HK1081552B

HK1081552B - 8-[3-amino-piperidin-1-yl]-xanthines, the production thereof and the use of the same as medicaments

Info

Publication number: HK1081552B
Application number: HK06101985.9A
Authority: HK
Inventors: Himmelsbach Frank; Langkopf Elke; Eckhardt Matthias; Mark Michael; Maier Roland; R. H. Lotz Ralf; Tadayyon Mohammad
Original assignee: 贝林格尔英格海姆法玛两合公司
Priority date: 2002-08-21
Filing date: 2003-08-18
Publication date: 2009-11-20

Description

8- [ 3-amino-piperidin-1-yl ] -xanthines, process for their preparation and their use as pharmaceutical preparations

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

Tautomers, enantiomers, diastereomers, mixtures thereof, prodrugs and salts thereof, in particular 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 dipeptidylpeptidase-IV (DPP-IV), the production thereof, the use thereof for the prophylaxis or treatment of diseases or conditions which are associated with an increased DPP-IV activity or which can be prevented or alleviated by a reduced DPP-IV activity, in particular type I or type II diabetes, pharmaceutical compositions containing a compound of the general formula (I) or a physiologically acceptable salt thereof, and processes for the production thereof.

In the above formula I

R¹Represents a methyl group, and is represented by,

methyl substituted by dimethylaminocarbonyl, pyrrolidin-1-ylcarbonyl, piperidin-1-ylcarbonyl, tert-butylcarbonyl or cyclohexylcarbonyl,

methyl substituted by naphthyl, methylnaphthyl, methoxynaphthyl, nitronaphthyl or dimethylaminonaphthyl,

methyl substituted by 2-phenylvinyl or biphenyl,

by phenyl oxadiazolyl, 5-methyl-3-phenyl-isoxazolyl, phenylpyridyl, indolyl, benzothienyl, quinolinyl, isoquinolinyl, methylisoquinolinyl, (methoxycarbonylmethylamino) -isoquinolinyl, cinnolinyl, quinazolinyl, methylquinolinyl, 1, 2-dihydro-1-methyl-2-oxo-quinolinyl, 1, 2-dihydro-2-methyl-1-oxo-isoquinolinyl, 3, 4-dihydro-4-oxo-2, 3-diazanaphthyl, 3, 4-dihydro-3-methyl-4-oxo-2, 3-diazanaphthyl, 3, 4-dihydro-4-oxo-quinazolinyl, quinoxalinyl, 3, 4-dihydro-3-methyl-4-oxo-quinazolinyl or 2-oxo-2H-chromenyl substituted methyl,

2-methoxyethyl, 2-phenoxyethyl or 2-cyanoethyl,

phenylcarbonylmethyl or 1- (phenylcarbonyl) -ethyl,

phenylcarbonylmethyl, wherein the phenyl moiety is substituted by amino, cyanomethylamino, methylcarbonylamino, ethylcarbonylamino, isopropylcarbonylamino, methoxycarbonylamino, (ethoxycarbonylamino) -carbonylamino or 2-oxo-tetrahydroimidazol-1-yl,

Phenylcarbonylmethyl, in which the phenyl moiety is substituted by carboxyl, methoxycarbonyl, ethoxycarbonyl, aminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl or morpholin-4-ylcarbonyl,

phenylcarbonylmethyl, in which the phenyl moiety is substituted by methylthio (sulfonyl), methylsulfinyl or methylsulfonyl,

phenylcarbonylmethyl, in which the phenyl moiety is substituted by carboxymethoxy, ethoxycarbonylmethoxy, isopropoxycarbonylmethoxy, aminocarbonylmethoxy, methylaminocarbonylmethoxy, ethylaminocarbonylmethoxy, isopropylaminocarbonylmethoxy, dimethylaminocarbonylmethoxy, pyrrolidin-1-ylcarbonylmethoxy or morpholin-4-ylcarbonylmethoxy,

phenylcarbonylmethyl, in which the phenyl moiety is substituted by 1- (methoxycarbonyl) -ethoxy or 1- (aminocarbonyl) -ethoxy,

phenylcarbonylmethyl, in which the phenyl moiety is substituted by methylsulfinylmethoxy,

phenylcarbonylmethyl, in which the phenyl moiety is substituted by two methoxy groups, or

Phenylcarbonylmethyl, in which in the phenyl moiety two adjacent hydrogen atoms are replaced by-O-CH₂-O、-O-CH₂-CH₂-O or-N (CH)₃) -a CO-O group substitution,

