xanthine (Performed in the presence of cesium carbonate)

Rf value: 0.59 (silica gel, ethyl acetate / methanol / conc. Aqueous ammonia = 95: 5: 0.1) Mass Spectrum (ESI⁺): m / z = 628 [M + H]⁺ (108) 1- [2- (1-Ethoxycarbonyl-3-methyl-2-oxo-2,3-dihydro-1H-benzoimidazol-4-yl) -2oxo-ethyl] -3-methyl-7- ( 2-butyn-l-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidin-l-yl] xanthine

Rf value: 0.25 (silica gel, petroleum ether / ethyl acetate = 1: 2)

Mass Spectrum (ESI⁺): m / z = 677 [M + H]⁺ (109) 1 - [(4-cyano-naphthalen-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(7?) - 3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.77 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 582 [M + H]⁺ (110) 1 - [(imidazo [1,2-a] pyridin-3-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) - piperidin-1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 547 [M + H]⁺ (111) 1- [(8-methyl-imidazo [1,2-a] pyridin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- ( tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.25 (silica gel, ethyl acetate)

Mass Spectrum (ESI⁺): m / z = 561 [M + H]⁺ (112) 1 - [(8-methoxy-quinolin-5-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidine-1 - yl] -xanthine

Rf value: 0.60 (silica gel, ethyl acetate / methanol = 9: 1)

Mass Spectrum (ESI⁺): m / z = 588 [M + H]⁺ (113) 1 - [(5-methoxy-quinolin-8-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidine-1 - yl] -xanthine

Rf value: 0.40 (silica gel, methylene chloride / methanol = 20: 1)

Mass Spectrum (ESI⁺): m / z = 588 [M + H]⁺ (114) 1 - [(4-Phenyl-quinazolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidine-1- yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 635 [M + H]⁺ (115) 1- [(7-methyl-imidazo [1,2-a] pyridin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- ( tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.50 (silica gel, methylene chloride / methanol - 95: 5)

Mass Spectrum (ESI⁺): m / z = 561 [M + H]⁺ (116) 1- (2-Oxo-4-phenyl-butyl) -3-methyl-7- (2-butyn-1-yl) -8 - [(7?) - 3- (tert-butyloxycarbonylamino) -piperidine 1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 563 [M + H]⁺ (117) 1- (2- {2-oxo-1,3-bis - [(2-trimethylsilanyl-ethoxy) methyl] -2,3-dihydro-1,7-benzoimidazol-4-yl} -2-oxo-ethyl ) -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.50 (silica gel, ethyl acetate / petroleum ether = 1: 1)

Mass Spectrum (ESI⁺): m / z = 851 [M + H]⁺ (118) 1 - [(3-difluoromethyl-isoquinolin-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidine-1- yl] -xanthine (By-product of the reaction of 3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine with 1-chloromethyl-3 -trifhiormetyl-3,4-dihydroisoquinoline)

Rf value: 0.75 (alumina, petroleum ether / ethyl acetate = 1: 2)

Mass Spectrum (ESI⁺): m / z = 608 [M + H]⁺ (119) 1- [2- (2,2-Difluoro-benzo [1,3] dioxol-4-yl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8brom-xanthine

Mass Spectrum (ESI⁺): m / z = 495, 497 [M + H]⁺ (120) 1- [(3-methyl-imidazo [1,2-a] pyridin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- ( tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.50 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 561 [M + H]⁺ (121) 1- [(5-methyl-imidazo [1,2-a] pyridin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- ( tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.50 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z - 561 [M + H]⁺ (122) 1- [(6-methyl-imidazo [1,2-a] pyridin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- ( tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.10 (silica gel, ethyl acetate / methanol = 98: 2)

Mass Spectrum (ESI⁺): m / z = 561 [M + H]⁺ (123) 1- [(3-Benzyl-imidazo [1,2-a] pyridin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- ( tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.60 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 637 [M + H]⁺ (124) 1 - [(4-isopropyl-quinazolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidine-1 - yl] -xanthine

Rf value: 0.50 (silica gel, ethyl acetate / petroleum ether = 8: 2)

Mass Spectrum (ESI⁺): m / z = 601 [M + H]⁺ (125) 1- [(2,3-dihydro-benzo [1,4] dioxin-6-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- ( tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.53 (silica gel, ethyl acetate / petroleum ether = 3: 2) (126) 1 - [(3-phenyl-imidazo [1,2-a] pyridin-2-yl) methyl] -3-methyl 7- (2-Butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.50 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 623 [M + H]⁺ (127) 1- [2- (Naphthalen-1-yl] -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidine -1-yl] -xanthine

Rf value: 0.54 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 585 [M + H]⁺ (128) 1 - [(5-methoxy-isoquinolin-8-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidine-1 - yl] -xanthine

Rf value: 0.50 (silica gel, ethyl acetate / methanol = 24: 1)

Mass Spectrum (ESI⁺): m / z = 588 [M + H]⁺ (129) 1 - [(3-difluoromethyl-isoquinolin-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidine-1- Yl] -xanthine (By-product of the reaction of 3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine with 1-chloromethyl-3 trifluoromethyl-3,4-dihydroisoquinoline)

Rf value: 0.75 (alumina, petroleum ether / ethyl acetate = 1: 2)

Mass Spectrum (ESI⁺): m / z = 608 [M + H]⁺ (130) 1- {[1- (1-Cyano-1-methyl-ethyl) -isoquinolin-3-yl] methyl} -3-methyl-7- (2-butyn-1-yl) -8- [3 (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.75 (silica gel, ethyl acetate)

Mass Spectrum (ESI⁺): m / z = 625 [M + H]⁺ (132) 1-Methoxycarbonylmethyl-3-methyl-7- (2-butyn-1-yl) - 8- [3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 489 [M + H]⁺ (133) 1 - [(4-phenyl-quinazolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(7?) - 3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 635 [M + H]⁺ (134) 1 - [(2,3-Dimethyl-quinoxalin-6-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidine 1-yl] -xanthine (Performed in the presence of cesium carbonate)

Rf value: 0.40 (silica gel, ethyl acetate)

Mass Spectrum (ESI⁺): m / z = 587 [M + H]⁺ (135) 1 - [(4-phenyl-quinazolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(S) -3- (tert-butyloxycarbonylamino) - piperidin-1-yl] -xanthine

Rf value: 0.55 (silica gel, ethyl acetate / petroleum ether - 8: 2)

Mass Spectrum (ESI⁺): m / z - 635 [M + H]⁺ (136) 1- [2- (Quinolin-8-yl -] - 2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8-bromo-xanthine Rf value: 0 55 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 466, 468 [M + H]⁺ (137) 1 - [(3,4-Dimethyl-6,7-dihydro-5H- [2] pyrindin-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 [3- (tert-Butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.65 (alumina, ethyl acetate / petroleum ether = 3: 1)

Mass Spectrum (ESI⁺): m / z = 576 [M + H]⁺ (138) 1 - [(3,4-Dimethyl-5,6,7,8-tetrahydro-isoquinolin-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) 8- [ 3- (tert-butyloxycarbonylamino) -piperidin-l-yl] -xanthine

Rf value: 0.40 (alumina, methylene chloride / methanol = 20: 1)

Mass Spectrum (ESI⁺): m / z = 590 [M + H]⁺ (139) 1- {2- [1- (tert-Butyloxycarbonyl) -177-indol-4-yl] -2-oxo-ethyl} -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidin-l-yl] -xanthine

Rf value: 0.55 (silica gel, petroleum ether / ethyl acetate = 1: 2)

Mass Spectrum (ESI⁺): m / z = 674 [M + H]⁺ (140) 1 - [(1-methyl-2-oxo-1,2-dihydro-quinolin-6-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3 (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Mass spectrum (EI): m / z = 587 [M]⁺ (141) 1- ({1 - [(2-trimethylsilanyl-ethoxy) methyl] -2-oxo-1,2-dihydro-quinolin-6-yl} methyl) -3-methyl-7- (2-butyn-1- yl) -8- [3- (tert-Butyloxycarbonylamino) -piperidin-1-yl] -xanthine Mass Spectrum (ESI⁺): m / z = 704 [M + H]⁺ (142) 1 - [(2,3,8-trimethyl-quinoxalin-6-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) - piperidin-1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 601 [M + H]⁺ (143) 1 - [(8-methyl-quinoxalin-6-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidine-1 - yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 573 [M + H]⁺ (144) 1 - [(4-methyl-phthalazin-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidine-1- yl] -xanthine

Rf value: 0.65 (silica gel, methylene chloride / methanol = 9: 1)

Mass Spectrum (ESI⁺): m / z - 573 [M + H]⁺ (145) 1 - [(4-bromo-3-methoxy-isoquinolin-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) - piperidin-1-yl] -xanthine

Rf value: 0.65 (silica gel, methylene chloride / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z = 666, 668 [M + H]⁺ (146) 1 - [(4-difluoromethoxy-naphthalen-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert-butyloxycarbonylamino) - piperidin-1-yl] -xanthine

Rf value: 0.80 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 623 [M + H]⁺ (147) 1- {2- [1- (tert-Butyloxycarbonyl) -177-indol-7-yl] -2-oxo-ethyl} -3-methyl-7- (2-butyn-1-yl) -8- bromo-xanthine

Rf value: 0.83 (silica gel, methylene chloride / methanol = 95: 5) (148) 1 - [(E) -3- (2-nitrophenyl) -2-propen-1-yl] -3-methyl -7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 578 [M + H]⁺ (149) 1- ((E) -3-pentafluorophenyl-2-propen-1-yl) -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidine -1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 623 [M + H]⁺ (150) 1 - [(4-nitro-naphthalen-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(7?) - 3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.41 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 602 [M + H]⁺ (151) 1 - [(benzoxazol-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidin-1-yl] - xanthine

Rf value: 0.40 (silica gel, cyclohexane / ethyl acetate = 3: 7)

Mass Spectrum (ESI⁺): m / z - 548 [M + H]⁺ (152) 1 - [(5-nitro-benzoxazol-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidine-1-yl] yl] -xanthine

Rf value: 0.50 (silica gel, cyclohexane / ethyl acetate / methanol = 5: 4: 1)

Mass Spectrum (ESI⁺): m / z = 593 [M + H]⁺ (153) 1 - [(3-methyl-isoquinolin-1-yl) methyl] -3-methyl-7- (3-methyl-1-butene-1-yl) -8-bromo-xanthine Rf value: 0 65 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 468, 470 [M + H]⁺ (154) 1 - [(quinolin-7-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidin-1-yl] - xanthine

Mass Spectrum (ESI⁺): m / z = 558 [M + H]⁺ (155) 1 - [([1,5] naphthyridin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidine-1 -yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 559 [M + H]⁺ (156) 1 - [(8-methyl-quinoxalin-6-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert-butyloxycarbonylamino) - piperidin-1-yl] -xanthine

Rf value: 0.45 (silica gel, methylene chloride / methanol = 19: 1)

Mass Spectrum (ESI⁺): m / z = 573 [M + H]⁺ (157) 1 - [(2,3,8-trimethyl-quinoxalin-6-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- ( tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.32 (silica gel, methylene chloride / methanol - 96: 4)

Mass Spectrum (ESI⁺): m / z = 601 [M + H]⁺ (158) 1 - [([1,6] naphthyridin-5-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidine-1 -yl] -xanthine

Rf value: 0.20 (silica gel, ethyl acetate / methanol = 98: 2)

Mass Spectrum (ESI⁺): m / z = 559 [M + H]⁺ (159) 1 - [([1,8] naphthyridin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidine-1 -yl] -xanthine

Rf value: 0.12 (silica gel, ethyl acetate / methanol = 98: 2)

Mass Spectrum (ESI⁺): m / z = 559 [M + H]⁺ (160) 1 - [(4-fluoro-naphthalen-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) - 8- [(R) -3 - (tert-butyloxycarbonylamino) - piperidin-1-yl] -xanthine

Rf value: 0.47 (silica gel, petroleum ether / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z = 575 [M + H]⁺ (161) 1 - [([1,5] naphthyridin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [(R) -3 - (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.39 (silica gel, ethyl acetate)

Mass Spectrum (ESI⁺): m / z = 559 [M + H]⁺ (162) 1- [2- (3-methyl-2-oxo-2,3-dihydro-benzooksazol-4-yl) -2-oxo-ethyl] -3-methyl-7- (2butyn-1-yl) -8- [(7?) -3 - (tert-Butyloxycarbonylamino) -piperidin-1-yl] -xanthine Rf value: 0.60 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 606 [M + H]⁺ (163) 1 - [(8-phenyl-quinoxalin-6-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(7?) - 3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.48 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z - 356 [M + H]⁺ (164) 1- [([1,5] naphthyridin-4-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(7?) - 3- (tert-butyloxycarbonylamino) ) -piperidin-1-yl] -xanthine

Rf value: 0.25 (silica gel, ethyl acetate / petroleum ether = 4: 1)

Mass Spectrum (ESI⁺): m / z = 559 [M + H]⁺ (165) 1- ((E) -3-pentafluorophenyl-allyl) -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert-butyloxycarbonylamino) -piperidine-1 -yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 623 [M + H]⁺ (166) 1- [(E) -3- (2-Trifluoromethyl-phenyl) -allyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert-butyloxycarbonyl) lamino) -piperidin-1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 601 [M + H]⁺ (167) 1- [(E) -3- (3-Trifluoromethyl-phenyl) -allyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert-butyloxycarbonyl) lamino) -piperidin-1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 601 [M + H]⁺ (168) 1- [(E) -3- (4-Trifluoromethyl-phenyl) -allyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) - 3- ( tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 601 [M + H]⁺ (169) 1 - [(3-Trifluoromethyl-isoquinolin-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(7?) - 3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.68 (silica gel, cyclohexane / ethyl acetate = 3: 7)

Mass Spectrum (ESI⁺): m / z = 626 [M + H]⁺ (170) 1 - [(3-methyl-isoquinolin-1-yl) methyl] -3-methyl-7- (2-cyano-benzyl) -8-chloro-xanthine (171) 1 - [(3-difluoromethyl) isoquinolin-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(7β) -3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.38 (silica gel, cyclohexane / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z = 608 [M + H]⁺ (172) 1 - [(4-chloro-3-methoxy-isoquinolin-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) - piperidin-1-yl] -xanthine

Rf value: 0.65 (silica gel, methylene chloride / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z = 622, 624 [M + H]⁺ (173) 1 - [(4-ethoxy-quinazolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidine-1 - yl] -xanthine

Rf value: 0.25 (silica gel, methylene chloride / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z = 603 [M + H]⁺ (174) 1 - [(4-isopropyloxy-quinazolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidine-1- yl] -xanthine

Rf value: 0.40 (silica gel, methylene chloride / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z = 617 [M + H]⁺ (175) 1 - [(2-methyl-benzothiazol-6-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidine-1- yl] -xanthine

Rf value: 0.56 (silica gel, methylene chloride / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z = 578 [M + H]⁺ (176) 1 - [(3-phenyl-isoquinolin-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(7?) - 3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.75 (silica gel, methylene chloride / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z = 634 [M + H]⁺ (177) 1 - [(4-phenyloxy-quinazolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidine-1- yl] -xanthine

Rf value: 0.35 (silica gel, methylene chloride / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z = 651 [M + H]⁺ (178) 1 - [(4-Phenyl-quinazolin-2-yl) methyl] -3-cyclopropyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidine-1- yl] -xanthine

Rf value: 0.45 (silica gel, methylene chloride / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z = 661 [M + H]⁺ (179) 1 - [(3-Methyl-isoquinolin-1-yl) methyl] -3-cyclopropyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidine-1- yl] -xanthine

Rf value: 0.50 (silica gel, methylene chloride / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z = 598 [M + H]⁺ (180) 1- [2- (3-difluoromethoxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(7?) - 3- ( tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.77 (silica gel, methylene chloride / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z = 601 [M + H]⁺ (181) 1 - [(2-phenyl-quinazolin-4-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidine-1 - yl] -xanthine

Rf value: 0.65 (silica gel, methylene chloride / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z = 635 [M + H]⁺ (182) 1- [2- (2-methoxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidine -1-yl] -xanthine

Rf value: 0.57 (silica gel, methylene chloride / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z = 565 [M + H]⁺ (183) 1- [2- (3-methoxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidine 1-yl] -xanthine

Rf value: 0.63 (silica gel, methylene chloride / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z = 565 [M + H]⁺ (184) 1- [2- (3-Trifluoromethoxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(7?) - 3- ( tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.64 (silica gel, methylene chloride / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z = 619 [M + H]⁺ (185) 1- [2- (biphenyl-2-yl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(7?) - 3- ( tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.70 (silica gel, methylene chloride / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z = 611 [M + H]⁺ (186) 1- [2- (biphenyl-3-yl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert-butyloxycarbonyl) lamino) -piperidin-1-yl] -xanthine

Rf value: 0.75 (silica gel, methylene chloride / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z = 611 [M + H]⁺ (187) 1- [2- (3-Isopropyloxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert-butyloxycarbonyl) lamino) -piperidin-1-yl] -xanthine

Rf value: 0.66 (silica gel, methylene chloride / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z = 593 [M + H]⁺ (188) 1 - [(3-methyl-isoquinolin-1-yl) methyl] -3-cyclopropyl-7- (2-butyn-1-yl) -8 - [(7?) - 3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.50 (silica gel, methylene chloride / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z = 598 [M + H]⁺ (189) 1 - [(4-phenyl-quinazolin-2-yl) methyl] -3-cyclopropyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert-butyloxycarbonylamino) - piperidin-1-yl] -xanthine

Rf value: 0.50 (silica gel, methylene chloride / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z = 661 [M + H]⁺ (190) 1 - [(4-cyano-naphthalen-1-yl) methyl] -3-cyclopropyl-7- (2-butyn-1-yl) -8 - [(5) -3- (tert-butyloxycarbonylamino) - piperidin-1-yl] -xanthine

Rf value: 0.75 (silica gel, methylene chloride / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z = 608 [M + H]⁺ (191) 1- [2- (2-phenyloxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(5) -3- (tert-butyloxycarbonyl) lamino) -piperidin-1-yl] -xanthine

Rf value: 0.85 (silica gel, methylene chloride / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z = 627 [M + H]⁺ (192) 1- [2- (3-Ethoxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(5) -3- (tert-butyloxycarbonyl) lamino) -piperidin-1-yl] -xanthine

Rf value: 0.72 (silica gel, methylene chloride / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z = 579 [M + H]⁺ (193) 1- [2- (3-methoxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(5) -3- (tert-butyloxycarbonyl) lamino) -piperidin-1-yl] -xanthine

Rf value: 0.67 (silica gel, methylene chloride / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z = 565 [M + H]⁺ (194) 1- [2- (2-methoxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(5) -3- (tert-butyloxycarbonylamino) ) -piperidin-1-yl) -xanthine

Rf value: 0.57 (silica gel, methylene chloride / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z = 565 [M + H]⁺ (195) 1 - [(3-methyl-isoquinolin-1-yl) methyl] -3-methyl-7- (2-chloro-benzyl) -8-bromo-xanthine (196) 1 - [(3-methyl-benzyl) isoquinolin-1-yl) methyl] -3-methyl-7- (2-bromo-benzyl) -8 - [(5) -3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine (197) 1- [(1,2,3,4-tetrahydro-phenanthridin-6-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidine-1 Rf value: 0.55 (silica gel, ethyl acetate / petroleum ether = 2: 1)

Mass Spectrum (ESI⁺): m / z = 612 [M + H]⁺

Example VI 1- (2- {3 - [(methanesulfinyl) methoxy] phenyl} -2-oxoethyl) -3-methyl-7- (3-methyl-2-buten-1-yl) -813 - ( tert-butylox ycarbonylaminoj-piperidin-1-yl-xanthine

A solution of 402 mg of 1- (2- {3 - [(methylsulfanyl) methoxy] phenyl} -2-oxo-ethyl) -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-Butyloxycarbonylamino) -piperidin-1-yl] -xanthine in 10 ml of hexafluoroisopropanol is added 0.15 ml of a 35% hydrogen peroxide solution. The reaction mixture is stirred for half an hour at ambient temperature. Then 5 ml of a 10% sodium thiosulfate solution is added. The aqueous phase is extracted twice with 5 ml of methylene chloride. The combined extracts are dried over sodium sulfate and evaporated. The yellow residue is purified by chromatography through a silica gel column with cyclohexane / ethyl acetate / methanol (5: 4: 1) as the eluent.

Yield: 299 mg (73% of theoretical value)

Rf value: 0.28 (silica gel, cyclohexane / ethyl acetate / methanol = 5: 4: 1)

Mass Spectrum (ESI⁺): m / z = 643 [M + H]⁺

The following compounds are obtained analogously to Example VI:

(1) 1- [2- (3-Methanesulfonyl-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) - 8- [3- (tert-butyloxycarbonyl) lamino) -piperidin-1-yl] -xanthine

Rf value: 0.05 (silica gel, ethyl acetate / cyclohexane = 3: 1)

Mass Spectrum (ESI⁺): m / z = 613 [M + H]⁺ (2) 1- (2- {2 - [(methanesulfonyl) methoxy] phenyl} -2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8- [3 (tert) -butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 627 [M + H]⁺

Example VII

- [(2-trimethylsilanyl-ethoxy) methyl] -7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidin-1-yl-xanthine

236 µl of 1,8-diazabicyclo [5.4.0] undec-7-one is added dropwise to 630 mg of 7- (3-methyl-2-butenl-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidine -l-yl] -xanthine in 11 ml of acetonitrile. The solution is stirred for two hours at ambient temperature and then the acetonitrile is distilled off under vacuum. The flask residue is taken up in 11 ml of Ν, Ν-dimethylformamide and is combined with 258 mg (2-trimethylsilanyl-ethoxy) methyl chloride. The reaction mixture is stirred for three hours at 120 ° C. For work up, water is added, the formed precipitate is filtered off and taken up in ethyl acetate. The solution is dried over magnesium sulfate, evaporated and chromatographed through a silica gel column with cyclohexane / ethyl acetate / methanol (6: 1: 0 to 0: 5: 1) as eluent.

Yield: 435 mg (53% of theoretical value)

Mass Spectrum (ESI⁺): m / z = 549 [M + H]⁺

The following compounds are obtained analogously to Example VII:

(1) 3 - [(2-trimethylsilanyl-ethoxy) methyl] -7- (2-cyano-benzyl) -xanthine

Mass Spectrum (ESL): m / z = 396 [MH] '(2) 3 - [(methoxycarbonyl) methyl] -7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butyloxycarbonylamino) ) -piperidin-1-yl] -xanthine

Rf value: 0.31 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 491 [M + H]⁺

Example Wine

7- (3-Methyl-2-buten-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

510 mg of potassium tert-butoxide is added to 2.32 g of 2- [3- (tert-butyloxycarbonylamino) piperidin-1-yl] -3- (3-methyl-2-buten-1-yl) -4-ethoxycarbonyl 5- {[(ethoxycarbonylamino) carbonyl] amino} -3 H -imidazole in 35 ml ethanol. The yellow solution is refluxed for five hours. After cooling to ambient temperature, it is diluted with methylene chloride. The organic phase is washed with saturated ammonium chloride solution and saturated sodium chloride solution, dried over magnesium sulfate and evaporated. The crude product is purified by chromatography through a silica gel column with methylene chloride / methanol / conc. methanolic ammonia (95: 5: 1 to 90: 10: 1) as eluent.