R²represents a hydrogen atom, and is represented by,

methyl, isopropyl, 2-propen-1-yl, 2-propyn-1-yl or phenyl, or

Cyanomethyl or methoxycarbonylmethyl, and

R³represents a 2-cyanobenzyl group or a 2, 6-dicyanobenzyl group,

2-methyl-2-propen-1-yl, 2-chloro-2-propen-1-yl or 3-bromo-2-propen-1-yl,

2-buten-1-yl, 3-methyl-2-buten-1-yl or 2, 3-dimethyl-2-buten-1-yl,

2-butyn-1-yl group,

1-cyclopenten-1-ylmethyl, or

2-furyl methyl.

The carboxyl group mentioned in the above radical definitions may be replaced by a group which is convertible in vivo into a carboxyl group or by a group which is negatively charged under physiological conditions,

furthermore, the amino and imino groups mentioned in the above radical definitions may be substituted by an in vivo cleavable group. Such groups are described, for example, in WO 98/46576, and in international pharmaceutical journal of n.m. nielsen et al 39, 75-85 (1987).

A compound containing a group which can be cleaved in vivo is a prodrug of the corresponding compound in which such a group which can be cleaved in vivo has been cleaved.

By a group which can be converted in vivo to a carboxyl group is meant, for example, a hydroxymethyl group, a carboxyl group esterified with an alcohol, wherein the alcohol moiety is preferably C_1-6Alkanol, phenyl-C_1-3-alkanol, C_3-9-cycloalkanol, wherein C_5-8The cycloalkanol may additionally be substituted by one or two C _1-3Alkyl substitution, C_5-8Cycloalkanols in which the methylene group in position 3 or 4 is replaced by an oxygen atom or by an imino group, which imino group may optionally be substituted by C_1-3Alkyl, phenyl-C_1-3Alkyl, phenyl-C_1-3Alkoxycarbonyl or C_2-6Alkanoyl substituted and cycloalkanol moieties may additionally be substituted by one or two C_1-3-alkyl substitution, C_4-7-Cycloenol, C_3-5Enol, phenyl-C_3-5Enol, C_3-5-alkynols or phenyl-C_3-5Alkynols, with the proviso that no bond is present from a carbon atom having a double or triple bond to an oxygen atom, C_3-8-cycloalkyl-C_1-3Alkanols, bicyclic alkanols having a total of 8 to 10 carbon atoms, which may additionally be substituted on the bicycloalkane moiety by one or two C_1-3-alkyl-substituted, 1, 3-dihydro-3-oxo-1-isobenzofuranol or alcohol of formula

R_p-CO-O-(R_qCR_r)-OH，

Wherein

R_pIs represented by C_1-8Alkyl radical, C_5-7-cycloalkyl, C_1-8-alkoxy, C_5-7-cycloalkyloxy, phenyl or phenyl-C_1-3-an alkyl group,

R_qrepresents a hydrogen atom, C_1-3Alkyl radical, C_5-7-cycloalkyl or phenyl, and

R_rrepresents a hydrogen atom or C_1-3-an alkyl group,

the term "group having a negative charge under physiological conditions" means, for example, tetrazol-5-yl, phenylcarbonylaminocarbonyl, trifluoromethylcarbonylaminocarbonyl, C_1-6Alkylsulfonylamino, phenylsulfonylamino, benzylsulfonylamino, trifluoromethylsulfonylamino, C _1-6-alkylsulfonylaminocarbonyl, phenylsulfonylaminocarbonyl, benzylsulfonylaminocarbonyl or perfluoro-C_1-6-an alkylsulfonylaminocarbonyl group,