Yield: 630 mg (35% of theoretical value)

Rf value: 0.24 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 419 [M + H]⁺

Example IX

2- [3- (tert-Butyloxycarbonylamino) -piperidin-1-yl] -3- (3-methyl-2-buten-1-yl) -4-ethoxycarbonyl-5- {ylethoxycarbonylamino carbonylaminol-3/7-imidazole

2.97 ml of ethyl isocanatoformate is added to 4.00 g of 2- [3- (tert-butyloxycarbonylamino) piperidin-1-yl] -3- (3-methyl-2-buten-1-yl) -4-ethoxycarbonyl-5 -amino-3 H -imidazole in 90 ml of 1,2-dimethoxyethane and the light brown solution is heated overnight at 120 ° C in an oil bath. Then an additional 0.6 ml of ethyl isocyanato formate is added and heating is continued for a further four hours. For working up, the reaction mixture is combined with saturated potassium carbonate solution and extracted with ethyl acetate. The organic phase is dried over magnesium sulfate, evaporated and purified through a silica gel column with methylene chloride / methanol / conc. methanolic ammonia (98: 2: 1 to 90: 10: 1) as eluent.

Yield: 2.27 g (45% of theoretical value)

Rf value: 0.29 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 537 [M + H]⁺

Example X

2- [3- (tert-butyloxycarbonylamino) -piperidin-l-yl] -3- (3-methyl-2-butene-l-yl) -4etoksvkarbonyl-5-amino-377-imidazole

Prepared by refluxing cyanimino- [N- (3-methyl-2-buten-1-yl) -N (ethoxycarbonylmethyl) amino] - [3- (tert-butyloxycarbonylamino) -piperidin-1-yl] methane with sodium in ethanol.

Rf value: 0.26 (alumina, ethyl acetate / petroleum ether = 8: 2)

Mass Spectrum (ESI⁺): m / z = 422 [M + H]⁺

Example XI

Cyanimino- [N- (3-methyl-2-buten-1-yl) -N- (ethoxycarbonylmethyl) amino] - [3- (tert-butyloxycarbonylamino) -piperidin-1-yl-methane

Prepared by reacting cyanimino- [N- (3-methyl-2-buten-1-yl) -N- (ethoxycarbonylmethyl) amino] phenyloxymethane with 3- (tert-butyloxycarbonylamino) -piperidine in the presence of potassium carbonate in Ν, Ν-dimethylformamide at ambient temperature.

Rf value: 0.10 (silica gel, petroleum ether / ethyl acetate = 6: 4)

Mass Spectrum (ESI⁺): m / z = 422 [M + H]⁺

Example XII

Cyanimino-ΓΝ- (3-methyl-2-buten-1-yl) -N- (ethoxycarbonylmethyl-amino) -phenylox-methane

Prepared by reaction of cyanimino - [(ethoxycarbonylmethyl) amino] -phenyloxymethane with 1-bromo-3-methyl-2-butene in the presence of potassium carbonate in acetone at ambient temperature.

Rf value: 0.70 (silica gel, cyclohexane / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z = 316 [M + H]⁺

Example ΧΙΠ

Cyanimino-1 (ethoxycarbonylmethyl) aminol-phenyloxy-methane

Prepared by reaction of diphenyl cyanocarbonimidate with ethyl amino acetate hydrochloride in the presence of triethylamine in isopropanol at ambient temperatu re (analogous to R. Besse et al., Tetrahedron 1990, 46, 7803-7812).

Rf value: 0.73 (silica gel, petroleum ether / ethyl acetate = 8: 2)

Mass Spectrum (ESI⁺): m / z = 248 [M + H]⁺

Example XIV (1-Methyl-3- (methoxycarbonyl) methyl-7- (2-cyano-benzyl) -8-chloro-xanthine

Prepared by reaction of 1-methyl-7- (2-cyano-benzyl) -8-chloro-xanthine with methyl bromoacetate in the presence of potassium carbonate in Ν, Ν-dimethylformamide at ambient temperature.

Rf value: 0.80 (silica gel, methylene chloride / methanol = 9: 1)

Mass Spectrum (ESI⁺): m / z = 388, 390 [M + H]⁺

The following compounds are obtained analogously to Example XIV:

(1) 1-Methyl-3-cyanomethyl-7- (2-cyano-benzyl) -8-chloro-xanthine

Mass Spectrum (ESI⁺): m / z = 355, 357 [M + H]⁺ (2) 1-Methyl-3- (2-propyn-1-yl) -7- (2-cyano-benzyl) -8-chloro-xanthine

R f value: 0.80 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 354, 356 [M + H]⁺ (3) 1-Methyl-3- (2-propen-1-yl) -7- (2-cyano-benzyl) -8-chloro-xanthine

Rf value: 0.90 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 356, 358 [M + H]⁺ (4) 1- (2-Phenyl-2-oxo-ethyl) -3-cyanomethyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidine-1 -yl] -xanthine

Rf value: 0.78 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass spectrum (ESI⁺): m / z = 576 [M + H]⁺ (5) 1-Methyl-3-isopropyl-7- (2-cyano-benzyl) -8-chloro-xanthine

Mass Spectrum (ESI⁺): m / z = 358, 360 [M + H]⁺

Example XV 1-Methyl-7- (2-cyano-benzyl) -8-chloro-xanthine

Prepared by treating 1-methyl-3 - [(2-trimethylsilanyl-ethoxy) methyl] -7- (2-cyanobenzyl) -8-chloro-xanthine with trifluoroacetic acid in methylene chloride at ambient temperature. Rf value: 0.50 (silica gel, methylene chloride / methanol = 9: 1)

Mass Spectrum (ESI⁺): m / z = 316, 318 [M + H]⁺

The following compounds are obtained analogously to Example XV:

(1) 1- (2-Phenyl-2-oxo-ethyl) -3-methyl-8-bromo-xanthine

Rf value: 0.26 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI '): m / z = 361, 363 [MH]' (2) 1 - [(4-oxo-3,4-dihydro-phthalazin-1-yl) methyl] -3-methyl-7- ( 3-Methyl-2-buten-1-yl) -8- (3 amino-piperidin-1-yl) -xanthine (Since the compound still contains impurities that cannot be removed by chromatography, the material is again converted to the BOC-protected derivative and then purified by chromatography, cf. Ex. XXV (1).)

Mass Spectrum (ESI⁺): m / z = 491 [M + H]⁺

Example XVI

1- methyl-3- (2-trimethylsilanyl-ethoxy) methyl-7- (2-cyano-benzyl) -8-chloro-xanthine Prepared by chlorination of 1-methyl-3 - [(2-trimethylsilanyl-ethoxy) methyl ] -7- (2-cyano-benzyl) xanthine with N-chlorosuccinimide in dichloroethane under reflux.

Mass Spectrum (EI): m / z = 445, 447 [M]⁺

Example XVII

7- (2-cyano-benzyl) -xanthine

Prepared by treating 16.68 g of 2-amino-7- (2-cyano-benzyl) -1,7-dihydro-purin-6-one with 17.00 g of sodium nitrite in a mixture of 375 ml of conc. acetic acid, 84 ml water and 5.2 ml conc. hydrochloric acid at 50 ° C.

Yield: 8.46 g (50% of theoretical value)

Mass Spectrum (ESI⁺): m / z = 268 [M + H]⁺

Example XVHI

2- amino-7- (2-cyano-benzyl) -1.7-dihydro-purin-6-one

Prepared by reaction of 20.00 g of guanosine hydrate with 22.54 g of 2-cyano-benzyl bromide in dimethyl sulfoxide at 60 ° C and subsequent treatment with 57 ml of conc. hydrochloric acid.

Yield: 18.00 g (97% of theory)

Mass Spectrum (ESI⁺): m / z = 267 [M + H]⁺

Example XIX

- {2- [3- (2-oxo-imidazolidin-1-yl) -phenyl] -2-oxo-ethyl} -3-methyl-7- (3-methyl-2-buten-1-yl) 8 - 13 - (tert-butyloxycarbonylaminoj-piperidin-1-yl) xanthine

Prepared by treating 1- [2- (3 - {[(2-chloro-ethylamino) carbonyl] amino} -phenyl) -2-oxoethyl] -3-methyl-7- (3-methyl-2-butene-1 -yl) -8- [3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine with potassium tert-butoxide in Ν, Ν-dimethylformamide at ambient temperature. Rf value: 0.50 (silica gel, methylene chloride / methanol = 9: 1)

Example XX

- [2- (3 - {[(2-chloro-ethylamino) carbonyl] amino} -phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2butene-1-yl) - 8 -13 - (tert-Butyloxycarbonylamino) -piperidin-1-yl-xanthine

Prepared by reaction of 221 mg of 1- [2- (3-amino-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl2-buten-1-yl) -8- [3- ( tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine with 60 μΐ of 2-chloroethyl isocyanate in 3 ml of methylene chloride at ambient temperature.

Yield: 163 mg (64% of theoretical value)

Rf value: 0.20 (silica gel, cyclohexane / ethyl acetate / methanol = 6: 3: 1)

Mass Spectrum (ESI⁺): m / z = 671, 673 [M + H]⁺

The following compounds are obtained analogously to Example XX:

(1) 1- [2- (2- {[(ethoxycarbonylamino) carbonyl] amino} -phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) - 8- [3- (tert-Butyloxycarbonylamino) -piperidin-1-yl] -xanthine (Made in Ν, Ν-dimethylformamide at 30 ° C)

Rf value: 0.26 (silica gel, cyclohexane / ethyl acetate = 4: 6)

Mass Spectrum (ESI⁺): m / z = 681 [M + H]⁺

Example XXI 1- [2- (3-Amino-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butyloxycarbonylaminol) piperidin-1-yl-xanthine

Prepared by the treatment of 1- [2- (3-nitrophenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-butenl-yl) -8- [3- (tert. butyloxycarbonylamino) -piperidin-1-yl] -xanthine with powdered iron in a mixture of ethanol, water and glacial acetic acid (80:25:10) at 100 ° C.

Rf value: 0.55 (silica gel, cyclohexane / ethyl acetate / methanol / conc. Aqueous ammonia = 50: 30: 20: 1)

Mass Spectrum (ESI⁺): m / z = 566 [M + H]⁺

The following compounds are obtained analogously to Example XXI:

(1) 1- [2- (2-Amino-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten -1-yl) -8- [3- ( tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 566 [M + H]⁺ (2) 1- [2- (2-Amino-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8 - [(5) - 3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z - 566 [M + H]⁺ (3) 1 - [(5-amino-isoquinolin-1-yl) methyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butyloxycarbonylamino) - piperidin-1-yl] -xanthine

Rf value: 0.22 (silica gel, ethyl acetate)

Mass Spectrum (ESI⁺): m / z = 589 [M + H]⁺ (4) 1- [2- (2-Amino-phenyl) -2-oxo-ethyl] -3-methyl-7 - [(1-cyclopenten-1-yl) methyl] -8-bromoxanthine

Mass Spectrum (ESI⁺): m / z = 458, 460 [M + H]⁺ (5) 1- [2- (2-Amino-phenyl) -2-oxo-ethyl] -3-methyl-7 - ((E) -2-buten-1-yl) -8-bromo-xanthine (the product contains about 10% Z isomer)

Rf value: 0.55 (silica gel, cyclohexane / ethyl acetate = 4: 6)

Mass Spectrum (ESI⁺): m / z = 432, 434 [M + H]⁺ (6) 1- [2- (2-amino-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8-bromo-xanthine Rf value: 0, 50 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 430, 432 [M + H]⁺ (7) 1- [2- (2-Amino-phenyl) -2-oxo-ethyl] -3-methyl-7 - ((E) -2-buten-1-yl) -8 - [(7?) -3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 552 [M + H]⁺ (8) 1- [2- (2-Amino-phenyl) -2-oxo-ethyl] -3-methyl-7 - ((E) -2-buten-1-yl) -8- [(5) - 3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 552 [M + H]⁺ (9) 1- [2- (2-Amino-3-methoxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [ 3 (tert-Butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.82 (silica gel, ethyl acetate / petroleum ether = 4: 1)

Mass Spectrum (ESI⁺): m / z = 596 [M + H]⁺

Example XXII

1- (2- {2 - [(Ethylcarbonyl) amino] -phenyl} -2-oxo-ethyl) -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3 ( tert-butyloxycarbonylaminoj-piperidin-1-yl-xanthine

Prepared by reaction of 248 mg of 1- [2- (2-amino-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl2-buten-1-yl) -8- [3- (tert -butyloxycarbonylamino) -piperidin-1-yl] -xanthine with 40 μΐ propionic acid chloride in the presence of 60 μΐ pyridine in Ν, Ν-dimethylformamide at 80 ° C.

Yield: 168 mg (62% of theoretical value)

Rf value: 0.55 (silica gel, cyclohexane / ethyl acetate = 3: 7)

Mass Spectrum (ESI⁺): m / z = 622 [M + H]⁺

The following compounds are obtained analogously to Example ΧΧΠ:

(1) 1- ({5- [(methoxycarbonyl) methylamino] -isoquinolin-1-yl} methyl) -3-methyl-7- (3-methyl-2butene-1-yl) - 8- [3- (tert -butyloxycarbonylamino) -piperidin-1-yl] -xanthine (Made with methyl bromoacetate and potassium carbonate)

Rf value: 0.42 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 661 [M + H]⁺ (2) 1- [2- (2-Acetylamino-phenyl) -2-oxo-ethyl] -3-methyl-7 - ((E) -2-buten-1-yl) -8- [3- (tert-butyloxycarbonyl) lamino) -piperidin-1-yl] -xanthine (the product contains about 10% Z-isomer)

Mass Spectrum (ESI⁺): m / z = 594 [M + H]⁺ (3) 1- (2- {2 - [(isopropylcarbonyl) amino] phenyl} -2-oxoethyl) -3-methyl-7 - ((E) -2-buten-1-yl) 8- [3- (tert-Butyloxycarbonylamino) -piperidin-1-yl] -xanthine (the product contains about 10% Z-isomer)

Mass Spectrum (ESI⁺): m / z = 622 [M + H]⁺ (4) 1- [2- (2-Acetylamino-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8 - [(5) - 3 (tert-Butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.50 (silica gel, cyclohexane / ethyl acetate = 3: 7)

Mass Spectrum (ESI⁺): m / z = 608 [M + H]⁺ (5) 1- [2- (2-Acetylamino-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidine -1-yl] -xanthine

Rf value: 0.34 (silica gel, cyclohexane / ethyl acetate = 3: 7)

Mass Spectrum (ESI⁺): m / z = 592 [M + H]⁺ (6) 1- (2- {2 - [(isopropylcarbonyl) amino] -phenyl} -2-oxo-ethyl) -3-methyl-7- (3-methyl-2-butenyl) -8- [3 - (tert-butyloxycarbonylamino) -piperidin-l-yl] -xanthine

Rf value: 0.25 (silica gel, cyclohexane / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z = 636 [M + H]⁺ (7) 1- (2- {2 - [(isopropylcarbonyl) amino] phenyl} -2-oxoethyl) -3-methyl-7- (2-butyn-1-yl) -8 [3- (tert (butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.44 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 620 [M + H]⁺ (8) 1- [2- (2-Acetylamino-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(5) -3- (tert-butyloxycarbonyl) lamino) -piperidin-1-yl] -xanthine

Rf value: 0.34 (silica gel, cyclohexane / ethyl acetate = 3: 7)

Mass Spectrum (ESI⁺): m / z = 592 [M + H]⁺ (9) 1- (2- {2 - [(Isopropylcarbonyl) amino] -phenyl} -2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8 [(* S) -3- (tert-butyloxycarbonylamino) -piperidin-l-yl] -xanthine

Rf value: 0.44 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 620 [M + H]⁺ (10) 1- (2- {2 - [(methoxycarbonyl) amino] phenyl} -2-oxo-ethyl) -3-methyl-7- (3-methyl-2-buten1-yl) -8- [3 - (tert-Butyloxycarbonylamino) -piperidin-1-yl] -xanthine (Made in acetonitrile at 55 ° C)

Rf value: 0.25 (silica gel, cyclohexane / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z = 624 [M + H]⁺ (11) 1- (2- {2 - [(isopropylcarbonyl) amino] -phenyl} -2-oxo-ethyl) -3-methyl-7 - ((E) -2-buten-110-yl) -8- [ (5) -3- (tert-Butyloxycarbonylamino) -piperidin-1-yl] -xanthine (Performed in acetonitrile at 65 ° C)

Rf value: 0.50 (silica gel, cyclohexane / ethyl acetate / isopropanol = 14: 3: 3)

Mass Spectrum (ESI⁺): m / z = 622 [M + H]⁺ (12) 1- (2- {2 - [(Ethylcarbonyl) amino] -phenyl} -2-oxo-ethyl) -3-methyl-7 - ((E) -2-buten-1-yl) -8 [ (5) -3 - (tert-Butyl oxycarbonylamino) -piperidin-1-yl] -xanthine Mass Spectrum (ESI⁺): m / z - 608 [M + H]⁺ (13) 1- [2- (2-Acetylamino-phenyl) -2-oxo-ethyl] -3-methyl-7 - ((E) -2-buten-1-yl) -8 - [(5) - 3- (tert-Butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 594 [M + H]⁺ (14) 1- [2- (2-acetylamino-phenyl) -2-oxo-ethyl] -3-methyl-7 - ((E) -2-buten-1-yl) -8- [(5) - 3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.28 (silica gel, cyclohexane / ethyl acetate / isopropanol = 8: 1: 1)

Mass Spectrum (ESI⁺): m / z = 594 [M + H]⁺ (15) 1- (2- {2 - [(isopropylcarbonyl) amino] phenyl} -2-oxoethyl) -3-methyl-7- (2-butyn-1-yl) -8 [(5) - 3- (tert -butyl oxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.90 (silica gel, methylene chloride / methanol = 9: 1) (16) 1- (2- {2 - [(isopropylcarbonyl) amino] phenyl} -2-oxoethyl) -3-methyl 7 - ((E) -2-Butenyl) -8 - [(5) -3- (tert-Butyloxycarbonylamino) -piperidin-1-yl] xanthine (Performed in 1,2-dichloroethane at 45 ° C )

Rf value: 0.30 (silica gel, cyclohexane / ethyl acetate / isopropanol = 8: 1: 1)

Mass Spectrum (ESI⁺): m / z = 622 [M + H]⁺ (17) 1- (2- {2 - [(Ethylcarbonyl) amino] phenyl} -2-oxo-ethyl) -3-methyl-7 - ((E) -2-buten-1-yl) -8 [ (S) -3- (tert-butyloxycarbonylamino) -piperidin-l-yl] -xanthine

Rf value: 0.48 (silica gel, cyclohexane / ethyl acetate / isopropanol = 14: 3: 3)

Mass Spectrum (ESI⁺): m / z = 608 [M + H]⁺ (18) 1- (2- {2 - [(Ethylcarbonyl) amino] phenyl} -2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8 - [(7? ) -3 (tert-Butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 606 [M + H]⁺ (19) 1- (2- {2 - [(Ethylcarbonyl) amino] phenyl} -2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8 - [(S) -3 (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.22 (silica gel, methylene chloride / methanol = 95: 5) (20) 1- (2- {2 - [(phenylcarbonyl) amino] phenyl} -2-oxoethyl) -3-methyl 7 - ((E) -2-Buten-1-yl) -8 [3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.55 (silica gel, cyclohexane / ethyl acetate / isopropanol = 14: 3: 3)

Mass Spectrum (ESI⁺): m / z = 656 [M + H]⁺ (21) 1- (2- {2- [(cyclopropylcarbonyl) amino] phenyl} -2-oxo-ethyl 1) -3-methyl-7- [(1 cyclopenten-1-yl) methyl] -8- [ 3- (tert-Butyloxycarbonylamino) -piperidin-1-yl] -xanthine (Performed with Hinig base and 4-dimethylamino-pyridine in methylene chloride)

Rf value: 0.60 (silica gel, methylene chloride / methanol = 18: 1)

Example ΧΧΠΙ

- (2- {3 - [(methoxycarbonyl) methoxy] -phenyl} -2-oxo-ethyl) -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino) piperidin-1-yl) -xanthine

Prepared by treating 1- (2- {3 - [(methoxycarbonyl) methoxy] phenyl} -2-oxo-ethyl) -3-methyl-7- (3-methyl-2-buten-1-yl) -8- 3- (tert-Butyloxycarbonylamino) -piperidin-1-yl] -xanthine with trifluoroacetic acid in methylene chloride at ambient temperature.

Mass Spectrum (ESI⁺): m / z = 539 [M + H]⁺

The following compounds are obtained analogously to Example ΧΧΠΙ:

(1) 1- (2- {2 - [(methoxycarbonyl) methoxy] phenyl} -2-oxoethyl) -3-methyl-7- (3-methyl-2-buten1-yl) -8- (3 -amino-piperidin-1-yl) -xanthine Mass Spectrum (ESI⁺): m / z = 539 [M + H]⁺

Example XXIV 1-Methyl-3-phenyl-7- (2-cyano-benzyl) -8-chloro-xanthine

A mixture of 829 mg of 1-methyl-7- (2-cyano-benzyl) -8-chloro-xanthine, 640 mg of phenylboronic acid, 509 mg of anhydrous copper acetate and 0.43 ml of pyridine in 20 ml of methylene chloride is stirred for four days at ambient temperature in the presence of 100 mg 4Å molecular sieves. Then an additional 320 mg of phenylboronic acid is added and the reaction mixture is stirred for a further day at ambient temperature. For working up, the mixture is filtered through talc and washed with ethyl acetate. The filtrate is evaporated and chromatographed through a silica gel column with cyclohexane / ethyl acetate (7: 3 to 1: 1) as the eluent.

Yield: 142 mg (14% of theoretical value)

Mass Spectrum (ESI⁺): m / z = 392, 394 [M + H]⁺

Example XXV 1- (2-Phenyl-2-oxo-ethyl) -7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butyloxycarbonylamino) piperidine-1- xanthine

Prepared by reacting 1- (2-phenyl-2-oxo-ethyl) -7- (3-methyl-2-buten-1-yl) -8- (3-aminopiperidin-1-yl) -xanthine with di- tert-butyl pyrocarbonate in the presence of Hunig base in methylene chloride at ambient temperature.

Rf value: 0.27 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1)

The following compounds are obtained analogously to Example XXV:

(1) 1 - [(4-oxo-3,4-dihydro-phthalazin-1-yl) methyl] -3-methyl-7- (3-methyl-2-buten-1-yl) - 8 - [ 3 (tert-Butyloxycarbonylamino) -piperidin-1-yl] -xanthine Rf value: 0.27 (silica gel, methylene chloride / methanol = 95: 5)

100

Mass Spectrum (ESI⁺): m / z = 591 [M + H]⁺ (2) 7-Acetyl-1- (tert-butyloxycarbonyl) -1,7-indole

Rf value: 0.82 (silica gel, methylene chloride / petroleum ether / ethyl acetate = 5: 4: 1)

Mass Spectrum (ESI⁺): m / z = 260 [M + H]⁺

Example XXVI 1 - [(Cinnolin-4-yl) methyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8-chloro-xanthine and 1 - [(1,4 dihydro-cinnoline) -4-ylmethyl-3-methyl-7- (3-methyl-2-buten-1-yl) -8-chloro-xanthine

510 mg of a mixture of (cinnolin-4-yl) -methanol and (1,4-dihydro-cinnolin-4-yl) -methanol (see Ex. XXVII) is added to 830 mg of 3-methyl-7- (3- methyl 2-buten-1-yl) -8-chloro-xanthine and 1.25 g of triphenylphosphine in 25 ml of tetrahydrofuran. The reaction mixture is combined with 0.92 ml of diethyl azodicarboxylate and stirred overnight at ambient temperature. Then it is evaporated and chromatographed through a silica gel column with ethyl acetate / petroleum ether (7: 3 to 0: 1) as eluent. A mixture of cinnoline and 1,4-dihydro-cinnoline compound is obtained.

Yield: 660 mg (52% of theoretical value)

Rf value: 0.60 (silica gel, ethyl acetate / petroleum ether = 7: 3)

The following compounds are obtained analogously to Example XXVI:

(1) 1- ({4-Oxo-3 - [(2-trimethylsilanyl-ethoxy) methyl] -3,4-dihydro-phthalazin-1-yl} methyl) -3-methyl-7- (3-methyl-2- butene-l-yl) -8-chloro-xanthine

Rf value: 0.85 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 557, 559 [M + H]⁺ (2) 1 - [(isoquinolin-3-yl) methyl] -3-methyl 1-7- (3-methyl 1-2-buten-1-yl) - 8-chloro-xanthine

Melting point: 194-195 ° C

Mass Spectrum (ESI⁺): m / z = 410, 412 [M + H]⁺ (3) 1 - [(3-methyl-4-oxo-3,4-dihydro-phthalazin-1-yl) methyl] -3-methyl-7- (3-methyl-2-buten-1-yl) 8 chloro-xanthine

Rf value: 0.66 (silica gel, ethyl acetate)

101

Mass Spectrum (ESI⁺): m / z = 441, 443 [M + H]⁺ (4) 1 - [(Quinolin-4-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8-bromo-xanthine (Performed with potassium carbonate)

Rf value: 0.45 (silica gel, ethyl acetate)

Mass Spectrum (ESI⁺): m / z = 438, 440 [M + H]⁺ (5) 1 - [(isoquinolin-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8-bromo-xanthine

Rf value: 0.78 (silica gel, ethyl acetate)

Mass Spectrum (ESI⁺): m / z = 438, 440 [M + H]⁺ (6) 1 - [(4-Dimethylamino-naphthalen-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidine-1- yl] -xanthine

Rf value: 0.80 (silica gel, ethyl acetate)

Mass Spectrum (ESI⁺): m / z = 600 [M + H]⁺ (7) 1 - [(isoquinolin-1-yl) methyl] -3-methyl-7 - ((E) -2-buten-1-yl) -8-bromo-xanthine (The product contains about 20% Z- isomer)

Rf value: 0.71 (silica gel, ethyl acetate)

Mass Spectrum (ESI⁺): m / z = 440, 442 [M + H]⁺ (8) 1 - [(1-methyl-1 H -indol-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8-bromo-xanthine Rf value: 0 95 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 440, 442 [M + H]⁺ (9) 1 - [(Quinolin-3-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8-bromo-xanthine

Rf value: 0.55 (silica gel, ethyl acetate / petroleum ether = 8: 2)

Mass Spectrum (ESI⁺): m / z = 438, 440 [M + H]⁺ (10) 1- {[1- (tert-Butyloxycarbonylamino) -1H- indol-2-yl] methyl} -3-methyl-7- (2-butyn-1-yl) 8-bromo-xanthine

Rf value: 0.74 (silica gel, petroleum ether / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z = 526, 528 [M + H]⁺

102 (11) 1- ({2-Methyl-1 - [(2-trimethylsilanyl-ethoxy) methyl] -1H-benzoimidazol-5-yl} methyl) -3-methyl-7- (2-butyn-1-yl) -8-Bromo-xanthine (mixed with 1- ({2-methyl-3 - [(2-trimethylsilanylethoxy) methyl] -3 / 7-benzoimidazol-5-yl} methyl) -3-methyl-7- (2- butyn-1-yl) -8-bromo-xanthine Mass Spectrum (ESI⁺): m / z = 571, 573 [M + H]⁺ (12) 1 - [(1 - [(2-trimethylsilanyl-ethoxy) methyl] -1,7-benzoimidazol-5-yl) methyl] -3-methyl-7- (2butyn-1-yl) -8-bromo -xanthine (mixed with 1 - [(3 - [(2-trimethylsilanyl-ethoxy) methyl] -377benzoimidazol-5-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8-bromo xanthine)

Rf value: 0.50 (silica gel, methylene chloride / methanol - 95: 5)

Mass Spectrum (ESI⁺): m / z = 557, 559 [M + H]⁺ (13) 1 - [(pyrazolo [1,5-a] pyridin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8-bromo-xanthine Rf value: 0 (Silica gel, petroleum ether / ethyl acetate = 1: 2)

Mass Spectrum (ESI⁺): m / z = 427, 429 [M + H]⁺

Example XXVII (Cinnolin-4-yl) -methanol and (1,4-dihydro-cinnolin-4-yl) -methanol

A solution of 1.00 g of methylcinnoline-4-carboxylate in 15 ml of diethyl ether is added dropwise at 0 ° C to a suspension of 222 mg of lithium aluminum hydride in 5 ml of diethyl ether. After 1.5 hours, water is gently added dropwise to the reaction mixture which is stirred with methylene chloride and suction filtered through a glass fiber filter. The aqueous phase is extracted with methylene chloride and the combined organic phases are dried over magnesium sulfate and evaporated. According to 1-NMR, the mixture of cinnoline and 1,4-dihydro-cinnoline compound is obtained as a yellow oil and it is reacted further without further purification.

Yield: 530 mg (62% of theoretical value)

Rf value: 0.63 (silica gel, ethyl acetate)

Mass Spectrum (ESI⁺): m / z = 161 [ML + H]⁺ and 163 [M2 + H]⁺

103

The following compounds are obtained analogously to Example XXVII:

(1) {2-Methyl-1 - [(2-trimethylsilanyl-ethoxy) methyl] -1,7-benzoimidazol-5-yl} -methanol (mixed with {2-methyl-3 - [(2-trimethylsilanyl-ethoxy) ) methyl] -3 / f-benzoimidazol-5-yl} methanol)

Mass Spectrum (ESI⁺): m / z = 293 [M + H]⁺ (2) (2,3,8-trimethyl-quinoxalin-6-yl) -methanol

Rf value: 0.45 (silica gel, petroleum ether / ethyl acetate = 1: 2)

Mass Spectrum (ESI⁺): m / z - 203 [M + H]⁺ (3) (8-methyl-quinoxalin-6-yl) -methanol

Rf value: 0.18 (silica gel, cyclohexane / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z = 175 [M + H]⁺ (4) (E) -3-pentafluorophenyl-2-propen-1-ol (Done with diisobutylaluminum hydride in toluene)

Mass Spectrum (EI): m / z = 224 [M]⁺ (5) (E) -3- (2-Trifluoromethyl-phenyl) -2-propen-1-ol (Done with diisobutylaluminum hydride in toluene) (6) (E) -3 - (3-Trifluoromethyl-phenyl) -2- propene-1-ol (Made with diisobutylaluminum hydride in toluene)

Mass Spectrum (EI): m / z = 202 [M]⁺ (7) (E) -3- (4-Trifluoromethyl-phenyl) -2-propen-1-ol (Done with diisobutylaluminum hydride in toluene)

Example XXVIII

4-Hydroxymethyl-2- (2-trimethylsilanyl-ethoxy) methyl -2H-phthalazin-1-one

Prepared by treating methyl 4-oxo-3 - [(2-trimethylsilanyl-ethoxy) methyl] -3,4-dihydrophthalazine-1-carboxylate with sodium borohydride in tetrahydrofuran at 40 ° C.

104

Rf value: 0.55 (silica gel, cyclohexane / ethyl acetate 1: 1)

Mass Spectrum (ESI⁺): m / z = 307 [M + H]⁺

The following compounds are obtained analogously to Example XXVIII:

(1) (3,4-Dimethyl-isoquinolin-1-yl) -methanol (Performed with lithium borohydride in tetrahydrofuran)

Rf value: 0.35 (silica gel, petroleum ether / ethyl acetate = 2: 1)

Mass Spectrum (ESI⁺): m / z = 188 [M + H]⁺ (2) (3-Methyl-imidazo [1,2-a] pyridin-2-yl) -methanol (Performed with lithium borohydride in tetrahydrofuran)

Rf value: 0.48 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 163 [M + H]⁺ (3) (3,4-Dimethyl-6,7-dihydro-5 H - [2] pyrindin-1-yl) -methanol (Performed with lithium borohydride in tetrahydrofuran)

Rf value: 0.40 (alumina, petroleum ether / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z = 178 [M + H]⁺ (4) (3,4-Dimethyl-5,6,7,8-tetrahydro-isoquinolin-1-yl) -methanol (Performed with lithium borohydride in tetrahydrofuran)

Rf value: 0.45 (alumina, petroleum ether / ethyl acetate = 3: 1)

Mass Spectrum (ESI⁺): m / z = 192 [M + H]⁺ (5) 6-hydroxymethyl-1,2,3,4-tetrahydro-phenanthridine (Performed with lithium borohydride in tetrahydrofuran at ambient temperature)

Rf value: 0.40 (silica gel, petroleum ether / ethyl acetate = 2: 1)

Mass Spectrum (ESI⁺): m / z = 214 [M + H]⁺

105

Example XXIX

Methyl 4-oxo-3- (2-trimethylsilanyl-ethoxy) methyl -3,4-dihydro-phthalazine-1-carboxylate

Prepared by reaction of methyl 4-oxo-3,4-dihydro-phthalazine-1-carboxylate with (2-trimethylsilanyl-ethoxy) methyl chloride in the presence of Hunig base in methylene chloride at ambient temperature.

Rf value: 0.75 (silica gel, cyclohexane / ethyl acetate 6: 4)

Mass Spectrum (ESI⁺): m / z = 335 [M + H]⁺

The following compounds are obtained analogously to Example XXIX:

(1) 7-Acetyl-3 - [(2-trimethylsilanyl-ethoxy) methyl] -3β-benzooksazol-2-one

Mass Spectrum (ESI⁺): m / z = 308 [M + H]⁺ (2) 4-Acetyl-3 - [(2-trimethylsilanyl-ethoxy) methyl] -3 H -benzoxazol-2-one

Rf value: 0.87 (silica gel, methylene chloride / methanol = 99: 1) (3) 4-acetyl-1,3-bis - [(2-trimethylsilanyl-ethoxy) methyl] -1,3-dihydro-benzoimidazole 2-one (Made with potassium tert-butoxide in Ν, Ν-dimethylformamide)

Rf value: 0.90 (silica gel, petroleum ether / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z = 437 [M + H]⁺ (4) 6-methyl-1 - [(2-trimethylsilanyl-ethoxy) methyl] -1H-quinolin-2-one

Rf value: 0.78 (silica gel, petroleum ether / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z - 290 [M + H]⁺ (5) methyl {2-methyl-1 - [(2-trimethylsilanyl-ethoxy) methyl] -1,7-benzoimidazol-5-yl} carboxylate (mixed with methyl {2-methyl-3 - [(2- trimethylsilanyl-ethoxy-methyl] -3H-benzoimidazol-5-yl} -carboxylate)

Mass Spectrum (ESI⁺): m / z = 321 [M + H]⁺

106

Example XXX

- [2- (3-Methanesulfony-1-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) - 8- [3- (tert-butyloxycarbonylamino) - piperidin-1-yl-xanthine

0.22 ml of a 35% hydrogen peroxide solution and 20 mg of sodium tungstate are added to 500 mg of 1- [2- (3-methylsulfanyl-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl -2-buten-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine in 5 ml of methylene chloride. The reaction mixture is stirred overnight at ambient temperature and then 1 ml of methanol is added. After an additional 48 hours, an additional 1.5 ml of 35% hydrogen peroxide solution, a spatula tip of sodium tungsten and two drops of water are added. The next morning, the oxidation is complete by thin layer chromatography, and the reaction mixture is diluted with 50 ml of methylene chloride and washed twice with 30 ml of 10% sodium thiosulfate solution. The organic phase is dried over magnesium sulfate and evaporated to give a viscous resin which is reacted further without further purification.

Yield: 530 mg (100% of theoretical value)

Rf value: 0.72 (silica gel, ethyl acetate)

Mass Spectrum (ESI⁺): m / z = 629 [M + H]⁺

Example XXXI

- [2- (3-carboxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butyloxycarbonylaminol-piperidine-1 -yl] -xanthine

Prepared by the treatment of 1- [2- (3-methoxycarbonyl-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert. butyloxycarbonylamino) -piperidin-1-yl] -xanthine with 3 M sodium hydroxide solution in methanol at ambient temperature.

Rf value: 0.34 (silica gel, methylene chloride / methanol = 9: 1)

Mass Spectrum (ESI⁺): m / z = 595 [M + H]⁺

The following compounds are obtained analogously to Example XXXI:

(1) 1- [2- (2-Carboxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butyloxycarbonyl) lamino) -piperidin-1-yl] -xanthine Rf value: 0.49 (silica gel, methylene chloride / methanol = 9: 1)

107 (2) 1- [2- (2-Carboxymethoxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tertbutyloxy carbonylamino) -piperidin-1-yl] -xanthine (Performed with 4 M potassium hydroxide solution in tetrahydrofuran)

Mass Spectrum (ESI⁺): m / z = 609 [M + H]⁺ (3) 1- [2- (2-Carboxymethylamino-phenyl) -2-oxo-ethyl] -3-methyl-7 - ((E) -2-buten-1-yl) -8 - [(7?) 3- (tert-Butyloxy carbonylamino) -piperidin-1-yl] -xanthine (Performed with 4 M potassium hydroxide solution in tetrahydrofuran)

Rf value: 0.65 (silica gel, cyclohexane / ethyl acetate = 3: 7)

Mass Spectrum (ESI⁺): m / z = 610 [M + H]⁺ (4) 1-Carboxymethyl-3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) piperidin-1-yl] -xanthine

Mass Spectrum (ESI⁺): m / z = 475 [M + H]⁺

Example XXXII 1- {2- [3- (methylaminocarbonyl) phenyl] -2-oxo-ethyl} -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3 (tert) -butyloxycarbonylamino) -piperidin-1-yl] xanthine

A mixture of 190 mg of 1- [2- (3-carboxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-butenl-yl) -8- [3- (tert) -butyloxycarbonylamino) -piperidin-1-yl] -xanthine, 43 μΐ of a 40% aqueous methylamine solution, 103 mg of O- (benzotriazol-1-yl) -N, N, N ', N'-tetramethyluronium tetrafluoroborate, 43 mg N-hydroxybenzotriazole and 45 μΐ triethylamine in 3 ml of tetrahydrofuran are stirred for eight hours at ambient temperature. For working up, the reaction mixture is diluted with ethyl acetate and washed with water, 10% citric acid solution, 10% potassium carbonate solution and saturated sodium chloride solution. The organic phase is evaporated and chromatographed through a silica gel column with methylene chloride / methanol (98: 2 to 80:20) as eluent.

Yield: 173 mg (89% of theoretical value)

Rf value: 0.30 (silica gel, methylene chloride / methanol = 20: 1)

Mass Spectrum (ESI⁺): m / z = 608 [M + H]⁺

108

The following compounds are obtained analogously to Example ΧΧΧΠ:

(1) 1- {2- [3- (Dimethylaminocarbonyl) -phenyl] -2-oxo-ethyl} -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- ( tert-butyloxycarbonylamino) -piperidin-l-yl] -xanthine

Rf value: 0.28 (silica gel, methylene chloride / methanol = 20: 1)

Mass Spectrum (ESI⁺): m / z = 622 [M + H]⁺ (2) 1- {2- [3- (Morpholin-4-yl-carbonyl) -phenyl] -2-oxo-ethyl} -3-methyl-7- (3-methyl-2-buten-1-yl) - 8- [3- (tert-butyloxycarbonylamino) -piperidin-l-yl] -xanthine

Rf value: 0.30 (silica gel, methylene chloride / methanol = 20: 1)

Mass Spectrum (ESI⁺): m / z = 664 [M + H]⁺ (3) 1- {2- [2- (Dimethylaminocarbonyl) -phenyl] -2-oxo-ethyl} -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- ( tert-butyloxycarbonylamino) -piperidin-l-yl] -xanthine

Rf value: 0.30 (silica gel, methylene chloride / methanol = 20: 1)

Mass Spectrum (ESI⁺): m / z = 622 [M + H]⁺ (4) 1- {2- [2- (morpholin-4-yl-carbonyl) -phenyl] -2-oxo-ethyl} -3-methyl-7- (3-methyl-2-buten-1-yl) - 8- [3- (tert-butyloxycarbonylamino) -piperidin-l-yl] -xanthine

Rf value: 0.30 (silica gel, methylene chloride / methanol = 20: 1)

Mass Spectrum (ESI⁺): m / z = 664 [M + H]⁺ (5) 1- (2- {2- [(isopropylaminocarbonyl) methoxy] phenyl} -2-oxo-ethyl) -3-methyl-7- (2-butyn-1 yl) -8- [3- (tert -butyloxycarbonylamino) -piperidin-1-yl] -xanthine (Performed with Hinig base in Ν, Ν-dimethylformamide)

Mass Spectrum (ESI⁺): m / z = 650 [M + H]⁺ (6) 1- (2- {2 - [(Ethylaminocarbonyl) methoxy] phenyl} -2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8 [3- (tert) -butyloxycarbonylamino) -piperidin-1-yl] -xanthine (Performed with a small base in Ν, Ν-dimethylformamide)

Mass Spectrum (ESI⁺): m / z = 636 [M + H]⁺

109 (7) 1- (2- {2- [2-oxo-2- (pyrrolidin-1-yl) -ethoxy] -phenyl} -2-oxo-ethyl) -3-methyl-7- (2-butyne) 1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine (Performed with Hinig base in Ν, Ν-dimethylformamide)

Mass Spectrum (ESI⁺): m / z = 662 [M + H]⁺ (8) 1- (2- {2- [2- (morpholin-4-yl) -2-oxo-ethoxy] -phenyl} -2-oxo-ethyl) -3-methyl-7- (2-butynyl) lyl) -8- [3- (tert-Butyloxycarbonylamino) -piperidin-1-yl] -xanthine (Performed with Hinig base in Ν, Ν-dimethylformamide)

Mass Spectrum (ESI⁺): m / z - 678 [M + H]⁺ (9) 1- (2- {2 - [(methylaminocarbonyl) methylamino] phenyl} -2-oxo-ethyl) -3-methyl-7 - ((E) -2butene-1-yl) - 8- [( 7- (3- (tert-Butyloxycarbonylamino) -piperidin-1-yl] -xanthine Rf value: 0.40 (silica gel, cyclohexane / ethyl acetate / methanol = 5: 4: 1)

Mass Spectrum (ESI⁺): m / z = 623 [M + H]⁺ (10) 1 - [(2-amino-phenylaminocarbonyl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.40 (silica gel, cyclohexane / ethyl acetate / methanol = 5: 4: 1)

Mass Spectrum (ESI⁺): m / z = 565 [M + H]⁺

Example ΧΧΧΠΤ 1-Chloromethyl-4-methyl-isoquinoline hydrochloride

Prepared by treating (4-methyl-isoquinolin-1-yl) -methanol with thionyl chloride in methylene chloride.

Rf value: 0.76 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 95: 5: 0.1) Mass Spectrum (ESI⁺): m / z = 192, 194 [M + H]⁺

The following compounds are obtained analogously to Example ΧΧΧΙΠ:

(1) 1-Chloromethyl-3,4-dimethyl-isoquinoline hydrochloride

Rf value: 0.65 (silica gel, petroleum ether / ethyl acetate = 2: 1)

Mass Spectrum (ESI⁺): m / z = 206, 208 [M + H]⁺

110 (2) 5-chloromethyl-8-methoxy-quinoline hydrochloride

Mass Spectrum (ESI⁺): m / z = 208, 210 [M + H]⁺ (3) 8-chloromethyl-5-methoxy-quinoline hydrochloride

Mass spectrum (E1): m / z = 207, 209 [M]⁺ (4) 2-chloromethyl-3-methylimidazo [1,2-a] pyridine hydrochloride

Rf value: 0.55 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass spectrum (ESI⁺): m / z - 181, 183 [M + H]⁺ (5) 8-chloromethyl-5-methoxy-isoquinoline hydrochloride

Mass Spectrum (ESI⁺): m / z = 208, 210 [M + H]⁺ (6) 1-Chloromethyl-3,4-dimethyl-6,7-dihydro-5 H - [2] pyridine hydrochloride

Rf value: 0.50 (alumina, petroleum ether / ethyl acetate = 10: 1)

Mass Spectrum (ESI⁺): m / z = 196, 198 [M + H]⁺ (7) 1-chloromethyl-3,4-dimethyl-5,6,7,8-tetrahydroisoquinoline hydrochloride

Rf value: 0.50 (alumina, petroleum ether / ethyl acetate = 10: 1)

Mass Spectrum (ESI⁺): m / z = 210, 212 [M + H]⁺ (8) 6-chloromethyl-2,3,8-trimethylquinoxaline hydrochloride

Mass Spectrum (ESI⁺): m / z = 221, 223 [M + H]⁺ (9) 6-chloromethyl-8-methyl-quinoxaline hydrochloride

Mass Spectrum (ESI⁺): m / z = 193.195 [M + H]⁺ (10) 6-chloromethyl-1,2,3,4-tetrahydro-phenanthridine hydrochloride

Rf value: 0.50 (silica gel, petroleum ether / ethyl acetate = 5: 1)

Mass Spectrum (ESI⁺): m / z = 232, 234 [M + H]⁺

111

Example XXXIV 1 - [(4-oxo-3,4-dihydroquinazolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylaminol-piperidine) -1-yl-xanthine

0.5 ml of a 1 M sodium methoxide solution in methanol is added dropwise to a solution of 428 mg of 1-cyanomethyl-3-methyl-7- (2-butyn-1-yl) -8- [3- (tert. butyloxycarbonylamino) piperidin-1-yl] -xanthine in 3 ml of methanol at ambient temperature. After approx. For 20 minutes, the resulting thick suspension is gently heated in a water bath and diluted with 2 ml of methanol. Once the reaction to form the imino ester by thin layer chromatography is complete, the reaction mixture is neutralized with 0.5 ml of 1 M glacial acetic acid solution in methanol and combined with a solution of 130 mg of anthranilic acid in 2 ml of methanol. Gentle heating provides a clear solution that is stirred for 2.5 hours at ambient temperature. Then, the reaction mixture is gently refluxed for approx. 3.5 hours. After standing overnight at ambient temperature, the methanol is distilled off and the residue is stirred with cold water, suction filtered and dried. The crude product is slurried in 5 ml of methanol, gently heated and, after cooling, suction filtered, washed with methanol and dried in desiccator. Yield: 302 mg (56% of theoretical value)

Rf value: 0.55 (silica gel, ethyl acetate)

Mass Spectrum (ESI⁺): m / z = 575 [M + H]⁺

The following compounds are obtained analogously to Example XXXV:

(1) (4-Dichloromethoxy-naphthalen-1-yl) -methanol

Rf value: 0.33 (silica gel, cyclohexane / ethyl acetate = 6: 4)

Mass Spectrum (ESP): m / z = 223 [MH] +

Example XXXV (4-Dimethylamino-naphthalen-1-yl) -methanol

Prepared by reduction of 4-dimethylamino-naphthalene-1-carbaldehyde with sodium borohydride in aqueous tetrahydrofuran.

Rf value: 0.67 (silica gel, cyclohexane / ethyl acetate = 1: 1)

112

Example XXXVI

2-bromo-l- (2,3-dihydro-benzo | T.41dioxin-5-yl) -ethanone

Prepared by bromination of 1- (2,3-dihydro-benzo [1,4] dioxin-5-yl) -ethanone in methylene chloride under gentle cooling in an ice bath. The dibromo compound formed as a by-product is separated from by column chromatography.