by a group cleavable in vivo from an imino or amino group is meant, for example, a hydroxy group, an acyl group, such as a phenylcarbonyl group, optionally substituted by a fluorine, chlorine, bromine or iodine atom, by C_1-3-alkyl or C_1-3Alkoxy mono-or di-substituted, the substituents being the same or different, pyridine acyl or C_1-16Alkanoyl such as formyl, acetyl, propionyl, butyryl, pentanoyl or hexanoyl, 3, 3, 3-trichloropropionyl or allyloxycarbonyl, C_1-16-alkylcarbonyl or C_1-16Alkylcarbonyloxy, in which the hydrogen atoms may be replaced in whole or in part by fluorine or chlorine atoms, such as methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, tert-butoxycarbonyl, pentyloxycarbonyl, hexyloxycarbonyl, octyloxycarbonyl, nonyloxycarbonyl, decyloxycarbonyl, undecyloxycarbonyl, dodecyloxycarbonyl, hexadecyloxycarbonyl, methylcarbonyloxy, ethylcarbonyloxy, 2, 2, 2-trichloroethylcarbonyloxy, propylcarbonyloxy, isopropylcarbonyloxy, butylcarbonyloxy, tert-butylcarbonyloxy, pentylcarbonyloxy, hexylcarbonyloxy, octylcarbonyloxy, nonylcarbonyloxy, decylcarbonyloxy, undecylcarbonyloxy, dodecylcarbonyloxy or hexadecylcarbonyloxy, phenyl-C-carbonyloxy _1-6Alkoxycarbonyl, such as benzyloxycarbonyl, phenylethoxycarbonyl or phenylpropoxycarbonyl, 3-aminoPropionyl, in which the amino group may be replaced by C_1-6-alkyl or C_3-7Cycloalkyl is mono-or di-substituted and the substituents may be the same or different, C_1-3-alkylsulfonyl-C_2-4-alkoxycarbonyl, C_1-3-alkoxy-C_2-4-alkoxy-C_2-4-alkoxycarbonyl, R_p-CO-O-(R_qCR_r)-O-CO、C_1-6-alkyl-CO-NH- (R)_sCR_t) -O-CO-or C_1-6-alkyl-CO-O- (R)_sCR_t)-(R_sCR_t) -O-CO-group, wherein R_pTo R_rAre as defined above in the description and are,

R_sand R_tWhich may be the same or different, represent a hydrogen atom or C_1-3-an alkyl group.

A first object of the present invention relates to compounds of the general formula (I), in which

R¹Represents a methyl group substituted by dimethylaminocarbonyl, pyrrolidin-1-ylcarbonyl, piperidin-1-ylcarbonyl, tert-butylcarbonyl or cyclohexylcarbonyl,

methyl substituted by naphthyl, methylnaphthyl, methoxynaphthyl, nitronaphthyl or (dimethylamino) -naphthyl,

methyl substituted by 2-phenylvinyl or biphenyl,

by phenyl-oxadiazolyl, 5-methyl-3-phenyl-isoxazolyl, phenyl-pyridyl, indolyl, benzothienyl, 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-2, 3-diazanaphthyl, 3, 4-dihydro-3-methyl-4-oxo-2, 3-diazanaphthyl, 3, 4-dihydro-4-oxo-quinazolinyl, indolyl, phenylquinolinyl, isoquinolinyl, methylisoquinolinyl, cinnolinyl, quinazolinyl, quinazolin, 3, 4-dihydro-3-methyl-4-oxo-quinazolinyl or 2-oxo-2H-chromenyl substituted methyl,

2-methoxyethyl, 2-phenoxyethyl or 2-cyanoethyl,

phenylcarbonylmethyl or 1- (phenylcarbonyl) -ethyl,

phenylcarbonylmethyl, in which the phenyl moiety is substituted by methylthio, methylsulfinyl or methylsulfonyl,

R²represents a methyl group, an isopropyl group or a phenyl group,

and

R³2-methyl-2-propen-1-yl, 2-chloro-2-propen-1-yl or 3-bromo-2-propen-1-yl,

2-buten-1-yl or 2, 3-dimethyl-2-buten-1-yl,

2-butyn-1-yl group,

1-cyclopenten-1-ylmethyl, or

(ii) a 2-furyl methyl group,

and the following compounds

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

1- (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,

1- (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) -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,

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

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,

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,

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

1- (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-2H-chromen-4-yl) methyl ] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine,

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

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

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

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

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,

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

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

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

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

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

1- [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- (3-amino-piperidin-1-yl) -xanthine,

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

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

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

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

1- ((E) -3-phenyl-allyl) -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine,

1- [ (benzo [ b ] thiophen-3-yl) methyl ] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine,

1- [ (1H-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,

1- (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-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine,

1- ({5- [ (methoxycarbonyl) methylamino ] -isoquinolin-1-yl } methyl) -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine,

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

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

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,

1- [2- (pyrrolidin-1-yl) -2-oxo-ethyl ] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-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-benzooxazol-7-yl) -2-oxo-ethyl ] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine,

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,

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,

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

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

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,

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,

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

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

1- (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-buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine,

1- [2- (3-methyl-2-oxo-2, 3-dihydro-benzooxazol-4-yl) -2-oxo-ethyl ] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine,

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,

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,

1- [2- (2-oxo-2, 3-dihydro-benzooxazol-7-yl) -2-oxo-ethyl ] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine,

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

1- [ (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,

tautomers, enantiomers, diastereomers, mixtures thereof, prodrugs thereof, and salts thereof.