Mass Spectrum (ESI⁺): m / z = 257, 259 [M + H]⁺

Rf value: 0.92 (silica gel, methylene chloride)

The following compounds are obtained analogously to Example XXXVI:

(1) 7- (2-Bromo-acetyl) -3-methyl-3/7-benzooksazol-2-one (bromination is carried out in dioxane at 40 ° C; the product is contaminated with about 20% dibromo compound)

Rf value: 0.44 (silica gel, petroleum ether / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z = 270, 272 [M + H]⁺ (2) 1-Benzo [1,3] dioxol-4-yl-2-bromo-ethanone

Mass Spectrum (ESI⁺): m / z = 243, 245 [M + H]⁺

Rf value: 0.94 (silica gel, methylene chloride) (3) 2- [2- (2-bromo-acetyl) -phenoxy] -N-ethyl-acetamide (bromination is carried out with copper (II) bromide in dioxane)

Mass Spectrum (ESI⁺): m / z = 300, 302 [M + H]⁺ (4) 4- (2-bromoacetyl) -3-methyl-3/7-benzooksazol-2-one

Rf value: 0.67 (silica gel, methylene chloride / methanol = 99: 1)

Mass Spectrum (ESI⁺): m / z = 270, 272 [M + H]⁺ (5) 2- [2- (2-Bromo-acetyl) -phenoxy] -7V-methyl-acetamide

Mass Spectrum (ESI⁺): m / z = 386, 388 [M + H]⁺ (6) 7- (2-Bromoacetyl) -3 - [(2-trimethylsilanyl-ethoxy) methyl] -3H-benzoxazol-2-one Rf value: 0.84 (silica gel, methylene chloride / methanol = 99 : 1)

113

Mass Spectrum (ESI⁺): m / z = 384, 386 [M + H]⁺ (7) 4- (2-Bromoacetyl) -1,3-dimethyl-1,3-dihydro-benzoimidazol-2-one

Rf value: 0.38 (silica gel, ethyl acetate / petroleum ether = 1: 1)

Mass Spectrum (ESI⁺): m / z = 283, 285 [M + H]⁺ (8) 4- (2-Bromo-acetyl) -3 - [(2-trimethylsilanyl-ethoxy) methyl] -37β-benzooksazol-2-one Rf value: 0.82 (silica gel, methylene chloride / methanol = 99: 1) (9) 4- (2-bromoacetyl) -1-ethoxycarbonyl-3-methyl-1,3-dihydro-benzoimidazol-2-one Rf value: 0.39 (silica gel, petroleum ether / ethyl acetate = 2: 1)

Mass Spectrum (ESI⁺): m / z = 341, 343 [M + H]⁺ (10) 2-Bromo-1- (2,2-difluoro-benzo [1,3] dioxol-4-yl) -ethanone

Mass Spectrum (ESI): m / z = 277, 279 [MH] +

Example XXXVII (2,3-Dihydro-benzoyl 1,41-dioxin-5-yl) -ethanone

Prepared by reacting 1- (2,3-dihydroxy-phenyl) -ethanone with 1,2-dibromethane in the presence of potassium carbonate in Ν, Ν-dimethylformamide at 100 ° C.

Rf value: 0.43 (silica gel, ethyl acetate / petroleum ether = 1: 4)

Mass Spectrum (ESI⁺): m / z = 179 [M + H]⁺

Example XXXVIII

- [(3-methyl-4-oxo-3,4-dihydroquinazolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylaminol) piperidin-1-yl-xanthine

Prepared by reaction of 1 - [(4-oxo-3,4-dihydroquinazolin-2-yl) methyl] -3-methyl-7- (2butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) ) -piperidin-1-yl] -xanthine with methyl iodide in the presence of potassium carbonate in Ν, Ν-dimethylformamide at ambient temperature.

Rf value: 0.50 (silica gel, ethyl acetate)

Mass Spectrum (ESI⁺): m / z = 589 [M + H]⁺

114

The following compounds are obtained analogously to Example XXXVIII:

(1) 7-Acetyl-3-methyl-3Z / -benzooksazol-2-one (The methylation is carried out in the presence of sodium carbonate in methanol)

Rf value: 0.46 (silica gel, petroleum ether / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z = 192 [M + H]⁺ (2) 4-Acetyl-3-methyl-3H-benzooksazol-2-one (The methylation is carried out in the presence of sodium carbonate in methanol under reflux)

Rf value: 0.67 (silica gel, methylene chloride / methanol = 99: 1)

Mass Spectrum (ESI⁺): m / z = 192 [M + H]⁺ (3) 4-Acetyl-1,3-dimethyl-1,3-dihydro-benzoimidazol-2-one (Performed in the presence of potassium tert-butoxide)

Rf value: 0.40 (silica gel, ethyl acetate / petroleum ether = 2: 1)

Mass Spectrum (ESI⁺): m / z = 205 [M + H]⁺ (4) 4-Acetyl-1-ethoxycarbonyl-3-methyl-1,3-dihydro-benzoimidazol-2-one

Rf value: 0.23 (silica gel, petroleum ether / ethyl acetate = 2: 1)

Mass Spectrum (ESI⁺): m / z = 263 [M + H]⁺ (5) 1 - [(1-methyl-17β-benzoimidazol-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [3- (tert-butyloxycarbonylamino) -piperidine -1-yl] -xanthine Mass Spectrum (ESI⁺): m / z = 561 [M + H]⁺ (6) 1- {[1- (2-Cyanoethyl) -1H-benzoimidazol-2-yl] methyl} -3-methyl-7- (2-butyn-1-yl) -8- [3 (tert) -butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Rf value: 0.50 (silica gel, cyclohexane / ethyl acetate / methanol = 5: 4: 1)

Mass Spectrum (ESI⁺): m / z = 600 [M + H]⁺ (7) 1- ({1 - [(methylaminocarbonyl) methyl] -1H-benzoimidazol-2-yl} methyl) -3-methyl-7- (2butyn-1-yl) - 8- [3- (tertiary) butyloxycarbonylamino) -piperidin-1-yl] -xanthine

115

Rf value: 0.45 (silica gel, cyclohexane / ethyl acetate / methanol = 5: 4: 1)

Mass Spectrum (ESI⁺): m / z = 618 [M + H]⁺ (8) 1 - [(1-Benzyl-1H-benzoimidazol-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidine 1-yl] -xanthine

Rf value: 0.50 (silica gel, cyclohexane / ethyl acetate / methanol = 5: 4: 1)

Mass Spectrum (ESI⁺): m / z = 637 [M + H]⁺

Example XXXIX 1- [2- (2-cyanomethylamino-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Prepared by reaction of 1- [2- (2-amino-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-butenl-yl) -8- [3- (tert-butyl) butyloxycarbonylamino) -piperidin-1-yl] -xanthine with paraformaldehyde and potassium cyanide in the presence of zinc chloride in glacial acetic acid at 40 ° C.

Rf value: 0.45 (silica gel, cyclohexane / ethyl acetate = 3: 7)

Mass Spectrum (ESI⁺): m / z = 605 [M + H]⁺

Example XL

- [2- (2-amino-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(5) - 3- (tert-butyloxycarbonylamino) -piperidine 1-yl] -xanthine prepared by reduction of 1- [2- (2-nitrophenyl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 [(5 ) - 3- (tert-Butyloxycarbonylamino) -piperidin-1-yl] -xanthine with sodium dithionite in a mixture of methyl glycol and water (2: 1) at 100 ° C.

Rf value: 0.34 (silica gel, methylene chloride / methanol = 95: 5)

The following compounds are obtained analogously to Example XL:

(1) 1- [2- (2-Amino-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(7?) - 3- ( tert-Butyloxycarbonylamino) -piperidin-1-yl] -xanthine Rf value: 0.50 (silica gel, cyclohexane / ethyl acetate = 4: 6)

116

Example XLI

2-Chloromethyl-4-methyl-quinazoline

Prepared by treating 2.95 g of 2-chloromethyl-4-methyl-quinazoline-3-oxide with 6 ml of phosphorus trichloride in 150 ml of chloroform under reflux.

Yield: 1.75 g (57% of theoretical value)

Rf value: 0.81 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 193, 195 [M + H]⁺

Example XLII

2-chloromethyl-4-dimethylamino-quinazoline

A freshly prepared solution of 202 mg of dimethylamine in 3.2 ml of tetrahydrofuran is added dropwise to 500 mg of 4-chloro-2-chloromethyl-quinazoline in 5 ml of tetrahydrofuran under cooling with an ice bath. Then, the reaction mixture is stirred for an additional 3.5 hours under cooling with an ice bath and then for an additional 30 minutes at ambient temperature.

The solvent is then gently distilled off using a rotary evaporator and the residue is taken up in methylene chloride. The solution is washed with saturated sodium bicarbonate solution and water, dried over magnesium sulfate and evaporated. The solid residue is stirred with a little tert-butyl methyl ether, suction filtered, washed with petroleum ether and dried under vacuum.

Yield: 323 mg (62% of theoretical value)

Rf value: 0.60 (silica gel, cyclohexane / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z = 222, 224 [M + H]⁺

The following compounds are obtained analogously to Example XLII:

(1) 2-Chloromethyl-4- (morpholin-4-yl) quinazoline

Rf value: 0.50 (silica gel, cyclohexane / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z = 264, 266 [M + H]⁺ (2) 2-chloromethyl-4- (piperidin-1-yl) quinazoline

Rf value: 0.70 (silica gel, cyclohexane / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z = 262, 264 [M + H]⁺

117 (3) 4- [4- (tert-Butyloxycarbonyl) -piperazin-1-yl] -2-chloromethyl-quinazoline

Rf value: 0.57 (silica gel, cyclohexane / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z = 363, 365 [M + H]⁺ (4) 2-chloromethyl-4- (pyrrolidin-1-yl) quinazoline

Rf value: 0.50 (silica gel, cyclohexane / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z = 248, 250 [M + H]⁺ (5) 2-Chloromethyl-4-ethoxyquinazoline (The reaction is carried out with sodium ethoxide in ethanol at ambient temperature.)

Rf value: 0.50 (silica gel, cyclohexane / ethyl acetate = 3: 1)

Mass Spectrum (ESI⁺): m / z = 223, 225 [M + H]⁺ (6) 2-Chloromethyl-4-isopropyloxyquinazoline (The reaction is carried out with sodium isopropoxide in isopropanol at ambient temperature.)

Rf value: 0.70 (silica gel, cyclohexane / ethyl acetate = 3: 1)

Mass Spectrum (ESI⁺): m / z = 237, 239 [M + H]⁺ (7) 2-Chloromethyl-4-phenyloxy-quinazoline (The reaction is carried out with sodium hydride and phenol in tetrahydrofuran at ambient temperature.)

Rf value: 0.65 (silica gel, cyclohexane / ethyl acetate = 3: 1)

Mass Spectrum (ESI⁺): m / z = 271, 273 [M + H]⁺

Example XLin

- (2- {2 - [(ethoxycarbonyl) methylamino] -phenyl} -2-oxo-ethyl) -3-methyl-7 - ((E) -2-buten-1-yl) 8- [3- (tert -butyloxycarbonylaminoj-piperidin-1-yl] -xanthine

A solution of 110 μΐ of ethyl diazoacetate in 0.5 ml of toluene is added dropwise to 531 mg of 1- [2- (2 amino-phenyl) -2-oxo-ethyl] -3-methyl-7 - ((E) -2-butene -1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine and 10 mg of methyl trioxorhenium in 4.5 ml of toluene at ambient temperature under an argon atmosphere. The reaction mixture is stirred for 15 hours at ambient temperature. Then approx. 5 mg methyl trioxorhenium and 20 μΐ

118 ethyl diazoacetate is added, and the reaction mixture is heated to 50 ° C for two hours. After cooling to ambient temperature, an additional 5 mg of methyl trioxorhenium and 20 μΐ of ethyl diazoacetate are added. After a further 16 hours at ambient temperature, the reaction mixture is combined with 5 ml of conc. aqueous ammonia, shaken thoroughly and added to an Extrelut column. After 15 minutes, it is rinsed with 200 ml of methylene chloride. The methylene chloride solution is evaporated and chromatographed through a silica gel column with cyclohexane / ethyl acetate / isopropanol (8: 2: 0 to 8: 1: 1) as eluent.

Yield: 220 mg (36% of theoretical value)

Rf value: 0.40 (silica gel, cyclohexane / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z - 638 [M + H]⁺

Example XLIV 1 - [(2-cyano-benzofuran-3-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylaminol-piperidin-1-yl) xanthine

A mixture of 215 mg of 1- {2- [2-cyanomethoxy-phenyl] -2-oxo-ethyl} -3-methyl-7- (2-butynyl) -8- [3- (tert-butyloxycarbonylamino) - piperidin-1-yl] -xanthine and 244 mg of cesium carbonate in 4 ml of Ν, Ν-dimethylformamide are stirred for two hours at 50 ° C and then for another three hours at 70 ° C. For working up, the reaction mixture is combined with water and the precipitate formed is suction filtered and dried.

Yield: 130 mg (62% of theoretical value)

Mass Spectrum (ESI⁺): m / z = 572 [M + H]⁺

Example XLV 1- [2- (3-methyl-2-oxo-2,3-dihydro-1 H -benzoimidazol-4-yl) -2-oxo-ethyl] -3-methyl-7- (2butyl-1 -yl) - 8-13 - (tert-Butyloxycarbonylamino) -piperidin-1-yl-xanthine

Prepared by Treatment of 1- [2- (1-Ethoxycarbonyl-3-methyl-2-oxo-2,3-dihydro-17-benzoimidazol-4-yl) -2-oxo-ethyl] -3-methyl-7- (2 -butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine with 1N sodium hydroxide solution in methanol at ambient temperature.

Rf value: 0.36 (silica gel, ethyl acetate)

Mass Spectrum (ESI⁺): m / z = 605 [M + H]⁺

119

Example XLVI

4-Acetyl-l-ethoxycarbonyl-1,3-dihydro-benzoimidazol-2-one

5.29 g of diethyl dicarbonate and 611 mg of dimethylaminopyridine are added to 1.50 g of 1- (2,3-diaminophenyl) -ethanone in 75 ml of methylene chloride. The reaction mixture is stirred for three hours at ambient temperature, then an additional 100 mg of dimethylaminopyridine and 1 ml of diethyl dicarbonate are added and the mixture is stirred for an additional 20 hours at ambient temperature. For working up, the reaction mixture is diluted with methylene chloride, washed with 2N citric acid solution, as well as saturated sodium hydrogen carbonate solution and saturated sodium chloride solution, dried over magnesium sulfate and evaporated. The residue is chromatographed through a silica gel column with petroleum ether / ethyl acetate (3: 1 to 1: 2) as the eluent. The desired product is stirred with a little tert-butyl methyl ether, suction filtered, washed with a little ethyl acetate and tert-butyl methyl ether and dried.

Yield: 900 mg (36% of theoretical value)

Rf value: 0.15 (silica gel, petroleum ether / ethyl acetate = 2: 1)

Mass Spectrum (ESI⁺): m / z = 249 [M + H]⁺

Example XLVII 1 - [(4-Amino-quinazolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino] -piperidin-1-yl xanthine

501 mg of 1-cyanomethyl-3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) piperidin-1-yl] -xanthine is added to a mixture of 17 mg of potassium tert -butoxide in 10 ml of methanol. After brief heating with stirring, a clear solution is formed, and after approx. For about 20 minutes, the nitrile is substantially converted to the imino ester by thin layer chromatography. 206 mg of 2-amino-benzamidine hydrochloride is then added and the reaction mixture is refluxed for four hours. After cooling to ambient temperature, the formed precipitate is suction filtered, washed with methanol and dried.

Yield: 143 mg (23% of theoretical value)

Rf value: 0.15 (silica gel, ethyl acetate)

Mass Spectrum (ESI⁺): m / z = 574 [M + H]⁺

120

Example XLVIII 1- (2-Phenyl-2-oxo-ethyl) -3-methyl-7 - ((Z) -2-buten-1-yl) -8- [3- (tert-butyloxycarbonylamino) piperidine-1- yl-xanthine

150 mg of 1- (2-phenyl-2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine is hydrogenated in a mixture of 5 ml of tetrahydrofuran and 5 ml of methanol in the presence of 30 mg of 5% m palladium on activated charcoal (contaminated with quinoline) at ambient temperature until the calculated amount of hydrogen is taken up. Then, a spatula tip activated charcoal is added and the mixture is suction filtered. The filtrate is evaporated and the crude product is purified by chromatography through a silica gel column with cyclohexane / ethyl acetate (7: 3 to 4: 6).

Yield: 120 mg (85% of theoretical value)

Rf value: 0.40 (silica gel, cyclohexane / ethyl acetate = 4: 6)

Mass Spectrum (ESI⁺): m / z = 537 [M + H]⁺

Example XLIX

8-hydroxymethyl-5-methoxy-quinoline

148 Sodium hydride (about 60% in mineral oil) is added portionwise to a solution of 640 mg of 8-hydroxymethylquinolin-5-ol in Ν, Ν-dimethylformamide under cooling with an ice bath, and the reaction mixture is slowly warmed to ambient temperature. After the evolution of gas has ceased, 230 μΐ of methyl iodide is added dropwise while cooling with an ice bath and then the reaction mixture is stirred for approx. two hours at ambient temperature. For working up, it is poured into ice water, saturated with sodium chloride and extracted with a mixture of diethyl ether and ethyl acetate. The combined extracts are washed with saturated sodium chloride solution, dried over magnesium sulfate and evaporated. The flask residue is extracted with petroleum ether and the supernatant is decanted. The crude product is purified through a silica gel column with ethyl acetate as the eluent.

Yield: 470 mg (68% of theoretical value)

Rf value: 0.70 (silica gel, ethyl acetate)

Mass Spectrum (ESI⁺): m / z = 190 [M + H]⁺

121

The following compounds are obtained analogously to Example XLIX:

(1) 8-hydroxymethyl-5-methoxy-isoquinoline

Rf value: 0.40 (silica gel, methylene chloride / methanol = 10: 1)

Mass Spectrum (ESI⁺): m / z = 190 [M + H]⁺

Example L

8-hydroxymethyl-quinolin-5-ol

3.40 g of quinolin-5-ol are combined with 8 ml of conc. hydrochloric acid and 8 ml of 37% formalin solution under cooling with an ice bath. Then, hydrogen chloride gas is passed through the reaction mixture for about two hours, while the temperature is slowly increased. The reaction mixture is stirred first overnight under cooling with an ice bath, then at ambient temperature and then evaporated under vacuum. The flask residue is taken up in water, covered with a layer of diethyl ether and adjusted to pH 10 with dilute ammonia solution under cooling with an ice bath and with vigorous stirring. After a further two hours of vigorous stirring at ambient temperature, the organic phase is separated and the aqueous phase is extracted with diethyl ether. The combined organic phases are washed with water and saturated sodium chloride solution, dried over magnesium sulfate and evaporated. The flask residue is chromatographed through a silica gel column with methylene chloride / methanol (20: 1) as the eluent.

Yield: 660 mg (16% of theoretical value)

Mass Spectrum (ESI⁺): m / z = 176 [M + H]⁺

The following compounds are obtained analogously to Example L:

(1) 8-hydroxymethyl-isoquinolin-5-ol

Rf value: 0.50 (silica gel, methylene chloride / methanol = 5: 1)

Mass Spectrum (ESI⁺): m / z = 176 [M + H]⁺

Example LI 1 - [(2-cyclopropyl-quinazolin-4-yl) methyl] -3-methyl-7 - [(1-cyclopenten-1-yl) methyl] -8- [3- (tert-butyloxycarbonylamino) -piperidine-1 -yll-xanthine

122

A mixture of 250 mg of 1- (2- {2 - [(cyclopropylcarbonyl) amino] phenyl} -2-oxoethyl) -3methyl-7- [(1-cyclopenten-1-yl) methyl] -8- [ 3- (tert-Butyloxycarbonylamino) -piperidin-1-yl] xanthine and 7.5 ml of ethanolic ammonia solution (6 M) are heated to 150 ° C for seven hours in a pressure flask. For work up, the reaction mixture is evaporated and chromatographed through a silica gel column with methylene chloride / methanol (100: 0 to 70:30) as eluent. The contaminated product fraction is evaporated and again purified through a reverse phase HPLC column with water / acetonitrile / trifluoroacetic acid (65: 15: 0.08 to 0: 100: 0.1) as eluent. The product fractions are evaporated, made alkaline with dilute sodium hydroxide solution and extracted with methylene chloride. The combined extracts are dried over magnesium sulfate and evaporated.

Yield: 40 mg (14% of theoretical value)

Rf value: 0.40 (silica gel, methylene chloride / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z = 627 [M + H]⁺

Example Lit.

4- (2-bromo-acetyl) -l, 3-bis - [(2-trimethylsilanyl-ethoxy) methyl] -l, 3-dihydrobenzoimidazol-2-one

520 2 mg of 2-pyrrolidinone hydrotribromide and 89 mg of 2-pyrrolidinone are added to 420 mg of 4acetyl-1,3-bis - [(2-trimethylsilanyl-ethoxy) methyl] -1,3-dihydro-benzoimidazol-2-one in 5 ml tetrahydrofuran under argon atmosphere. The reaction mixture is refluxed for two hours and then suction filtered while still warm. The filter cake is washed with tetrahydrofuran and the filtrate is evaporated to give 660 mg of a tan solid. This is stirred with a little methanol, suction filtered, washed with a little methanol and dried. The crude product is resold without further purification.

Yield: 430 mg (87% of theoretical value)

Rf value: 0.23 (silica gel, petroleum ether / ethyl acetate = 9: 1)

Mass Spectrum (EI): m / z = 514, 516 [M]⁺

The following compounds are obtained analogously to Example LE:

(1) 7- (2-Bromoacetyl) -1- (tert-butyloxycarbonyl) -1,7-indole

Rf value: 0.33 (silica gel, petroleum ether / ethyl acetate = 9: 1)

Mass Spectrum (ESI⁺): m / z = 338, 340 [M + H]⁺

123 (2) 2-Bromo-1- (3-isopropyloxy-phenyl) -ethanone (Made with phenyltrimethylammonium tribromide in methylene chloride)

Rf value: 0.39 (silica gel, cyclohexane / ethyl acetate = 9: 1) (3) 2-bromo-1- (3-difluoromethoxy-phenyl) -ethanone (Made with phenyltrimethylammonium tribromide in methylene chloride)

Rf value: 0.24 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 1)

Example ΕΠΙ

Methyl 3-methyl-imidazole 1,2-alpyridine-2-carboxylate

A mixture of 1.91 g of 2-aminopyridine and 4.40 g of methyl 3-bromo-2-oxo-butyrate in 40 ml of ethanol is refluxed for 6 hours and then allowed to stand for 2 days at ambient temperature. The solvent is distilled off using a rotary evaporator and the crude product is purified by chromatography through a silica gel column with methylene chloride / methanol / methanolic ammonia solution (95: 4: 1 to 90: 9: 1) as eluent. 560 mg of the ethyl ester is isolated as a by-product.

Yield: 2.09 g (54% of theoretical value)

Rf value: 0.20 (silica gel, methylene chloride / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z = 191 [M + H]⁺

Example LIV

2-chloromethyl-4-isopropylquinazolin

Dry hydrogen chloride gas is passed under stirring and at ambient temperature through a solution of 2.86 g of 1- (2-amino-phenyl) -2-methyl-propan-1-one and 1.33 ml of chloroacetonitrile in 14 ml of dioxane in ca. . five hours. Subsequently, the dioxane is substantially distilled off under water jet vacuum. The honey-like residue is combined with ice water and the resulting suspension is made alkaline with saturated potassium carbonate solution under cooling with an ice bath. The precipitate is suction filtered, washed with water and dried.

124

The crude product is purified by chromatography through a silica gel column with petroleum ether / methylene chloride (8: 2 to 0: 1) as eluent.

Yield: 1.80 g (58% of theoretical value)

Rf value: 0.30 (silica gel, methylene chloride / petroleum ether = 1: 1)

Mass Spectrum (ESI⁺): m / z = 221, 223 [M + H]⁺

Example LV

-chloromethyl-3-trifluoromethyl-3,4-dihydroisoquinoline

530 mg2V- (1-benzyl-2,2,2-trifluoro-ethyl) -2-chloro-acetamide (prepared by reaction of 1benzyl-2,2,2-trifluoro-ethylamine with chloroacetyl chloride in the presence of triethylamine) and 0.74 Phosphorus oxychloride is added to 4.00 g of polyphosphoric acid. The viscous mixture is stirred for 1.5 hours at 130 ° C. For work up, the reaction mixture is cooled and combined with ice water, stirred vigorously for ten minutes and suction filtered. The filter cake is dissolved in ethyl acetate and the solution is dried over magnesium sulfate and evaporated to give a white solid. Yield: 415 mg (84% of theoretical value)

Rf value: 0.55 (alumina, petroleum ether / ethyl acetate = 10: 1)

Mass Spectrum (ESI⁺): m / z = 248, 250 [M + H]⁺

The following compound is obtained analogously to Example LV:

(1) 1-Methyl-3-trifluoromethyl -3,4-dihydro-isoquinoline (The starting material 2- (1-benzyl-2,2,2-trifluoro-ethyl) -acetamide is obtained by reaction of 1-benzyl-2.2 2-trifluoroethylamine with acetic anhydride.)

Example LVI

3-bromomethyl-1- (1-cyano-1-methyl-ethyl) -isoquinoline

A mixture of 375 mg of 1- (1-cyano-1-methyl-ethyl) -3-methyl-isoquinoline and 321 mg of N-bromosuccinimide in 5 ml of carbon tetrachloride is combined with a spatula of 2,2azoisobutyric acid dinitrile and refluxed for about six hours. The cooled reaction mixture is filtered and evaporated. The flask residue is resold without further purification.

Rf value: 0.70 (silica gel, cyclohexane / ethyl acetate = 3: 1)

125

The following compounds are obtained analogously to Example LVI:

(1) 6 ~ bromomethyl-1 - [(2-trimethylsilanyl-ethoxy) methyl] -1H-quinolin-2-one (2) 1 ~ bromomethyl-4-bromo-3-methoxy-isoquinoline (3) 2 ~ bromomethyl- [1,5] naphthyl ridin

Mass Spectrum (ESI +): m / z - 223, 225 [M + H] + (4) 5-Bromomethyl- [1,6] naphthyridine

Rf value: 0.48 (silica gel, ethyl acetate / methanol = 98: 2) (5) 7-bromomethyl-5-phenylquinoxaline

Rf value: 0.85 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 299, 301 [M + H]⁺ (6) 4-bromomethyl- [1,5] naphthyridine

Rf value: 0.56 (silica gel, methylene chloride / ethyl acetate = 7: 3)

Mass Spectrum (ESI⁺): m / z = 223, 225 [M + H]⁺ (7) 1-Bromomethyl-3-trifluoromethyl-isoquinoline

Mass Spectrum (ESI⁺): m / z = 290, 292 [M + H]⁺ (8) 1-Bromomethyl-3-difluoromethyl-isoquinoline

Mass Spectrum (ESI⁺): m / z = 272, 274 [M + H]⁺ (9) 1- Bromomethyl-4-chloro-3-methoxy-isoquinoline

Example LVT1

- (1-cyano-1-methyl-ethyl) -3-methyl-isoquinoline

3.30 g of 2,2-azoisobutyric acid dinitrile is added to 1.60 g of 3-methyl-isoquinoline-N-oxide in 30 ml of toluene. The reaction mixture is stirred for six hours at 85 ° C and then allowed to stand for two days

126 at ambient temperature. For working up, the reaction mixture is extracted with 20% hydrochloric acid. The combined aqueous phases are diluted with methylene chloride, made alkaline with saturated potassium carbonate solution under cooling with an ice bath, and extracted with methylene chloride. The combined methylene chloride extracts are dried over magnesium sulfate and evaporated. The residue is chromatographed through a silica gel column with cyclohexane as the eluent.

Yield: 375 mg (18% of theoretical value)

Mass Spectrum (ESI⁺): m / z = 211 [M + H]⁺

Rf value: 0.75 (silica gel, cyclohexane / ethyl acetate = 3: 1)

Example LVHI 1- (2-cyanoimino-2-phenyl-ethyl) -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidin-1-yl-xanthine (E / Z mixture)

0.48 ml of a 1M solution of titanium tetrachloride in methylene chloride is added dropwise to 244 mg of 1- (2-phenyl-2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8 - [3- (tert-butyloxycarbonylamino) piperidin-1-yl] -xanthine in 7 ml of methylene chloride. Then 88 μΐ of 1,3-bis (trimethylsilyl) carbodiimide is added and the mixture is stirred for four hours at ambient temperature. For working up, the reaction mixture is diluted with methylene chloride and poured into ice water. The organic phase is washed with 0.5 N citric acid, dried over magnesium sulfate and evaporated. The crude product is purified by chromatography through a silica gel column with methylene chloride / methanol (98: 2 to 95: 5) as eluent.

Yield: 206 mg (97% of theoretical value)

Mass Spectrum (ESI '): m / z = 557 [MH]

Rf value: 0.16 (silica gel, cyclohexane / ethyl acetate = 1: 1)

Example LIX 1 - [(1H-benzoimidazol-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino] piperidin-1-yl] - xanthine

350 mg 1 - [(2-amino-phenylaminocarbonyl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine is refluxed 3 ml glacial acetic acid for two hours. Then, the reaction mixture is evaporated and the flask residue is combined with 5 ml of 1 M sodium hydroxide solution and washed with methylene chloride. Then, the aqueous phase is acidified with 1 M hydrochloric acid and extracted with methylene chloride. The total extracts

127 is evaporated and chromatographed through a silica gel column with cyclohexane / ethyl acetate / methanol (6: 4: 0 to 5: 4: 1) as eluent.

Yield: 250 mg (74% of theoretical value)

Mass Spectrum (ESI⁺): m / z = 547 [M + H]⁺

Example LX

Ethyl 3,4-dimethyl-6,7-dihydro-5β- [21pyrindine-1-carboxylate

Prepared by treating 1.16 g of ethyl 3,4-dimethyl-4a- (pyrrolidin-1-yl) -5,6,7,7atetrahydro-4a // - [2] pyrindin-1-carboxylate with 1.08 70 g of 3-chloro-perbenzoic acid in 50 ml of methylene chloride at ambient temperature.

Yield: 850 mg (97% of theoretical value)

Rf value: 0.30 (alumina, petroleum ether / ethyl acetate = 5: 1)

Mass Spectrum (ESI⁺): m / z = 220 [M + H]⁺

The following compounds are obtained analogously to Example LX:

(1) Ethyl 3,4-dimethyl-5,6,7,8-tetrahydroisoquinoline-1-carboxylate

Rf value: 0.35 (alumina, petroleum ether / ethyl acetate = 5: 1)

Mass Spectrum (ESI⁺): m / z = 234 [M + H]⁺

Example LXI

Ethyl 3,4-dimethyl-4a (pyrrolidin-1-yl) -5,6,7,7a-tetrahydro-4a // - in 21 pyrindin-1-carboxylate

Prepared by reacting 2.50 g of ethyl 5,6-dimethyl [1,2,4] triazine-3-carboxylate with 2.74 g of 1- (cyclopenten-1-yl) pyrrolidine in 25 ml of chloroform at ambient temperature .

Yield: 3.00 g (75% of theoretical value)

Rf value: 0.60 (alumina, petroleum ether / ethyl acetate = 5: 1)

Mass Spectrum (ESI⁺): m / z = 291 [M + H]⁺

The following compounds are obtained analogously to Example LXI:

(1) Ethyl 3,4-dimethyl-4a- (pyrrolidin-1-yl) -4a, 5,6,7,8,8a-hexahydro-isoquinoline-carboxylate

128

Rf value: 0.60 (alumina, petroleum ether / ethyl acetate = 5: 1) Mass spectrum (ESI⁺): m / z = 305 [M + H]⁺

129

Example LXII

Methyl 2,3,8-trimethyl-quinoxaline-6-carboxylate

Prepared by reaction of 1.60 g of methyl 3,4-diamino-5-methyl-benzoate with 0.86 ml of diacetyl in a mixture of water and ethanol under reflux.

Yield: 1.53 g (80% of theoretical value)

Rf value: 0.63 (silica gel, cyclohexane / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z = 231 [M + H]⁺

The following compounds are obtained analogously to Example LXII:

(1) methyl 8-methyl-quinoxaline-6-carboxylate (reaction is carried out with glyoxal in water.)

Rf value: 0.55 (silica gel, cyclohexane / ethyl acetate = 1: 1)

Mass Spectrum (ESI⁺): m / z = 203 [M + H]⁺ (2) 5-Bromo-7-methyl-quinoxaline (the reaction is carried out with glyoxal in a water / ethanol mixture.)

Rf value: 0.75 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 223, 225 [M + H]⁺

Example LXIII

Methyl 3,4-diamino-5-methyl-benzoate

Prepared by reduction of methyl 3-nitro-4-amino-5-methyl-benzoate at a hydrogen partial pressure of 50 psi, in the presence of Raney nickel in methanol at ambient temperature. Rf value: 0.40 (silica gel, tert-butyl methyl ether)

Example LXIV

Methyl 3-nitro-4-amino-5-methyl-benzoate

Prepared by treating 3-nitro-4-acetylamino-5-methyl-benzoic acid with hydrogen chloride gas in methanol at ambient temperature and then heating under reflux.

Mass Spectrum (ESI⁺): m / z = 211 [M + H]⁺

Rf value: 0.75 (silica gel, tert-butyl methyl ether / acetic acid = 99: 1)

130

Example LXV

- (2-Phenyl-2-oxo-ethyl) -3-methyl-7 - ((E) -1-buten-1-yl) -8-bromo-xanthine

0.13 ml of 35% hydrogen peroxide solution is added to 290 mg of 1- (2-phenyl-2-oxoethyl) -3methyl-7- (1-phenylsulfanyl-butyl) -8-bromo-xanthine in 6 ml of hexafluoroisopropanol. The reaction mixture is stirred for one hour at ambient temperature, diluted with methylene chloride and washed with sodium thiosulfate solution. The organic phase is dried over magnesium sulfate and evaporated. The flask residue is taken up in 6 ml of toluene and refluxed for eight hours. Then the toluene is distilled off under vacuum and the crude product is purified through a silica gel column with methylene chloride / methanol (100: 0 to 95: 5) as the eluent.

Yield: 104 mg (45% of theoretical value)

Rf value: 0.61 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 417, 419 [M + H]⁺

The following compounds are obtained analogously to Example LXV:

(1) 3-methyl-7- (3-methyl-1-butene-1-yl) - 8-bromo-xanthine

Rf value: 0.24 (silica gel, methylene chloride / methanol = 95: 5)

Mass Spectrum (ESI⁺): m / z = 313, 315 [M + H]⁺

Example LXVI 1-methanesulfonylloxymethyl-4-difluoromethoxyn-naphthalene

Increase by reaction of (4-difluoromethoxy-naphthalen-1-yl) -methanol with methanesulfonic acid chloride in methylene chloride in the presence of triethylamine.

The following compounds are obtained analogously to Example LXVI:

(1) (E) -1-Methanesulfonyloxy-3- (2-nitrophenyl) -2-propene (2) (E) -1-Methanesulfonyloxy-3-pentafluorophenyl-2-propene (3) (E) -1 -methanesulfonyloxy-3- (2-trifluoromethyl-phenyl) -2-propene

131 (4) (E) -1-methanesulfonyloxy-3- (3-trifluoromethyl-phenyl) -2-propene (5) (E) -1-methanesulfonyloxy-3- (4-trifluoromethyl-phenyl) -2-propene

Example LXVII

7-methyl-5-phenylquinoxaline

A mixture of 400 mg of 5-bromo-7-methyl-quinoxaline, 244 mg of phenylboronic acid and 100 mg of tetrakis (triphenylphosphine) palladium in 12 ml of dioxane, 4 ml of methanol and 3.6 ml of 1 M aqueous sodium carbonate solution is refluxed in wood. hours under argon atmosphere. Then, the reaction mixture is evaporated and the residue is partitioned between ethyl acetate and water. The ethyl acetate phase is separated, dried over magnesium sulfate and evaporated. The crude product is purified by chromatography through a silica gel column with cyclohexane / ethyl acetate (85:15 to 70:30) as eluent.

Yield: 390 mg (66% of theoretical value)

Rf value: 0.36 (silica gel, petroleum ether / ethyl acetate = 5: 1)

Mass Spectrum (ESI⁺): m / z - 221 [M + H]⁺

Example LXVIII

methyl-3-trifluoromethyl-isoquinoline

Prepared by treating 905 mg of 1-chloromethyl-3-trifluoromethyl-3,4-dihydroisoquinoline with 420 mg of potassium tert-butoxide in 10 ml of tetrahydrofuran at ambient temperature. Yield: 755 mg (98% of theoretical value)

Mass Spectrum (ESI⁺): m / z = 212 [M + H]⁺

The following compounds are obtained analogously to Example LXVIII:

(1) 1-Methyl-3-difluoromethyl-isoquinoline (Prepared from 1-methyl-3-trifluoromethyl-3,4-dihydro-isoquinoline)

Mass Spectrum (ESI⁺): m / z = 194 [M + H]⁺

132

Example LXIX

4-chloro-3-methoxy-1-methyl-isoquinoline

Prepared by treating 3-methoxy-1-methyl-isoquinoline with sulfuryl chloride in methylene chloride.

Rf value: 0.30 (silica gel, cyclohexane)

Mass Spectrum (ESI⁺): m / z = 208, 210 [M + H]⁺

&gt; Example LXX

-cvklopropyl-8-bromo xanthine

Prepared by reaction of 3-cyclopropyl-xanthine with bromine in the presence of potassium carbonate in acetonitrile at 60 ° C.

Rf value: 0.65 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 1)

Mass Spectrum (ESI⁺): m / z = 271, 273 [M + H]⁺

Example LXXI

Ethyl .2.3.4-tetrahydro-phenanthridine-6-yl-carboxylate

By analogy with the method described by Gonsalves et al. (Tetrahedron 1992, 48, 6821), becomes a solution of 3.90 g of ethyl 5,6,7,8-tetrahydrobenzo [1,2,4] triazine-3-carboxylate (Sagi et al., Heterocycles 1989 , 29, 2253) in 20 ml of refluxed dioxane. Then, 8.22 g of anthranilic acid and 7.02 g of isoamyl nitrite, both dissolved in 20 ml of dioxane, are added dropwise over 25 minutes by means of two drip funnels. The reaction mixture is refluxed for a further 30 minutes. For working up, the cooled dark brown reaction solution is diluted with 150 ml of diethyl ether, washed with 100 ml of 2 N sodium hydroxide solution and water, dried over magnesium sulfate and evaporated. The brown oily flask residue is chromatographed through a silica gel column with ethyl acetate / petroleum ether (20:80 to 50:50) as the eluant. The product obtained is still somewhat contaminated but is continued to be sold without further purification.

Yield: 380 mg (8% of theoretical value)

Rf value: 0.55 (silica gel, petroleum ether / ethyl acetate = 2: 1)

Mass Spectrum (ESI⁺): m / z = 256 [M + H]⁺

133

Preparation of final compounds:

Example 1,1,3-dimethyl-7- (2,6-dicano-benzyl) -8- (3-amino-piperidin-1-yl) -xanthine

129 3 mg of 3-amino-piperidine dihydrochloride is added to a mixture of 298 mg of 1,3-dimethyl-7 (2,6-dicyano-benzyl) -8-bromo-xanthine and 420 mg of potassium carbonate in 9 ml of N, N-dimethylformamide. . The reaction mixture is stirred for three hours at 80 ° C. For working up, the mixture is diluted with methylene chloride and washed with saturated sodium chloride solution. The organic phase is dried over magnesium sulfate and evaporated. The crude product is purified by chromatography through a silica gel column with methylene chloride / methanol / conc. methanolic ammonia (95: 5: 1 to 80: 20: 1) as eluent.

Yield: 43 mg (14% of theoretical value)

Rf value: 0.67 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 80: 20: 1) Mass Spectrum (ESI⁺): m / z = 419 [M + H]⁺

The following compounds are obtained analogously to Example 1:

(1) 1- (2-Cyano-ethyl) -3-methyl-7- (2-cyano-benzyl) -8- (3-amino-piperidin-1-yl) -xanthine Rf: 0.35 ( silica gel, methylene chloride / methanol = 9: 1)

Mass Spectrum (ESI⁺): m / z = 433 [M + H]⁺

Example 2 1- (2- {2 - [(Ethoxycarbonyl) methoxy] phenyl} -2-oxo-ethyl) -3-methyl-7- (3-methyl-2-buten-1-yl) 8- (3 -amino-piperidin-1-yl-xanthine

A solution of 209 mg of 1- (2- {2 - [(ethoxycarbonyl) methoxy] phenyl} -2-oxo-ethyl) -3-methyl-7 (3-methyl-2-buten-1-yl) -8 - [3- (tert-Butyloxycarbonylamino) -piperidin-1-yl] -xanthine in 4 ml of methylene chloride is combined with 1 ml of trifluoroacetic acid and stirred for half an hour at ambient temperature. For working up, the reaction mixture is diluted with methylene chloride and washed with saturated potassium carbonate solution. The organic phase is dried, evaporated and chromatographed through a silica gel column with methylene chloride / methanol (1: 0 to 4: 1) as eluent.

Yield: 153 mg (87% of theoretical value)

Mass Spectrum (ESI⁺): m / z = 553 [M + H]⁺

134

The following compounds are obtained analogously to Example 2:

(1) 1- (2- {2 - [(aminocarbonyl) methoxy] -phenyl} -2-oxo-ethyl) -3-methyl-7- (3-methyl-2-buten-1-yl) -8- ( 3-amino-piperidin-1-yl) -xanthine

Mass Spectrum (ESI⁺): m / z = 524 [M + H]⁺ (2) 1- (2- {3 - [(methanesulfonyl) methoxy] phenyl} -2-oxo-ethyl) -3-methyl-7- (3-methyl-2-butenyl) -8- (3 -amino-piperidin-1-yl) -xanthine

Rf value: 0.58 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 100: 100: 0.1)

Mass Spectrum (ESI⁺): m / z = 543 [M + H]⁺ (3) 1- (1-Methyl-2-oxo-2-phenyl-ethyl) -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidine-1-yl) 1-yl) -xanthine

Mass Spectrum (ESI⁺): m / z = 465 [M + H]⁺ (4) 1- (2-Phenoxy-ethyl) -3-methyl-7- (2-cyano-benzyl) -8- (3-amino-piperidin-1-yl) -xanthine Rf: 0.50 ( silica gel, methylene chloride / methanol = 9: 1)

Mass Spectrum (ESI⁺): m / z = 500 [M + H]⁺ (5) 1- (2-Phenyl-2-oxo-ethyl) -7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine R value: 0.58 (silica gel, methylene chloride / methanol / conc. aqueous ammonia = 80: 20: 1) Mass Spectrum (EST): m / z = 435 [MH] '(6) 1- (2- {3 - [( ethoxycarbonyl) methoxy-phenyl} -2-oxo-ethyl) -3-methyl-7- (3-methyl-2-butenyl) -8- (3-amino-piperidin-1-yl) -xanthine

Mass Spectrum (ESI⁺): m / z = 553 [M + H]⁺ (7) 1- (2- {2 - [(methylaminocarbonyl) methoxy] phenyl} -2-oxoethyl) -3-methyl-7- (3-methyl-2butene-1-yl) - 8- (3 -amino-piperidin-1-yl) -xanthine Mass Spectrum (ESI⁺): m / z = 538 [M + H]⁺

135 (8) 1- (2- {2 - [(Dimethylaminocarbonyl) methoxy] phenyl} -2-oxoethyl) -3-methyl-7- (3-methyl-2butene-1-yl) - 8- (3 -amino-piperidin-1-yl) -xanthine

Mass Spectrum (ESI⁺): m / z = 552 [M + H]⁺ (9) 1- (2-Methoxy-ethyl) -3-methyl-7- (2-cyano-benzyl) -8- (3-amino-piperidin-1-yl) -xanthine Rf value: 0.40 ( silica gel, methylene chloride / methanol = 9: 1)

Mass Spectrum (ESI⁺): m / z = 438 [M + H]⁺ (10) 1-methyl-3 - [(methoxycarbonyl) methyl] -7- (2-cyano-benzyl) -8- (3-amino-piperidin-1-yl) xanthine

Rf value: 0.40 (silica gel, methylene chloride / methanol = 9: 1)

Mass Spectrum (ESI⁺): m / z = 452 [M + H]⁺ (11) 1-Methyl-3-cyanomethyl-7- (2-cyano-benzyl) -8- (3-amino-piperidin-1-yl) -xanthine (Made with 5-6M isopropanolic hydrochloric acid in methylene chloride)

Rf value: 0.20 (silica gel, methylene chloride / methanol = 9: 1)

Mass Spectrum (ESI⁺): m / z = 419 [M + H]⁺ (12) 1-Methyl 1-3- (2-propyn-1-yl) -7- (2-cyano-benzyl) -8- (3-amino-piperidin-1-yl) -xanthine Rf value: 0 40 (silica gel, methylene chloride / methanol = 9: 1)

Mass Spectrum (ESI⁺): m / z = 418 [M + H]⁺ (13) 1- {2- [3- (2-Oxo-imidazolidin-1-yl) -phenyl] -2-oxo-ethyl} -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

Rf value: 0.54 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 100: 100: 0.1)

Mass Spectrum (ESI⁺): m / z = 535 [M + H]⁺ (14) 1-methyl-3- (2-propen-1-yl) -7- (2-cyano-benzyl) -8- (3-amino-piperidin-1-yl) -xanthine Rf value: 0, 40 (silica gel, methylene chloride / methanol = 9: 1)

Mass Spectrum (ESI⁺): m / z = 420 [M + H]⁺

136 (15) 1- (2-Phenyl-2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine Mass Spectrum ( ESI⁺): m / z = 435 [M + H]⁺ (16) 1- (2- {2 - [(Ethylcarbonyl) amino] phenyl} -2-oxo-ethyl) -3-methyl-7- (3-methyl-2-buten-1-yl) 8- ( 3-amino-piperidin-1-yl) -xanthine

Rf value: 0.50 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 100: 100: 0.1)

Mass Spectrum (ESI⁺): m / z = 522 [M + H]⁺ (17) 1-Methyl-3-phenyl-7- (2-cyano-benzyl) -8- (3-amino-piperidin-1-yl) -xanthine

Rf value: 0.40 (silica gel, methylene chloride / methanol = 9: 1)

Mass Spectrum (ESI⁺): m / z = 456 [M + H]⁺ (18) 1- [2- (2-Amino-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8 - ((5) - 3-aminopiperidin-1-yl) -xanthine

Rf value: 0.50 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 0.1)

Mass Spectrum (ESI⁺): m / z = 466 [M + H]⁺ (19) 1- (2-Phenyl-2-oxo-ethyl) -3-cyanomethyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidinl-yl) -xanthine

Rf value: 0.07 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass spectrum (ESI⁺): m / z = 476 [M + H]⁺ (20) 1 - [(quinolin-2-yl) methyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) xanthine (Made with 5-6 M isopropanolic hydrochloric acid in methylene chloride)

Rf value: 0.50 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 474 [M + H]⁺ (21) 1 - [(2-oxo-27β-chromomen-4-yl) methyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-aminopiperidin-2-yl) 1-yl) -xanthine (Made with 5-6 M isopropanolic hydrochloric acid in methylene chloride)

137

Mass Spectrum (ESI⁺): m / z = 491 [M + H]⁺

Rf value: 0.16 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 95: 5: 0.1) (22) 1 - [(cinnolin-4-yl) methyl] -3-methyl-7- ( 3-Methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine (1: 1 mixture with 1 - [(1,4-dihydro-cinnolin-4-yl) methyl) ] -3-Methyl-7- (3-methyl-2butene-1-yl) - 8- (3-amino-piperidin-1-yl) -xanthine) (Done with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.49 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass spectrum (ESI⁺): m / z - 475 [M + H]⁺ (23) 1 - [(1-methyl-2-oxo-1,2-dihydro-quinolin-4-yl) methyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8 - (3-Amino-piperidin-1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Melting point: 178-181 ° C