A first preferred subgroup of the first object of the invention comprises compounds of the general formula I, in which

R¹Represents a 4-methoxy-1-naphthylmethyl group,

2-quinolylmethyl, 4-quinolylmethyl or 6-quinolylmethyl,

1-isoquinolylmethyl, 3-methyl-1-isoquinolylmethyl, 4-methyl-1-isoquinolylmethyl or 3-isoquinolylmethyl, or

2-quinazolinylmethyl, 4-methyl-2-quinazolinylmethyl, or 4-quinazolinylmethyl,

R²represents a methyl group, and

R³represents 2-buten-1-yl or 2-butyn-1-yl,

tautomers, enantiomers, diastereomers, mixtures thereof, and salts thereof.

A second preferred subgroup of the first object of the invention comprises compounds of the general formula I, in which

R¹Represents [2- (methylcarbonylamino) -phenyl]-a carbonyl group of a methyl group,

[2- (ethylcarbonylamino) -phenyl ] -carbonylmethyl, or

[2- (isopropylcarbonylamino) -phenyl ] -carbonylmethyl,

R²represents a methyl group, and

R³represents 2-buten-1-yl or 2-butyn-1-yl,

Tautomers, enantiomers, diastereomers, mixtures, and base salts thereof.

A third preferred subgroup of the first object of the invention comprises compounds of the general formula I according to claim 1, wherein

R¹Is represented by [2- (ammonia)Alkylcarbonylmethoxy) -phenyl]-a carbonyl group of a methyl group,

[2- (methylaminocarbonylmethoxy) -phenyl ] -carbonylmethyl,

[2- (ethylamino-carbonylmethoxy) -phenyl ] -carbonylmethyl, or

[2- (isopropylaminocarbonylmethoxy) -phenyl ] -carbonylmethyl,

R²represents a methyl group, and

R³represents a 2-buten-1-yl group,

2-butyn-1-yl, or

1-cyclopenten-1-ylmethyl group,

tautomers, enantiomers, diastereomers, mixtures thereof, and salts thereof.

A second object of the invention relates to compounds of the general formula I, in which

R¹Represents a methyl group substituted by a naphthyl, fluoronaphthyl, methylnaphthyl, methoxynaphthyl, (difluoromethoxy) -naphthyl, cyanonaphthyl, nitronaphthyl or (dimethylamino) -naphthyl group,

a methyl group substituted with a phenanthryl group,

methyl substituted by 2-phenylvinyl, 2- [ (trifluoromethyl) -phenyl ] -vinyl, 2- (nitrophenyl) vinyl, 2- (pentafluorophenyl) vinyl or biphenyl,