Mass Spectrum (ESI⁺): m / z = 504 [M + H]⁺ (24) 1 - [(4-oxo-3,4-dihydro-phthalazin-1-yl) methyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- ( 3 amino-piperidin-1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.06 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 95: 5: 0.1) Mass Spectrum (ESI⁺): m / z = 491 [M + H]⁺ (25) 1 - [(quinazolin-4-yl) methyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.48 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 475 [M + H]⁺ (26) 1 - [(5-methyl-3-phenyl-isoxazol-4-yl) methyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3 amino-piperidine -1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.40 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 0.1) Mass spectrum (ESI⁺): m / z = 504 [M + H]⁺

138 (27) 1 - [(isoquinolin-3-yl) methyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.51 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass spectrum (ESI⁺): m / z = 474 [M + H]⁺ (28) 1 - [(3-phenyl- [1,2,4] oxadiazol-5-yl) methyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- ( 3 amino-piperidin-1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.23 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 95: 5: 1) Mass spectrum (ESI⁺): m / z = 491 [M + H]⁺ (29) 1 - [(4-phenyl-pyridin-2-yl) methyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-aminopiperidin-1-yl) xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.51 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia - 90: 10: 1) Mass spectrum (ESI⁺): m / z = 500 [M + H]⁺ (30) 1 - [(5-phenyl-pyridin-2-yl) methyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-aminopiperidin-1-yl) xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.58 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 500 [M + H]⁺ (31) 1 - [(3-methyl-4-oxo-3,4-dihydro-phthalazin-1-yl) methyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8 - (3 ~ amino-piperidin-1-yl) -xanthine hydrochloride (Done with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride; the product precipitated as the hydrochloride)

Rf value: 0.55 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 0.1) Mass Spectrum (ESI⁺): m / z = 505 [M + H]⁺

139 (32) 1- [2- (3-methylsulfanyl-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidine) -1-yl) -xanthine

Rf value: 0.34 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass spectrum (ESI⁺): m / z = 497 [M + H]⁺ (33) 1- [2- (3-Methanesulfinyl-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidine -1-yl) -xanthine

Rf value: 0.21 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 513 [M + H]⁺ (34) 1- [2- (3-Methanesulfonyl-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidine-1-yl) 1-yl) -xanthine

Rf value: 0.66 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 1)

Mass Spectrum (ESI⁺): m / z = 529 [M + H]⁺ (35) 1- [2- (3-Carboxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-aminopiperidine - 1-yl) -xanthine hydrochloride (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride; the product precipitated as the hydrochloride)

Rf value: 0.54 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 1)

Mass Spectrum (ESI⁺): m / z = 495 [M + H]⁺ (36) 1- [2- (3-Methoxycarbonyl-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3 amino) piperidin-1-yl) -xanthine hydrochloride (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride; the product precipitated as the hydrochloride)

Rf value: 0.47 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 1)

Mass Spectrum (ESI⁺): m / z = 509 [M + H]⁺

140 (37) 1- {2- [3- (methylaminocarbonyl) phenyl] -2-oxo-ethyl} -3-methyl-7- (3-methyl-2-buten-1-yl) 8- (3-amino) -piperidin-1-yl) -xanthine hydrochloride (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride; the product obtained as the hydrochloride)

Rf value: 0.53 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 1)

Mass Spectrum (ESI⁺): m / z = 508 [M + H]⁺ (38) 1- {2- [3- (Dimethylaminocarbonyl) -phenyl] -2-oxo-ethyl} -3-methyl-7- (3-methyl-2-butenyl) -8- (3-amino piperidin-1-yl) -xanthine hydrochloride (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride; the product obtained as the hydrochloride)

Rf value: 0.53 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 1)

Mass Spectrum (ESI⁺): m / z = 522 [M + H]⁺ (39) 1- {2- [3- (Morpholin-4-yl-carbonyl) -phenyl] -2-oxo-ethyl} -3-methyl-7- (3-methyl-1-2-buten-1-yl) ) -8- (3-amino-piperidin-1-yl) -xanthine hydrochloride (Done with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride; the product obtained as the hydrochloride)

Rf value: 0.53 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 1)

Mass Spectrum (ESI⁺): m / z = 564 [M + H]⁺ (40) 1- [2- (2-Carboxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-aminopiperidine 1-yl) -xanthine hydrochloride (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride; the product obtained as the hydrochloride)

Rf value: 0.53 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 1)

Mass Spectrum (ESI⁺): m / z = 495 [M + H]⁺

141 (41) 1- [2- (2-Ethoxycarbonyl-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3 amino-piperidinyl) 1-yl) -xanthine hydrochloride (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride; the product obtained as the hydrochloride)

Rf value: 0.41 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 1)

Mass Spectrum (ESI⁺): m / z = 523 [M + H]⁺ (42) 1- {2- [2- (Dimethylaminocarbonyl) -phenyl] -2-oxo-ethyl} -3-methyl-7- (3-methyl-2-butenyl) -8- (3-amino) piperidin-1-yl) -xanthine hydrochloride (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride; the product obtained as the hydrochloride)

Rf value: 0.53 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 1)

Mass Spectrum (ESI⁺): m / z = 522 [M + H]⁺ (43) 1- {2- [2- (Morpholin-4-yl-carbonyl) -phenyl] -2-oxo-ethyl} -3-methyl-7- (3-methyl-1-2-buten-1-yl) ) -8 '(3-Amino-piperidin-1-yl) -xanthine hydrochloride (Done with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride; the product obtained as the hydrochloride)

Rf value: 0.53 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 1)

Mass Spectrum (ESI⁺): m / z = 564 [M + H]⁺ (44) 1- [2- (2,6-Dimethoxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3 amino) piperidin-1-yl) -xanthine hydrochloride (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride; the product obtained as the hydrochloride)

Rf value: 0.44 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 1)

Mass Spectrum (ESI⁺): m / z = 511 [M + H]⁺

142 (45) 1- (2-Phenyl-2-oxo-ethyl) -3-methyl-7- (2,3-dimethyl-2-buten-1-yl) -8- (3-amino-piperidinyl) -xanthine hydrochloride (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride; the product obtained as the hydrochloride)

Rf value: 0.68 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 1)

Mass Spectrum (ESI⁺): m / z = 465 [M + H]⁺ (46) 1- ((E) -3-Phenyl-allyl) -3-methyl-7- (3-methyl-2-buten-1-yl) - 8- (3-amino-piperidin-1-yl) xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.38 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 95: 5: 0.1) Mass Spectrum (ESI⁺): m / z = 449 [M + H]⁺ (47) 1 - [(benzo [Z&gt;] thiophen-3-yl) methyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-aminopiperidin-1-yl) yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.51 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass spectrum (ESI⁺): m / z = 479 [M + H]⁺ (48) 1 - [(17β-indol-3-yl) methyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) ) xanthine

Rf value: 0.48 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 462 [M + H]⁺ (49) 1 - [(biphenyl-4-yl) methyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.30 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 95: 5: 0.1) Mass Spectrum (ESI⁺): m / z = 499 [M + H]⁺ (50) 1 - [(1-Naphthyl) methyl] -3-methyl-7- (2-butyn-1-yl) - 8- (3-amino-piperidin-1-yl) -xanthine (Done with 5- 6 M isopropanol-containing hydrochloric acid in methylene chloride)

143

Rf value: 0.56 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 457 [M + H]⁺ (51) 1 - [(1-methyl-2-oxo-1,2-dihydro-quinolin-4-yl) methyl] -3-methyl-7- (2-butyn-1-yl) - 8- (3 amino-piperidin-1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.40 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 488 [M + H]⁺ (52) 1 - [(Quinolin-4-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine (Done with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.52 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 458 [M + H]⁺ (53) 1- (2-Cyclohexyl-2-oxo-ethyl) -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-aminopiperidin-1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.48 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 457 [M + H]⁺ (54) 1- (3,3-Dimethyl-2-oxo-butyl) -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidinl-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.49 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia - 90: 10: 1) Mass spectrum (ESI⁺): m / z = 431 [M + H]⁺ (55) 1 - [(Quinazolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine (Done with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.20 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 95: 5: 0.1) Mass spectrum (ESI⁺): m / z = 459 [M + H]⁺ (56) 1 - [(2-methyl-naphthalen-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

144 (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.25 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 95: 5: 0.1) Mass spectrum (ESI⁺): m / z = 471 [M + H]⁺ (57) 1- ({5 - [(methoxycarbonyl) methylamino] -isoquinolin-1-yl} methyl) -3-methyl-7- (3-methyl-2-buten-1-yl) - 8- (3-amino) piperidin-1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.43 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass spectrum (ESI⁺): m / z = 561 [M + H]⁺ (58) 1- (2-Dimethylamino-2-oxo-ethyl) -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-aminopiperidin-1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.38 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 418 [M + H]⁺ (59) 1- [2- (piperidin-1-yl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-aminopiperidine - 1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.35 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 458 [M + H]⁺ (60) 1 - [(2-methyl-1-oxo-1,2-dihydro-isoquinolin-4-yl) methyl] -7- (2-butyn-1-yl) - 8- (3-aminopiperidine-1 -yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.17 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 95: 5: 0.1) Mass spectrum (ESI⁺): m / z = 488 [M + H]⁺ (61) 1 - [(2-methyl-1-oxo-1,2-dihydro-isoquinolin-4-yl) methyl] -7- (3-methyl-2-buten-1-yl) -8- (3 amino-piperidin-1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.13 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 95: 5: 0.1) Mass spectrum (ESI⁺): m / z = 504 [M + H]⁺

145 (62) 1 - [(2-methoxy-naphthalen-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) - 8- (3-amino-piperidin-1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.17 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 95: 5: 0.1) Mass spectrum (ESI⁺): m / z = 487 [M + H]⁺ (63) 1 - [(isoquinolin-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine (Done with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.42 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia - 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 458 [M + H]⁺ (64) 1 - [(4-methoxy-naphthalen-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) - 8- (3-amino-piperidin-1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.14 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 95: 5: 0.1) Mass Spectrum (ESI⁺): m / z - 487 [M + H]⁺ (65) 1 - [(3-methyl-isoquinolin-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Melting point: 155-158 ° C

Mass Spectrum (ESI⁺): m / z = 472 [M + H]⁺ (66) 1- [2- (2,3-Dimethoxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3 amino) piperidin-1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.40 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 511 [M + H]⁺ (67) 1 - [(5-nitro-naphthalen-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

146

Rf value: 0.15 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 95: 5: 0.1) Mass Spectrum (ESI⁺): m / z = 502 [M + H]⁺ (68) 1- [2- (pyrrolidin-1-yl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-aminopiperidin-1-yl) 1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.56 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 444 [M + H]⁺ (69) 1 - [(4-methyl-isoquinolin-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) - 8- (3-amino-piperidin-1-yl) - xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.46 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 472 [M + H]⁺ (70) 1 - [(2-naphthyl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine (Done with 5- 6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.20 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 95: 5: 0.1) Mass spectrum (ESI⁺): m / z = 457 [M + H]⁺ (71) 1 - [(4-oxo-3,4-dihydroquinazolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-aminopiperidin-1) -yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.38 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 0.1) Mass Spectrum (ESI⁺): m / z = 475 [M + H]⁺ (72) 1 - [(Quinolin-6-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine (Done with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.15 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 95: 5: 0.1) Mass Spectrum (ESI⁺): m / z = 458 [M + H]⁺ (73) 1 - [(4-Dimethylamino-naphthalen-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) - 8- (3-aminopiperidin-1-yl) -xanthine

147 (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.18 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 95: 5: 0.1) Mass Spectrum (ESI⁺): m / z = 500 [M + H]⁺ (74) 1 - [(isoquinolin-1-yl) methyl] -3-methyl-7 - ((E) -2-buten-1-yl) -8 - (3-amino-piperidin-1-yl) xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride; the product still contains about 20% Z isomer)

Rf value: 0.66 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 0.1) Mass Spectrum (ESI⁺): m / z = 460 [M + H]⁺ (75) 1 - [(3-Methoxy-naphthalen-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.25 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 95: 5: 0.1) Mass spectrum (ESI⁺): m / z = 487 [M + H]⁺ (76) 1- [2- (2,3-dihydro-benzo [1,4] dioxin-5-yl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-butene) 1-yl) -8- (3-amino-piperidin-1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Mass Spectrum (ESI⁺): m / z = 509 [M + H]⁺ (77) 1- [(3-methyl-4-oxo-3,4-dihydroquinazolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3amino) -piperidin-1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.20 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 95: 5: 0.1) Mass spectrum (ESI⁺): m / z = 489 [M + H]⁺ (78) 1- [2- (3-Methyl-2-oxo-2,3-dihydro-benzoxazol-7-yl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-butene -1-yl) -8- (3-amino-piperidin-1-yl) -xanthine (Made with 5-6M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.47 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 522 [M + H]⁺

148 (79) 1- [2- (Benzo [1,3] dioxol-4-yl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8 - (3 amino-piperidin-1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Mass Spectrum (ESI⁺): m / z = 495 [M + H]⁺ (80) 1 - [(quinazolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((7?) -3-amino-piperidin-1-yl xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Mass Spectrum (ESI⁺): m / z - 459 [M + H]⁺ (81) 1 - [(quinazolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((5) -3-amino-piperidin-1-yl) xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Mass Spectrum (ESI⁺): m / z = 459 [M + H]⁺ (82) 1 - [(quinazolin-2-yl) methyl] -3-methyl-7 - ((E) -2-buten-1-yl) -8 - ((5) -3-amino-piperidin-1 yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride; the product still contains about 20% Z-isomer)

Rf value: 0.12 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 95: 5: 0.1) Mass Spectrum (ESI⁺): m / z = 461 [M + H]⁺ (83) 1 - [(quinazolin-2-yl) methyl] -3-methyl-7 - ((E) -2-buten-1-yl) -8 - ((R) -3-amino-piperidin-1yl xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride; the product still contains about 15% Z-isomer)

Rf value: 0.12 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 95: 5: 0.1) Mass Spectrum (ESI⁺): m / z = 461 [M + H]⁺ (84) 1 - [(3-methyl-isoquinolin-1-yl) methyl] -3-methyl-7 - ((E) -2-buten-1-yl) -8 - ((7?) - 3- aminopiperidin-1-yl) -xanthine

149 (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride; the product still contains about 17% Z isomer)

Rf value: 0.54 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 474 [M + H]⁺ (85) 1 - [(3-methyl-isoquinolin-1-yl) methyl] -3-methyl-7 - ((E) -2-buten-1-yl) -8 - ((5) -3-aminopiperidine -1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride; the product still contains about 17% Z-isomer)

Rf value: 0.54 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia - 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 474 [M + H]⁺ (86) 1- (2- {2 - [(Ethylaminocarbonyl) methoxy] phenyl} -2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) 8 - ((7?) -3-amino-piperidin-1-yl) -xanthine

Mass Spectrum (ESI⁺): m / z = 536 [M + H]⁺ (87) 1- [2- (2-Amino-phenyl) -2-oxo-ethyl] -3-methyl-7 - [(1-cyclopenten-1-yl) methyl] -8- (3-aminopiperidin-1 yl) xanthine

Mass Spectrum (ESI⁺): m / z = 478 [M + H]⁺ (88) 1- (2-Phenyl-2-oxo-ethyl) -3-methyl-7 - [(1-cyclopenten-1-yl) methyl] -8- (3-amino-piperidinl-yl) -xanthine

Mass Spectrum (ESI⁺): m / z = 463 [M + H]⁺ (89) 1- (2- {2 - [(methylaminocarbonyl) methoxy] phenyl} -2-oxoethyl) -3-methyl-7- [(1 cyclopenten-1-yl) methyl] -8- (3 -amino-piperidin-1-yl) -xanthine Mass Spectrum (ESI⁺): m / z = 550 [M + H]⁺ (90) 1-Methyl 1-3-isopropyl-7- (2-cyano-benzyl) -8- (3-amino-piperidin-1-yl) -xanthine Rf: 0.40 (silica gel, methylene chloride / methanol = 9: 1)

Mass Spectrum (ESI⁺): m / z = 422 [M + H]⁺

150 (91) 1- (2- {2 - [(methylaminocarbonyl) methoxy] phenyl} -2-oxoethyl) -3-methyl-7- (2-butynyl) -8- (3-amino-piperidine) -1-yl) -xanthine Mass Spectrum (ESI⁺): m / z = 522 [M + H]⁺ (92) 1- (2- {2 - [(aminocarbonyl) methoxy] -phenyl} -2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8 (3-amino) piperidin-1-yl) -xanthine Mass Spectrum (ESI⁺): m / z = 508 [M + H]⁺ (93) 1- [2- (2-Cyanomethylamino-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (310 amino-piperidine -1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.50 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 1)

Mass Spectrum (ESI⁺): m / z = 505 [M + H]⁺ (94) 1- (2- {2 - [(isopropylaminocarbonyl) methoxy] -phenyl} -2-oxo-ethyl) -3-methyl-7- (2-butynl-yl) -8- (3-amino-piperidine) (1-yl) -xanthine

Rf value: 0.30 (silica gel, methylene chloride / methanol = 9: 1)

Mass Spectrum (ESI⁺): m / z = 550 [M + H]⁺ (95) 1 - [(isoquinolin-1-yl) methyl] -3 - [(methoxycarbonyl) methyl] -7- (3-methyl-2-buten-1-yl) -8 (3-amino-piperidine-1 yl) xanthine

Rf value: 0.21 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 532 [M + H]⁺ (96) 1- [2- (2-Acetylamino-phenyl) -2-oxo-ethyl] -3-methyl-7 - ((E) -2-buten-1-yl) -8- (3-aminopiperidin-2-yl) 1-yl) -xanthine (the product contains about 10% Z-isomer)

Mass Spectrum (ESI⁺): m / z = 494 [M + H]⁺ (97) 1- (2-Phenyl-2-oxo-ethyl) -3-methyl-7 - ((E) -2-buten-1-yl) -8- (3-amino-piperidin-1-yl) xanthine (the product contains about 25% Z-isomer)

151

Rf value: 0.30 (silica gel, methylene chloride / methanol = 9: 1)

Mass Spectrum (ESI⁺): m / z = 437 [M + H]⁺ (98) 1- (2- {2 - [(isopropyloxycarbonyl) methoxy] phenyl} -2-oxoethyl) -3-methyl-7- (3-methyl-buten-1-yl) - 8- ( 3-amino-piperidin-1-yl) -xanthine

Mass Spectrum (ESI⁺): m / z = 567 [M + H]⁺ (99) 1- (2- {2 - [(methylaminocarbonyl) methoxy] -phenyl} -2-oxo-ethyl) -3-methyl-7- (2-butynyl) -8 - ((7?) - 3-amino-piperidin-l-yl) xanthine

Mass Spectrum (ESI⁺): m / z - 522 [M + H]⁺ (100) 1- (2- {2 - [(isopropylcarbonyl) amino] -phenyl} -2-oxo-ethyl) -3-methyl-7 - ((E) -2-buten-1-yl) -8- ( 3-amino-piperidin-1-yl) -xanthine (the product contains about 10% Z-isomer)

Mass Spectrum (ESI⁺): m / z = 522 [M + H]⁺ (101) 1- (2- {2 - [(methylaminocarbonyl) methoxy] phenyl} -2-oxo-ethyl) -3-methyl-7 - ((E) -2butene-1-yl) - 8- (3 -amino-piperidin-1-yl) -xanthine (the product contains about 8% Z-isomer)

Rf value: 0.51 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 0.1)

Mass Spectrum (ESI⁺): m / z = 524 [M + H]⁺ (102) 1- (2- {2 - [(ethylaminocarbonyl) methoxy] -phenyl} -2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8 - ((* S ) -3-amino-piperidin-1-yl) -xanthine

Mass Spectrum (ESI⁺): m / z = 536 [M + H]⁺ (103) 1- [2- (2- {[(Ethoxycarbonylamino) carbonyl] amino} -phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8 - (3-amino-piperidin-1-yl) xanthine

Mass Spectrum (ESI⁺): m / z = 581 [M + H]⁺ (104) 1- [2- (2-Amino-phenyl) -2-oxo-ethyl] -3-methyl-7 - ((E) -2-buten-1-yl) -8- (3-aminopiperidin-1-yl) 1-yl) -xanthine

152

Rf value: 0.54 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 0.1)

Mass Spectrum (ESI⁺): m / z = 452 [M + H]⁺ (105) 1- [2- (2-Acetylamino-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8 - ((S) - 3 amino-piperidin-1-yl) -xanthine

Rf value: 0.48 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 0.1)

Mass Spectrum (ESI⁺): m / z = 508 [M + H]⁺ (106) 1- [2- (2-Amino-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) - 8- (3-amino-piperidine-1 yl) xanthine

Rf value: 0.31 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 450 [M + H]⁺ (107) 1- (2- {2 - [(methylaminocarbonyl) methoxy] -phenyl} -2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8 - ((* S) -3-amino-piperidin-1-yl) -xanthine

Mass Spectrum (ESI⁺): m / z = 522 [M + H]⁺ (108) 1- (2-Phenyl-2-oxo-ethyl) -3-methyl-7 - ((E) -2-buten-1-yl) -8 - ((7?) -3-amino-piperidine -l-yl) xanthine (the product contains about 22% Z-isomer)

Mass Spectrum (ESI⁺): m / z = 437 [M + H]⁺ (109) 1- (2- {2 - [(ethylaminocarbonyl) methoxy] -phenyl} -2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8- (3-amino) piperidin-1-yl) -xanthine

Rf value: 0.40 (silica gel, methylene chloride / methanol = 9: 1)

Mass Spectrum (ESI⁺): m / z = 536 [M + H]⁺ (110) 1- [2- (2-Acetylamino-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-aminopiperidin-1-yl) xanthine

Rf value: 0.23 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass spectrum (ESI⁺): m / z = 492 [M + H]⁺

153 (111) 1- (2- {2- [2-oxo-2- (pyrrolidin-1-yl) -ethoxy] -phenyl} -2-oxo-ethyl) -3-methyl-7- (2-butynyl) yl) -8- (3-amino-piperidin-1-yl) -xanthine

Rf value: 0.20 (silica gel, methylene chloride / methanol = 9: 1)

Mass Spectrum (ESI⁺): m / z = 562 [M + H]⁺ (112) 1- (2- {2 - [(methylaminocarbonyl) methoxy] phenyl} -2-oxoethyl) -3-methyl-7- (3-methyl-2butene-1-yl) - 8 - (( 5) -3-Amino-piperidin-1-yl) -xanthine

Mass Spectrum (ESI⁺): m / z - 538 [M + H]⁺ (113) 1- (2-Phenyl-2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8 - ((7?) - 3-amino-piperidin-1-yl ) xanthine

Mass Spectrum (ESI⁺): m / z = 435 [M + H]⁺ (114) 1- (2- {2 - [(ethylaminocarbonyl) methoxy] phenyl} -2-oxo-ethyl) -3-methyl-7 - ((E) -2-buten1-yl) -8 - (( 7- (3-Amino-piperidin-1-yl) -xanthine (the product contains about 30% Z-isomer)

Mass Spectrum (ESI⁺): m / z = 538 [M + H]⁺ (115) 1-Methyl-7- (2-cyano-benzyl) -8- (3-amino-piperidin-1-yl) -xanthine

Mass Spectrum (ESI⁺): m / z = 380 [M + H]⁺ (116) 1- (2- {2 - [(isopropylcarbonyl) amino] phenyl} -2-oxoethyl) -3-methyl-7- (3-methyl-2butene-1-yl) - 8- (3 -amino-piperidin-1-yl) -xanthine

Rf value: 0.40 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 0.1)

Mass Spectrum (ESI⁺): m / z = 536 [M + H]⁺ (117) 1- (2-Phenyl-2-oxo-ethyl) -3-methyl-7 - ((E) -2-buten-1-yl) -8 - ((5) -3-amino-piperidine -1-yl) xanthine (the product contains about 23% Z-isomer)

Rf value: 0.42 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 0.1)

154

Mass Spectrum (ESI⁺): m / z = 437 [M + H]⁺ (118) 1- (2- {2 - [(isopropylcarbonyl) amino] -phenyl} -2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8 (3-amino) piperidin-1-yl) -xanthine

Rf value: 0.20 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 520 [M + H]⁺ (119) 1- [2- (2-Acetylamino-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((S) -3-aminopiperidine 1-yl) -xanthine

Rf value: 0.15 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia - 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 492 [M + H]⁺ (120) 1- (2- {2 - [(isopropylcarbonyl) amino] phenyl} -2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8 ((S) - 3-amino-piperidin-1-yl) -xanthine

Mass Spectrum (ESI⁺): m / z = 520 [M + H]⁺ (121) 1- (2-Phenyl-2-oxo-ethyl) -3-methyl-7- (2-methyl-allyl) -8- (3-amino-piperidin-1-yl) -xanthine Rf value: 0.21 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 437 [M + H]⁺ (122) 1- (2-Phenyl-2-oxo-ethyl) -3-methyl-7- (3-bromo-allyl) -8- (3-amino-piperidin-1-yl) -xanthine Rf 0.14 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 501, 503 [M + H]⁺ (123) 1- (2- {2 - [(methoxycarbonyl) amino] phenyl} -2-oxo-ethyl) -3-methyl-7- (3-methyl-2-butenyl) -8- (3 -amino-piperidin-1-yl) -xanthine

Rf value: 0.42 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 0.1)

Mass Spectrum (ESI⁺): m / z = 524 [M + H]⁺ (124) 1- (2-Phenyl-2-oxo-ethyl) -3-methyl-7 - [(furan-2-yl) methyl] -8- (3-amino-piperidin-1-yl) xanthine

Rf value: 0.23 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1)

155

Mass Spectrum (ESI⁺): m / z = 463 [M + H]⁺ (125) 1- (2-Phenyl-2-oxo-ethyl) -3-methyl-7- (2-chloro-allyl) -8- (3-amino-piperidin-1-yl) -xanthine Rf 0.18 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) (126) 1- {2- [2- (1-methoxycarbonyl-ethoxy) -phenyl] -2-oxo-ethyl} - 3-methyl-7- (2-butyn-1-yl) 8- (3-amino-piperidin-1-yl) -xanthine

Mass Spectrum (ESI⁺): m / z = 537 [M + H]⁺ (127) 1- {2- [2- (1-Aminocarbonyl-ethoxy) -phenyl] -2-oxo-ethyl} -3-methyl-7- (2-butyn-1-yl) -8 (3-amino) -piperidin-1-yl) -xanthine

Mass Spectrum (ESI⁺): m / z = 522 [M + H]⁺ (128) 1- (2-Phenyl-2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8 - ((S) -3-amino-piperidin-1-yl) xanthine

Mass Spectrum (ESI⁺): m / z = 435 [M + H]⁺ (129) 1- [(3-methyl-isoquinolin-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((S) -3-aminopiperidin-1 - yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Melting point: 155-156.5 ° C

Mass Spectrum (ESI⁺): m / z = 472 [M + H]⁺ (130) 1 - [(3-methyl-isoquinolin-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-aminopiperidin-1-yl xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.52 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 472 [M + H]⁺ (131) 1 - [(4-methyl-isoquinolin-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) - 8 - ((O) -3-aminopiperidin-1-yl xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.46 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1)

156

Mass Spectrum (ESI⁺): m / z = 472 [M + H]⁺ (132) 1 - [(4-methyl-isoquinolin-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((5) -3-aminopiperidin-1-yl xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.46 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 472 [M + H]⁺ (133) 1 - [(4-methyl-isoquinolin-1-yl) methyl] -3-methyl-7 - ((E) -2-buten-1-yl) -8 - ((5) -3-aminopiperidine -1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.48 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 474 [M + H]⁺ (134) 1 - [(4-methyl-isoquinolin-1-yl) methyl] -3-methyl-7 - ((E) -2-buten-1-yl) -8 - ((5) -3-aminopiperidine -1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Melting point: 167.5-172 ° C

Mass Spectrum (ESI⁺): m / z = 474 [M + H]⁺ (135) 1- [2- (2,3-dihydro-benzo [1,4] dioxin-5-yl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 (3- (5) -amino-piperidin-1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.34 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass spectrum (ESI⁺): m / z = 493 [M + H]⁺ (136) 1- [2- (2,3-dihydro-benzo [1,4] dioxin-5-yl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 (3- (5) -amino-piperidin-1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Mass Spectrum (ESI⁺): m / z = 493 [M + H]⁺ (137) 1 - [(4-methoxy-naphthalen-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((S) -3-aminopiperidin-1-yl) yl) xanthine

157 (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.52 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 487 [M + H]⁺ (138) 1 - [(4-methoxy-naphthalen-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-aminopiperidin-1-yl xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.52 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z - 487 [M + H]⁺ (139) 1- [2- (Benzo [1,3] dioxol-4-yl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R 3-Aminopiperidin-1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.41 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 479 [M + H]⁺ (140) 1- [2- (Benzo [1,3] dioxol-4-yl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((5) 3-Aminopiperidin-1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Mass Spectrum (ESI⁺): m / z = 479 [M + H]⁺ (141) 1 - [(4-methyl-quinazolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3- (5) -aminopiperidin-1-yl) xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.51 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass spectrum (ESI⁺): m / z = 473 [M + H]⁺ (142) 1 - [(4-methyl-quinazolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3- (R) -aminopiperidin-1-yl) xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Melting point: 198-202 ° C

Mass Spectrum (ESI⁺): m / z = 473 [M + H]⁺

158 (143) 1- [2- (3-Methyl-2-oxo-2,3-dihydro-benzooksazol-4-yl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2'-butene) 1-yl) -8- (3-amino-piperidin-1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.53 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1)

Mass Spectrum (ESI⁺): m / z = 522 [M + H]⁺ (144) 1- (2- {2 - [(ethylaminocarbonyl) methoxy] -phenyl} -2-oxo-ethyl) -3-methyl-7 - ((E) -2-buten1-yl) -8 - (( 5) -3-amino-piperidin-1-yl) -xanthine

Mass Spectrum (ESI⁺): m / z - 538 [M + H]⁺ (145) 1- (2- {2 - [(isopropylcarbonyl) amino] -phenyl} -2-oxo-ethyl) -3-methyl-7 - ((E) -2-buten-1-yl) -8- ( (5) -3-Amino-piperidin-1-yl) -xanthine

Rf value: 0.49 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 0.1)

Mass Spectrum (ESI⁺): m / z = 522 [M + H]⁺ (146) 1- (2- {2 - [(Ethylcarbonyl) amino] -phenyl} -2-oxo-ethyl) -3-methyl-7 - ((E) -2-buten-1-yl) -8 ( (5) -3-Amino-piperidin-1-yl) -xanthine

Mass Spectrum (ESI⁺): m / z = 508 [M + H]⁺ (147) 1- [2- (2-Acetylamino-phenyl) -2-oxo-ethyl] -3-methyl-7 - ((E) -2-buten-1-yl) -8 - ((5) - 3 amino-piperidin-1-yl) -xanthine

Mass Spectrum (ESI⁺): m / z = 494 [M + H]⁺ (148) 1- (2- {2 - [(methylaminocarbonyl) methoxy] phenyl} -2-oxo-ethyl) -3-methyl-7 - ((E) -2butene-1-yl) - 8 - (( 5) -3-Amino-piperidin-1-yl) -xanthine Mass Spectrum (ESI⁺): m / z = 524 [M + H]⁺ (149) 1- [2- (2-Acetylamino-phenyl) -2-oxo-ethyl] -3-methyl-7 - ((E) -2-buten-1-yl) -8 - ((5) - 330 amino-piperidin-1-yl) -xanthine

Rf value: 0.49 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 0.1)

Mass Spectrum (ESI⁺): m / z = 494 [M + H]⁺

159 (150) 1- (2- {2 - [(methylaminocarbonyl) methoxy] phenyl} -2-oxo-ethyl) -3-methyl-7 - ((E) -2butene-1-yl) - 8 - (( 0) -3-amino-piperidin-1-yl) -xanthine

Mass Spectrum (ESI⁺): m / z = 524 [M + H]⁺ (151) 1- (2- {2 - [(isopropylcarbonyl) amino] -phenyl} -2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8 ((7?) -3-amino-piperidin-1-yl) -xanthine

Mass Spectrum (ESI⁺): m / z = 520 [M + H]⁺ (152) 1- (2- {2 - [(isopropylcarbonyl) amino] -phenyl} -2-oxo-ethyl) -3-methyl-7 - ((E) -2-buten-1-yl) -8 ~ ( (7?) - 3-amino-piperidin-l-yl) xanthine

Mass Spectrum (ESI⁺): m / z = 522 [M + H]⁺ (153) 1- (2- {2- [2- (morpholin-4-yl) -2-oxo-ethoxy] -phenyl} -2-oxo-ethyl) -3-methyl-7- (2-butynyl) yl) 8- (3-Amino-piperidin-1-yl) -xanthine

Mass Spectrum (ESI⁺): m / z = 578 [M + H]⁺ (154) 1- (2- {2 - [(Ethylcarbonyl) amino] -phenyl} -2-oxo-ethyl) -3-methyl-7 - ((E) -2-buten-1-yl) -8 ( (5) -3-Amino-piperidin-1-yl) -xanthine

Rf value: 0.50 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 0.1)

Mass Spectrum (ESI⁺): m / z = 508 [M + H]⁺ (155) 1- (2- {2 - [(Ethylcarbonyl) amino] -phenyl} -2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8 - ((7? 3-Amino-piperidin-1-yl) -xanthine

Mass Spectrum (ESI⁺): m / z = 506 [M + H]⁺ (156) 1- (2- {2 - [(Ethylcarbonyl) amino] -phenyl} -2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8 - ((5) 3-amino-piperidin-1-yl) -xanthine

Rf value: 0.20 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 506 [M + H]⁺

160 (157) 1- [2- (2-Acetylamino-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((7?) -3-aminopiperidine -1-yl) -xanthine

Mass Spectrum (ESI⁺): m / z = 492 [M + H]⁺ (158) 1- [2- (2-nitro-3-methoxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3 amino-piperidin-1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.49 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass spectrum (ESI⁺): m / z - 526 [M + H]⁺ (159) 1- (2- {2 - [(phenylcarbonyl) amino] phenyl} -2-oxo-ethyl) -3-methyl-7 - ((E) -2-buten-1-yl) -8 ( 3-amino-piperidin-1-yl) -xanthine

Rf value: 0.49 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 0.1)

Mass Spectrum (ESI⁺): m / z = 556 [M + H]⁺ (160) 1 - [(2-acetyl-benzofuran-3-yl) methyl] -3-methyl-7- (2-butyn-1-yl) - 8- (3-amino-piperidinl-yl) -xanthine (Obtained as the main product when 1- {2- [2- (2-oxo-propoxy) -phenyl] -2-oxo-ethyl} -3-methyl7- (2-butyn-1-yl) -8- [3- (tert-Butyloxycarbonylamino) -piperidin-1-yl] -xanthine is treated with trifluoroacetic acid in methylene chloride)

Mass Spectrum (ESI⁺): m / z = 489 [M + H]⁺ (161) 1- {2- [2- (1-Ethoxycarbonyl-1-methyl-ethoxy) -phenyl] -2-oxo-ethyl} -3-methyl-7- (2-butyn1-yl) -8- ( 3-amino-piperidin-1-yl) -xanthine

Mass Spectrum (ESI⁺): m / z = 565 [M + H]⁺ (162) 1- [2- (2-Amino-3-methoxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8 (3 -amino-piperidin-1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.38 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 496 [M + H]⁺

161 (163) 1 - [(4-Dimethylaminoquinazolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-aminopiperidin-1-yl) -xanthine

Rf value: 0.30 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 0.1) Mass Spectrum (ESI⁺): m / z = 502 [M + H]⁺ (164) 1- [2- (2-oxo-2,3-dihydro-benzooksazol-7-yl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2butene-1-yl) - 8- (3-Amino-piperidin-1-yl) -xanthine

Rf value: 0.42 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass spectrum (ESI⁺): m / z - 508 [M + H]⁺ (165) 1- (2- {2 - [(Ethoxycarbonyl) methylamino] -phenyl} -2-oxo-ethyl) -3-methyl-7 - ((E) -2-buten1-yl) -8 - (( 7- (3-Amino-piperidin-1-yl) -xanthine

Rf value: 0.51 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 0.1)

Mass Spectrum (ESI⁺): m / z = 538 [M + H]⁺ (166) 1- (2-Phenyl-2-oxo-ethyl) -3-methyl-7 - ((Z) -2-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) yl) xanthine

Rf value: 0.29 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 451 [M + H]⁺ (167) 1- (2-Phenyl-2-oxo-ethyl) -3-methyl-7 - ((E) -2-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) yl) xanthine

Rf value: 0.59 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 80: 20: 1) Mass spectrum (ESI⁺): m / z = 451 [M + H]⁺ (168) 1 - [(imidazo [1,2-a] pyridin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-aminopiperidin-1-yl) xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.47 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 447 [M + H]⁺

162 (169) 1 - [(quinoxaline-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) xanthine (Done with 5 -6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.50 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 459 [M + H]⁺ (170) 1- [2- (1,3-Dimethyl-2-oxo-2,3-dihydro-1H-benzoimidazol-4-yl) -2-oxo-ethyl] -3-methyl7- (2-butyne -1-yl) - 8- (3-Amino-piperidin-1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.55 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia - 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 519 [M + H]⁺ (171) 1 - [(quinoxalin-6-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) xanthine (Done with 5 -6 M isopropanol-containing hydrochloric acid in methylene chloride)

Mass Spectrum (ESI⁺): m / z = 459 [M + H]⁺ (172) 1 - [(2-cyano-benzofuran-3-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidinl-yl) -xanthine

Mass Spectrum (ESI⁺): m / z = 472 [M + H]⁺ (173) 1- [2- (2-oxo-2,3-dihydro-benzooksazol-4-yl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) 8- (3-Amino-piperidin-1-yl) -xanthine

Mass Spectrum (ESI⁺): m / z = 492 [M + H]⁺

Rf value: 0.47 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) (174) 1 - [(3-methyl-quinoxalin-2-yl) methyl] -3-methyl-7 - (2-butyn-l-yl) -8- (3-amino-piperidin-yl) xanthine

Melting point: 188.5-191 ° C

Mass Spectrum (ESI⁺): m / z = 473 [M + H]⁺

163 (175) 1 - [(3-phenyl-isoquinolin-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) - 8- (3-amino-piperidin-1-yl) - xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.45 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 1)

Mass Spectrum (ESI⁺): m / z = 534 [M + H]⁺ (176) 1- (2- {2 - [(methanesulfinyl) methoxy] phenyl} -2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8 (3-amino) piperidin-1-yl) -xanthine x trifluoroacetic acid

Mass Spectrum (ESI⁺): m / z - 527 [M + H]⁺ (177) 1 - [(benzofuran-3-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) xanthine (Formed when 1 - {[2- (tert-butylcarbonyl) -benzofuran-3-yl] methyl} -3-methyl-7- (2-butyn-1-yl) 8- [3- (tert-butyloxycarbonylamino) -piperidine-1-yl yl] -xanthine is treated with trifluoroacetic acid in methylene chloride)

Mass Spectrum (ESI⁺): m / z - 447 [M + H]⁺ (178) 1 - [(3,4-Dimethyl-isoquinolin-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-aminopiperidin-1-yl) - xanthine hydrochloride (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.75 (alumina, methylene chloride / methanol = 10: 1)

Mass Spectrum (ESI⁺): m / z = 486 [M + H]⁺ (179) 1 - [(benzofuran-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((7?) - 3-amino-piperidin-1-yl) - xanthine

Mass Spectrum (ESI⁺): m / z = 447 [M + H]⁺ (180) 1- {[4- (morpholin-4-yl) -quinazolin-2-yl] methyl} -3-methyl-7- (2-butyn-1-yl) -8- (3-aminopiperidin-1) -yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.45 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 0.1) Mass spectrum (ESI⁺): m / z = 544 [M + H]⁺

164 (181) 1- {[4- (piperidin-1-yl) -quinazolin-2-yl] methyl} -3-methyl-7- (2-butyn-1-yl) -8- (3-aminopiperidin-1 -yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.55 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 0.1) Mass Spectrum (ESI⁺): m / z = 542 [M + H]⁺ (182) 1- {[4- (piperazin-1-yl) -quinazolin-2-yl] methyl} -3-methyl-7- (2-butyn-1-yl) -8- (3-aminopiperidin-1) -yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.23 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 0.1) Mass spectrum (ESI⁺): m / z = 543 [M + H]⁺ (183) 1- {[4- (Pyrrolidin-1-yl) -quinazolin-2-yl] methyl} -3-methyl-7- (2-butyn-1-yl) -8- (3-aminopiperidin-1 -yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.50 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia - 90: 10: 0.1) Mass Spectrum (ESI⁺): m / z = 528 [M + H]⁺ (184) 1- [2- (3-Methyl-2-oxo-2,3-dihydro-1-7-benzoimidazol-4-yl) -2-oxo-ethyl] -3-methyl-7 (2-butyne -1-yl) -8- (3-amino-piperidin-1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.43 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass spectrum (ESI⁺): m / z = 505 [M + H]⁺ (18) 1 - [(4-Cyano-naphthalen-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-aminopiperidin-1 yl) xanthine

Rf value: 0.27 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 482 [M + H]⁺ (186) 1 - [(imidazo [1,2-a] pyridin-3-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-aminopiperidin-1-yl) xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

165

Rf value: 0.37 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 447 [M + H]⁺ (187) 1- [(8-methyl-imidazo [1,2-a] pyridin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-aminopiperidine -1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.46 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 461 [M + H]⁺ (188) 1 - [(4-amino-quinazolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidinyl) xanthine ( Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.40 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 0.1) Mass spectrum (ESI⁺): m / z = 474 [M + H]⁺ (189) 1- (2-Phenyl-2-oxo-ethyl) -3-methyl-7 - ((Z) -2-buten-1-yl) -8- (3-amino-piperidin-1-yl) xanthine

Mass Spectrum (ESI⁺): m / z = 437 [M + H]⁺ (190) 1 - [(8-methoxy-quinolin-5-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidinyl) xanthine x 2 trifluoroacetic acid

Rf value: 0.45 (silica gel, methylene chloride / methanol = 5: 1)

Mass Spectrum (ESI⁺): m / z = 488 [M + H]⁺ (191) 1 - [(5-methoxy-quinolin-8-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidinyl) xanthine x trifluoroacetic acid

Rf value: 0.20 (silica gel, ethyl acetate / methanol = 1: 1)

Mass Spectrum (ESI⁺): m / z = 488 [M + H]⁺ (192) 1 - [(4-phenyl-quinazolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidinyl) xanthine ( Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.60 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1)

166

Mass Spectrum (ESI⁺): m / z = 535 [M + H]⁺ (193) 1- [(7-methyl-imidazo [1,2-a] pyridin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-aminopiperidine -1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.48 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 461 [M + H]⁺ (194) 1 - [(2-cyclopropyl-quinazolin-4-yl) methyl] -3-methyl-7 - [(1-cyclopenten-1-yl) methyl] -8 (3-amino-piperidin-1-yl) xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.55 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 1)

Mass Spectrum (ESI⁺): m / z = 527 [M + H]⁺ (195) 1- (2-Oxo-4-phenyl-butyl) -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidin-1-yl) xanthine x trifluoroacetic acid

Mass Spectrum (ESI⁺): m / z = 463 [M + H]⁺ (196) 1- (2- {2 - [(methylaminocarbonyl) methylamino] phenyl} -2-oxo-ethyl) -3-methyl-7 - ((E) -2butene-1-yl) - 8 - (( 7- (3-Amino-piperidin-1-yl) -xanthine

Rf value: 0.52 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 0.1)

Mass Spectrum (ESI⁺): m / z = 523 [M + H]⁺ (197) 1- [2- (2-oxo-2,3-dihydro-17β-benzoimidazol-4-yl) -2-oxo-ethyl] -3-methyl-7- (2-butynl-yl) - 8- (3-Amino-piperidin-1-yl) -xanthine

Rf value: 0.40 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 491 [M + H]⁺ (198) 1 - [(3-difluoromethyl-isoquinolin-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-aminopiperidin-1-yl) -xanthine x trifluoroacetic acid

Rf value: 0.75 (silica gel, methylene chloride / methanol = 10: 1)

167

Mass Spectrum (ESI⁺): m / z = 508 [M + H]⁺ (199) 1- [2- (2,2-Difluoro-benzo [1,3] dioxol-4-yl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 ((R) -3-Amino-piperidin-1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.80 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 96: 4: 0.5) Mass Spectrum (ESI⁺): m / z = 515 [M + H]⁺ (200) 1- [(3-methyl-imidazo [1,2-a] pyridin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-aminopiperidine -1-yl) -xanthine

Rf value: 0.45 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 461 [M + H]⁺ (201) 1- [2- (2,2-difluoro-benzo [1,3] dioxol-4-yl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 ((5) -3-Amino-piperidin-1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Mass Spectrum (ESI⁺): m / z = 515 [M + H]⁺ (202) 1 - [(5-methyl-imidazo [1,2-a] pyridin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) - 8- (3-aminopiperidine - 1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.53 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 461 [M + H]⁺ (203) 1- [(6-methyl-imidazo [1,2-a] pyridin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-aminopiperidine -1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Melting point: 176.5-178 ° C

Mass Spectrum (ESI⁺): m / z = 461 [M + H]⁺ (204) 1- [(3-Benzyl-imidazo [1,2-a] pyridin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3 amino-piperidine) -1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

168

Melting point: 201-204 ° C

Mass Spectrum (ESI⁺): m / z = 537 [M + H]⁺ (205) 1 - [(4-isopropyl-quinazolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-aminopiperidin-1-yl) -xanthine ( Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.50 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 0.1) Mass spectrum (ESI⁺): m / z = 501 [M + H]⁺ (206) 1- [(2,3-dihydro-benzo [1,4] dioxin-6-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-aminopiperidine -1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.65 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 465 [M + H]⁺ (207) 1 - [(1-methyl-1H-indol-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1 yl) -xanthine hydrochloride (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.60 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 460 [M + H]⁺ (208) 1 - [(quinolin-3-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine (Done with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.50 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 0.1) Mass spectrum (ESI⁺): m / z = 458 [M + H]⁺ (209) 1- [(3-Phenyl-imidazo [1,2-a] pyridin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-aminopiperidine -1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.50 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 523 [M + H]⁺

169 (210) 1- [(1H-indol-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) xanthine hydrochloride

Rf value: 0.55 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass spectrum (ESI⁺): m / z = 446 [M + H]⁺ (211) 1- [2- (naphthalen-1-yl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.60 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia - 90: 10: 1) Mass spectrum (ESI⁺): m / z - 485 [M + H]⁺ (212) 1 - [(5-methoxy-isoquinolin-8-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-aminopiperidin-1-yl) -xanthine x trifluoroacetic acid

Rf value: 0.50 (silica gel, methylene chloride / methanol = 5: 1)

Mass Spectrum (ESI⁺): m / z = 488 [M + H]⁺ (213) 1 - {[1- (1-Cyano-1-methyl-ethyl) -isoquinolin-3-yl] methyl} -3-methyl-7- (2-butyn-1-yl) -8- ( 3 amino-piperidin-1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.25 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 1)

Mass Spectrum (ESI⁺): m / z = 525 [M + H]⁺ (214) 1- (2-Cyanoimino-2-phenyl-ethyl) -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) xanthine x trifluoroacetic acid ( E / Z mixture)

Mass Spectrum (ESI⁺): m / z = 459 [M + H]⁺ (215) 1 - [(1 H -benzoimidazol-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidinyl) xanthine x trifluoroacetic acid

Mass Spectrum (ESI⁺): m / z = 447 [M + H]⁺ (216) 1 - [(1-methyl-1 H -benzoimidazol-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-aminopiperidin-1-yl) ) xanthine

170

Mass Spectrum (ESI⁺): m / z = 461 [M + H]⁺ (217) 1 - [(4-phenyl-quinazolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((7?) - 3-aminopiperidin-1-yl) yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Mass Spectrum (ESI⁺): m / z = 535 [M + H]⁺ (218) 1 - [(2,3-dimethyl-quinoxalin-6-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-aminopiperidin-1-yl) - xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.50 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 0.1) Mass spectrum (ESI⁺): m / z = 487 [M + H]⁺ (219) 1 - [(2-methyl-17β-benzoimidazol-5-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-aminopiperidin-1-yl) xanthine

Rf value: 0.35 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 0.1) Mass Spectrum (ESI⁺): m / z - 461 [M + H]⁺ (220) 1 - [(4-phenyl-quinazolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((S) -3-aminopiperidin-1-yl xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Mass Spectrum (ESI⁺): m / z = 535 [M + H]⁺ (221) 1- [2- (Quinolin-8-yl -] - 2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidinyl) xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.48 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 486 [M + H]⁺ (222) 1 - [(3,4-Dimethyl-6,7-dihydro-5H- [2] pyridin-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 (3-amino-piperidin-1-yl) -xanthine x trifluoroacetic acid

Rf value: 0.25 (alumina, methylene chloride / methanol = 20: 1)

Mass Spectrum (ESI⁺): m / z = 476 [M + H]⁺

171 (223) 1 - [(3,4-Dimethyl-5,6,7,8-tetrahydroisoquinolin-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) 8- ( 3-amino-piperidin-1-yl) -xanthine x trifluoroacetic acid

Rf value: 0.50 (alumina, methylene chloride / methanol = 20: 1)

Mass Spectrum (ESI⁺): m / z = 490 [M + H]⁺ (224) 1- [2- (1 H -indol-4-yl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino) piperidin-yl) xanthine

Rf value: 0.52 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia - 90: 10: 1) Mass Spectrum (ESI⁺): m / z - 474 [M + H]⁺ (225) 1- [(7-Benzoimidazol-5-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidinyl) xanthine

Rf value: 0.50 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 447 [M + H]⁺ (226) 1- [(pyrazolo [1,5-a] pyridin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-aminopiperidin-1-yl) xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.47 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 447 [M + H]⁺ (227) 1 - [(1-methyl-2-oxo-1,2-dihydro-quinolin-6-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3 amino-piperidin-1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.40 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 488 [M + H]⁺ (228) 1 - [(2-Oxo-1,2-dihydro-quinolin-6-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-aminopiperidin-1 yl) xanthine

Rf value: 0.23 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass spectrum (ESI⁺): m / z = 474 [M + H]⁺

172 (229) 1 - [(2,3,8-trimethyl-quinoxalin-6-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-aminopiperidin-1-yl) xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.37 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 501 [M + H]⁺ (230) 1 - [(8-methyl-quinoxalin-6-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidinl-yl) -xanthine ( Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.35 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia - 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 473 [M + H]⁺ (231) 1 - [(4-methyl-phthalazin-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) - xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.55 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 1)

Mass Spectrum (ESI⁺): m / z = 473 [M + H]⁺ (232) 1 - [(4-bromo-3-methoxy-isoquinolin-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-aminopiperidin-1-yl) xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.40 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 1)

Mass Spectrum (ESI⁺): m / z = 566, 568 [M + H]⁺ (233) 1- (2-Phenyl-2-oxo-ethyl) -3-methyl-7 - ((E) -1-buten-1-yl) -8- (3-amino-piperidin-1-yl) xanthine

Rf value: 0.31 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 437 [M + H]⁺ (234) 1 - [(4-difluoromethoxy-naphthalen-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-aminopiperidin-1-yl ) xanthine

173

Rf value: 0.08 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 95: 5: 1) Mass Spectrum (ESI⁺): m / z = 523 [M + H]⁺ (23) 1- [2- (1H-indol-7-yl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino) -piperidin-1-yl) -xanthine x trifluoroacetic acid

Rf value: 0.46 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 474 [M + H]⁺ (236) 1 - [(E) -3 - (2-nitro-phenyl) -2-propen-1-yl] -3-methyl-7- (2-butyn-1-yl) -8- (3- aminopiperidin-1-yl) -xanthine

Mass Spectrum (ESI⁺): m / z = 478 [M + H]⁺ (237) 1- ((E) -3-Pentafluorophenyl-2-propen-1-yl) -3-methyl-7- (2-butyn-1-yl) -8- (3-aminopiperidin-1-yl) xanthine

Mass Spectrum (ESI⁺): m / z = 523 [M + H]⁺ (23 8) 1 - [(4-nitro-naphthalen-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((5) -3-amino-piperidinyl) yl) xanthine

Rf value: 0.38 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 502 [M + H]⁺ (239) 1- {[1- (2-Cyanoethyl) -1H-benzoimidazol-2-yl] methyl} -3-methyl-7- (2-butyn-1-yl) -8- (3 amino-piperidine -1-yl) -xanthine hydrochloride (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.55 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 0.1)

Mass Spectrum (ESI⁺): m / z = 500 [M + H]⁺ (240) 1- ({1 - [(methylaminocarbonyl) methyl] -1H-benzoimidazol-2-yl} methyl) -3-methyl-7- (2butyn-1-yl) -8- (3-amino-piperidin-2-yl) l-yl) -xanthine x trifluoroacetic acid Mass Spectrum (ESI⁺): m / z = 518 [M + H]⁺

174 (241) 1 - [(1-Benzyl-1H-benzoimidazol-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-aminopiperidin-1-yl) xanthine

Rf value: 0.47 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 0.1)

Mass Spectrum (ESI⁺): m / z = 537 [M + H]⁺ (242) 1 - [(benzoxazol-2-y) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) xanthine x trifluoroacetic acid

Rf value: 0.50 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 0.1)

Mass Spectrum (ESI⁺): m / z = 448 [M + H]⁺ (243) 1 - [(5-nitro-benzooksazol-2-y) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidinl-yl) -xanthine

Rf value: 0.49 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 0.1)

Mass Spectrum (ESI⁺): m / z = 493 [M + H]⁺ (244) 1 - [(3-methyl-isoquinolin-1-yl) methyl] -3-methyl-7- (3-methyl-1-buten-1-yl) -8 - ((7?) -3 amino) piperidin-1-yl) -xanthine

Rf value: 0.21 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 488 [M + H]⁺ (245) 1 - [(quinolin-7-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine (Done with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.55 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass spectrum (ESI⁺): m / z = 458 [M + H]⁺ (246) 1 - [([1,5] naphthyridin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.51 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass spectrum (ESI⁺): m / z = 459 [M + H]⁺

175 (247) 1 - [(8-methyl-quinoxalin-6-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((7?) -3-aminopiperidin-1-yl) yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.49 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass spectrum (ESI⁺): m / z = 473 [M + H]⁺ (248) 1 - [(2,3,8-trimethyl-quinoxalin-6-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((7?) - 3- aminopiperidin-1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.46 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 501 [M + H]⁺ (249) 1 - [([1,6] naphthyridin-5-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.50 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia - 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 459 [M + H]⁺ (250) 1 - [([1,8] naphthyridin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.45 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 459 [M + H]⁺ (251) 1 - [(4-fluoro-naphthalen-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidinl-yl xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.50 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 475 [M + H]⁺ (252) 1 - [([1,5] naphthyridin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((7?) - 3-amino-piperidine -lyl) xanthine

176 (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Mass Spectrum (ESI⁺): m / z = 459 [M + H]⁺ (253) 1- [2- (3-methyl-2-oxo-2,3-dihydro-benzooksazol-4-yl) -2-oxo-ethyl] -3-methyl-7- (2butyn-1-yl) -8 - ((E) -3-Amino-piperidin-1-yl) -xanthine (Done with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Melting point: 187-189 ° C

Mass Spectrum (ESI⁺): m / z = 506 [M + H]⁺ (254) 1 - [(8-phenyl-quinoxalin-6-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((7?) -3-aminopiperidin-1 - yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.50 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 535 [M + H]⁺ (255) 1 - [([1,5] naphthyridin-4-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((7?) - 3-amino-piperidine -lyl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.52 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESC): m / z = 459 [M + H]⁺ (256) 1- ((E) -3-pentafluorophenyl-allyl) -3-methyl-7- (2-butyn-1-yl) -8 - ((7?) -3-amino-piperidinyl) - xanthine

Mass Spectrum (ESC): m / z - 523 [M + H]⁺ (257) 1- [(E) -3- (2-Trifluoromethyl-phenyl) -allyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((7?) - 3-aminopiperidine -1-yl) -xanthine

Mass Spectrum (ESC): m / z = 501 [M + H]⁺ (258) 1- [(E) -3- (3-Trifluoromethyl-phenyl) -allyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((7?) -3-aminopiperidine -1-yl) -xanthine

Mass Spectrum (ESC): m / z = 501 [M + H]⁺

177 (259) 1- [(E) -3- (4-Trifluoromethyl-phenyl) -allyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((7?) -3-aminopiperidine -1-yl) -xanthine

Mass Spectrum (ESI⁺): m / z = 501 [M + H]⁺ (260) 1 - [(3-trifluoromethyl-isoquinolin-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((7?) - 3-aminopiperidin-1-yl) yl) -xanthine x trifluoroacetic acid Mass Spectrum (ESI⁺): m / z = 526 [M + H]⁺ (261) 1 - [(3-methyl-isoquinolin-1-yl) methyl] -3-isopropyl-7- (2-butyn-1-yl) -8 - ((7?) - 3-amino] piperidine-1 -yl) -xanthin (262) 1 - [(3-methyl-isoquinolin-1-yl) methyl] -3- (4-fluorophenyl) -7- (2-butyn-1-yl) -8 - (( ?) - 3-Aminopiperidin-1-yl) -xanthine (263) 1 - [(3-methyl-isoquinolin-1-yl) methyl] -3-methyl-7- (2-cyano-benzyl) -8- ( 3-Aminopiperidin-1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.51 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 1)

Mass Spectrum (ESI⁺): m / z = 535 [M + H]⁺ (264) 1 - [(3-difluoromethyl-isoquinolin-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((7?) -3-aminopiperidin-1 - yl) xanthine

Mass Spectrum (ESI⁺): m / z = 508 [M + H]⁺ (265) 1 - [(4-chloro-3-methoxy-isoquinolin-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-aminopiperidin-1-yl) xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Mass Spectrum (ESI⁺): m / z = 522, 524 [M + H]⁺

Rf value: 0.40 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 1)

178 (266) 1 - [(4-ethoxy-quinazolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) - 8- (3-amino-piperidin-1-yl) -xanthine (Made with 1 M essential hydrochloric acid)

Rf value: 0.60 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 1)

Mass Spectrum (ESI⁺): m / z = 503 [M + H]⁺ (267) 1 - [(4-isopropyloxy-quinazolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-aminopiperidin-1-yl) -xanthine ( Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.55 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 1)

Mass Spectrum (ESI⁺): m / z = 517 [M + H]⁺ (268) 1 - [(2-methyl-benzothiazol-6-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidinl-yl) -xanthine ( Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Melting point: 167 ° C

Mass Spectrum (ESI⁺): m / z = 478 [M + H]⁺ (269) 1- [(3-phenyl-isoquinolin-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((7?) -3-aminopiperidin-1 - yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.45 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 1)

Mass Spectrum (ESI⁺): m / z = 534 [M + H]⁺ (270) 1 - [(4-phenyloxy-quinazolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-aminopiperidin-1-yl) -xanthine ( Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.60 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 1)

Mass Spectrum (ESI⁺): m / z = 551 [M + H]⁺

179 (271) 1 - [(4-phenyl-quinazolin-2-yl) methyl] -3-cyclopropyl-7- (2-butyn-1-yl) -8- (3-aminopiperidin-1-yl) -xanthine ( Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.45 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 1)

Mass Spectrum (ESI⁺): m / z = 561 [M + H]⁺ (272) 1 - [(3-methyl-isoquinolin-1-yl) methyl] -3-cyclopropyl-7- (2-butyn-1-yl) -8- (3-aminopiperidin-1-yl) -xanthine ( Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.55 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 1)

Mass Spectrum (ESI⁺): m / z = 498 [M + H]⁺ (273) 1 - [(2-phenyl-quinazolin-4-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidinyl) xanthine ( Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.50 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 1)

Mass Spectrum (ESI⁺): m / z = 535 [M + H]⁺ (274) 1- [2- (2-methoxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidinl-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.29 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 465 [M + H]⁺ (275) 1- [2- (3-Methoxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidinl-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.27 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 465 [M + H]⁺

180 (276) 1- [2- (3-Trifluoromethoxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((7?) -3-amino-piperidine -1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.29 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 519 [M + H]⁺ (277) 1- [2- (biphenyl-2-yl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((7?) -3-amino -piperidinl-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.35 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 1)

Mass Spectrum (ESI⁺): m / z = 511 [M + H]⁺ (278) 1- [2- (biphenyl-3-yl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((7?) -3-amino -piperidinl-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.35 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 1)

Mass Spectrum (ESI⁺): m / z = 511 [M + H]⁺ (279) 1- [2- (3-Isopropyloxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((7?) -3-aminopiperidine -1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.20 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 493 [M + H]⁺ (280) 1 - [(3-methyl-isoquinolin-1-yl) methyl] -3-cyclopropyl-7- (2-butyn-1-yl) -8 - ((7?) - 3-aminopiperidin-1 - yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.50 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 1)

Mass Spectrum (ESI⁺): m / z = 498 [M + H]⁺

181 (281) 1 - [(4-phenyl-quinazolin-2-yl) methyl] -3-cyclopropyl-7- (2-butyn-1-yl) -8 - ((7?) - 3-aminopiperidin-1 - yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.45 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 1)

Mass Spectrum (ESI⁺): m / z = 561 [M + H]⁺ (282) 1 - [(4-cyano-naphthalen-1-yl) methyl] -3-cyclopropyl-7- (2-butyn-1-yl) -8 - ((7?) - 3-aminopiperidin-1 - yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Melting point: 191 ° C

Mass Spectrum (ESI⁺): m / z = 508 [M + H]⁺ (283) 1- [2- (2-phenyloxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-aminopiperidin-1-yl) 1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.40 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 1)

Mass Spectrum (ESI⁺): m / z = 527 [M + H]⁺ (284) 1- [2- (3-Ethoxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((7?) -3-aminopiperidine -1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.29 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 479 [M + H]⁺ (285) 1- [2- (3-methoxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((7?) -3-aminopiperidine -1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.28 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 465 [M + H]⁺

182 (286) 1- [2- (2-methoxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((7?) -3 - aminopiperidin-1-yl) xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.34 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass spectrum (ESI⁺): m / z = 465 [M + H]⁺ (287) 1 - [(3-methyl-isoquinolin-1-yl) methyl] -3-methyl-7- (2-chloro-benzyl) -8 - ((7?) -3-aminopiperidin-1-yl) xanthine

Mass Spectrum (ESI⁺): m / z - 544, 546 [M + H]⁺ (288) 1 - [(3-methyl-isoquinolin-1-yl) methyl] -3-methyl-7- (2-bromo-benzyl) -8 - ((7?) -3-aminopiperidin-1-yl) xanthine

Mass Spectrum (ESI⁺): m / z = 588, 590 [M + H]⁺ (289) 1 - [(1,2,3,4-tetrahydro-phenanthridin-6-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-aminopiperidin-1 -yl) -xanthine x trifluoroacetic acid

Rf value: 0.75 (alumina, methylene chloride / methanol - 10: 1)

Mass Spectrum (ESI⁺): m / z = 512 [M + H]⁺ (290) 1- [2- (3-difluoromethoxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((7?) -3-amino-piperidine -1-yl) -xanthine (Made with 5-6 M isopropanol-containing hydrochloric acid in methylene chloride)

Rf value: 0.28 (silica gel, methylene chloride / methanol / conc. Aqueous ammonia = 90: 10: 1) Mass Spectrum (ESI⁺): m / z = 501 [M + H]⁺ (291) 1 - [(3-methyl-isoquinolin-1-yl) methyl] -3-methyl-7- (2-ethynyl-benzyl) -8 - ((7?) - 3-aminopiperidin-1-yl) -xanthin (292) 1 - [(3-methyl-isoquinolin-1-yl) methyl] -3-phenyl-7- (2-butyn-1-yl) -8 - ((7?) -3-aminopiperidin-1-yl) 1-yl) -xanthin (293) 1 - [(phenanthren-9-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((7?) - 3-amino-1-yl) piperidin-l-yl) xanthine

183 (294) 1 - [(4-methyl-quinazolin-2-yl) methyl] -3-methyl-7- (2-chloro-benzyl) -8 - ((5) -3-aminopiperidin-1-yl) - xanthine

Rf value: 0.35 (silica gel, methylene chloride / methanol / triethylamine = 90: 10: 1)

Mass Spectrum (ESI⁺): m / z = 545, 547 [M + H]⁺ (295) 1 - [(4-phenyl-quinazolin-2-yl) methyl] -3-methyl-7- (2-chloro-benzyl) -8 - ((5) -3-aminopiperidin-1-yl) - xanthine

Rf value: 0.40 (silica gel, methylene chloride / methanol / triethylamine = 90: 10: 1)

Mass Spectrum (ESI⁺): m / z = 607, 609 [M + H]⁺

Example 3 1- [2- (3-Carboxymethoxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3 amino-piperidine-1) yl) xanthine

Prepared by saponifying 70 mg of 1- (2- {3 - [(methoxycarbonyl) methoxy] phenyl} -2-oxoethyl) -3-methyl-7- (3-methyl-2-buten-1-yl) -8 - (3-Amino-piperidin-1-yl) -xanthine with 0.10 ml of 4 M potassium hydroxide solution in a mixture of 1 ml of tetrahydrofuran and 0.5 ml of methanol at ambient temperature.

Yield: 57 mg (84% of theoretical value)

Rf value: 0.55 (ready-made reverse phase TLC plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 0.1)

Mass Spectrum (ESI⁺): m / z = 525 [M + H]⁺

The following compounds are obtained analogously to Example 3:

(1) 1- [2- (2-Carboxymethoxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidine-1-yl) 1-yl) -xanthine (Made with sodium hydroxide solution)

Mass Spectrum (EST): m / z = 523 [MH] +

184

Example 4

Coated tablets containing 75 mg of active substance tablet core contain:

active substance calcium phosphate corn starch polyvinylpyrrolidone hydroxypropylmethylcellulose magnesium stearate

75.0 mg 93.0 mg 35.5 mg 10.0 mg 15.0 mg 1.5 mg

230.0 mg

Preparation:

The active substance is mixed with calcium phosphate, corn starch, polyvinylpyrrolidone, hydroxypropylmethylcellulose and half of the stated amount of magnesium stearate. Blanks 13 mm in diameter are made in a tableting machine and these are then rubbed through a 1.5 mm mesh screen using a suitable machine and mixed with the rest of the magnesium stearate. This granulate is compressed in a tableting machine to form tablets of the desired shape.

Core weight: 230 mg matrix: 9 mm, convex

The tablet nuclei thus formed are coated with a film consisting essentially of hydroxypropyl methylcellulose. The finished film coated tablets are polished with beeswax.

Weight of coated tablet: 245 mg.

Example 5

Tablets containing 100 mg of active substance

Composition:

tablet contains:

active substance 100.0 mg lactose 80.0 mg corn starch 34.0 mg polyvinylpyrrolidone 4.0 mg

185 magnesium stearate 2.0 mg

220.0 mg

Preparation Process:

The active substance, lactose and starch are mixed together and evenly moistened with an aqueous solution of polyvinylpyrrolidone. After the moist preparations are sieved (2.0 mm mesh size) and dried in a rack-type dryer at 50 ° C, it is sieved again (1.5 mm mesh size) and the lubricant added. The finished mixture is compressed to form tablets.

Weight of tablet: 220 mg

Diameter: 10 mm, two planes, faceted on both sides and with notches on one side.

Example 6

Tablets containing 150 mg of active substance

<td colspan="2">Composition:</td>

<td>1 tablet contains:</td><td></td>

<td>active substance</td><td>150.0 mg</td>

<td>powdered lactose</td><td>89.0 mg</td>

<td>cornstarch</td><td>40.0 mg</td>

<td>colloidal silica</td><td>10.0 mg</td>

<td>polyvinylpyrrolidone</td><td>10.0 mg</td>

<td>magnesium stearate</td><td>1.0 mg 300.0 mg</td>

Preparation:

The active substance, mixed with lactose, corn starch and silica, is wetted with a 20% aqueous polyvinylpyrrolidone solution and passed through a 1.5 mm mesh screen. The granules, which are dried at 45 ° C, are passed through the same sieve again and mixed with the stated amount of magnesium stearate. Tablets are compressed by the mixture.

Weight of tablet: 300 mg matrix: 10 mm, flat

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Example 7

Hard gelatin capsules containing 150 mg of active substance

<td colspan="2">1 capsule contains:</td>

<td>active substance</td><td>150.0 mg</td>

<td>corn starch (dried)</td><td>about. 80.0 mg</td>

<td>lactose (powdered)</td><td>about. 87.0 mg</td>

<td>magnesium stearate</td><td>3.0 mg</td>

about. 420.0 mg

Preparation:

The active substance is mixed with the excipients, is passed through a sieve with a mesh size of 0.75 mm and is homogeneously mixed using a suitable apparatus. The finished mixture is packed in size 1 hard gelatin capsules.

Capsule filling: approx. 320 mg

Capsule shell: size 1 hard gelatin capsule.

Example 8

Suppositories containing 150 mg of active substance

<td colspan="2">1 suppository contains:</td>

<td>active substance</td><td>150.0 mg</td>

<td>polyethylene glycol 1500</td><td>550.0 mg</td>

<td>polyethylene glycol 6000</td><td>460.0 mg</td>

<td>polyoxyethylene sorbitan</td><td>840.0 mg 2,000.0 mg</td>

Preparation:

After the suppository mass is melted, the active substance is homogeneously distributed therein and the melt is poured into cooled molds.

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Example 9

Suspension containing 50 mg of active substance

100 ml suspension contains: active substance carboxymethyl cellulose Na salt methyl p-hydroxybenzoate propyl p-hydroxybenzoate glucose glycerol

70% sorbitol solution flavoring dest. water to

1.00 g 0.10 g 0.05 g 0.01 g 10.00 g 5.00 g 20.00 g 0.30 g 100 ml

Preparation:

The distilled water is heated to 70 ° C. Methyl and propyl p-hydroxybenzoate, together with glycerol and sodium salt of carboxymethyl cellulose, are dissolved in it with stirring. The solution is cooled to ambient temperature and the active substance added and homogeneously dispersed with stirring. After the sugar, sorbitol solution and flavors are added and dissolved, the suspension is vacuum-suctioned with stirring to remove air.

ml of suspension contains 50 mg of active substance.

Example 10

Vials containing 10 mg of active substance

Composition:

active substance 10.0 mg

0.01 N hydrochloric acid qs

double distilled water to 2.0 ml

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Preparation:

The active substance is dissolved in the required amount of 0.01 N HCl, made isotonic with common salt, sterile filtered and transferred to 2 ml ampoules.

Example 11

Vials containing 50 mg of active substance

Composition:

active substance 50.0 mg

0.01 N hydrochloric acid qs

double distilled water to 10.0 ml

Preparation:

The active substance is dissolved in the required amount of 0.01 N HCl, made isotonic with common salt, sterile filtered and transferred to 10 ml ampoules.

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