by phenyloxadiazolyl, phenylpyridyl, indolyl, methylindolyl, dimethyl-6, 7-dihydro-5H- [2] pyridyl, benzimidazolyl, methylbenzimidazolyl, (cyanoethyl) -benzimidazolyl, (methylamino-carbonyi-methyl) benzimidazolyl, benzylbenzimidazolyl, benzofuranyl, acetylbenzofuranyl, cyanobenzofuranyl, benzoxazolyl, nitrobenzoxazolyl, benzothienyl, methylbenzothiazolyl, quinolinyl, methoxyquinolinyl, isoquinolinyl, methylisoquinolinyl, (difluoromethyl) -isoquinolinyl, (trifluoromethyl) -isoquinolinyl, dimethylisoquinolinyl, (1-cyano-1-methylethyl) isoquinolinyl, phenylisoquinolinyl, methoxyisoquinolinyl, quinonyl, quino, Methoxy-chloro-isoquinolinyl, methoxy-bromo-isoquinolinyl, (methoxycarbonylmethylamino) -isoquinolinyl, dimethyl-5, 6, 7, 8-tetrahydroisoquinolinyl, 1, 2, 3, 4-tetrahydrophenanthridinyl, cinnolinyl, quinazolinyl, methylquinazolinyl, isopropylquinazolinyl, cyclopropylquinazolinyl, phenylquinazolinyl, aminoquinazolinyl, (dimethylamino) -quinazolinyl, pyrrolidin-1-ylquinazolinyl, piperidin-1-ylquinazolinyl, piperazin-1-ylquinazolinyl, morpholin-4-ylquinazolinyl, ethoxyquinazolinyl, isopropyloxyquinazolinyl, phenyl-oxyquinazolinyl, imidazo [1, 2-a ] pyridinyl, methylimidazo [1, 2-a ] pyridyl, phenyl-imidazo [1, 2-a ] pyridyl, benzylimidazo [1, 2-a ] pyridyl, pyrazolo [1, 5-a ] pyridyl, quinoxalinyl, methylquinoxalinyl, dimethylquinoxalinyl, trimethylquinoxalinyl, phenylquinoxalinyl, methyl-2, 3-naphthyridinyl, 1, 5-naphthyridinyl, 2, 3-dihydro-benzo [1, 4] -dioxinyl, 1, 2-dihydro-2-oxo-quinolyl, 1, 2-dihydro-1-methyl-2-oxo-quinolyl, 1, 2-dihydro-2-methyl-1-oxo-isoquinolyl, 3, 4-dihydro-4-oxo-2, 3-naphthyridinyl, 3, 4-dihydro-3-methyl-4-oxo-2, 3-naphthyridinyl, 3, 4-dihydro-4-oxo-quinazolinyl, 3, 4-dihydro-3-methyl-4-oxo-quinazolinyl or 2-oxo-2H-chromenyl substituted methyl,

A phenyl-carbonyl-methyl group,

phenylcarbonylmethyl, in which the phenyl moiety is substituted by amino, cyanomethylamino, (ethoxycarbonylmethyl) amino, (methylaminocarbonyl) methylamino, methylcarbonylamino, ethylcarbonylamino, isopropylcarbonylamino, phenylcarbonylamino, methoxycarbonylamino, (ethoxycarbonylamino) -carbonylamino or 2-oxoimidazolidin-1-yl,

phenylcarbonylmethyl, wherein the phenyl moiety is substituted by phenyl,

phenylcarbonylmethyl, in which the phenyl moiety is substituted by methoxy, difluoromethoxy, trifluoromethoxy, ethoxy, isopropyloxy or phenyloxy,

phenylcarbonylmethyl, in which the phenyl moiety is substituted by methylsulfinylmethoxy, carboxymethoxy, ethoxycarbonylmethoxy, isopropoxycarbonylmethoxy, aminocarbonylmethoxy, methylaminocarbonylmethoxy, ethylaminocarbonylmethoxy, isopropylamino-carbonylmethoxy, dimethylaminocarbonylmethoxy, pyrrolidin-1-ylcarbonylmethoxy or morpholin-4-ylcarbonylmethoxy,

Phenylcarbonylmethyl, in which the phenyl moiety is substituted by 1- (ethoxycarbonyl) -1-methyl-ethoxy, 1- (methoxycarbonyl) -ethoxy or 1- (aminocarbonyl) -ethoxy,

phenylcarbonylmethyl, in which the phenyl moiety is substituted by two methoxy groups,

phenylcarbonylmethyl, in which the phenyl moiety is substituted by methoxy and nitro,

phenylcarbonylmethyl, in which the phenyl moiety is substituted by methoxy and amino,

phenylcarbonylmethyl, in which in the phenyl moiety two adjacent hydrogen atoms are replaced by-O-CH₂-O、-O-CF₂-O、-O-CH₂-CH₂-O、-NH-CO-NH、-N(CH₃)-CO-NH、-N(CH₃)-CO-N(CH₃) -NH-CO-O-or-N (CH)₃) -a CO-O group substitution,

(2-phenylethyl) carbonylmethyl group,

naphthylcarbonylmethyl, indolylcarbonylmethyl or quinolinylcarbonylmethyl, or 2-cyanoimino-2-phenyl-ethyl,

R²represents methyl, isopropyl, cyclopropyl, phenyl or fluorophenyl, and

R³represents 2-methyl-2-propen-1-yl, 2-chloro-2-propen-1-yl or 3-bromo-2-propen-1-yl,

1-buten-1-yl, 3-methyl-1-buten-1-yl, 2-methyl-2-buten-1-yl or 2, 3-dimethyl-2-buten-1-yl,

2-butyn-1-yl group,

1-cyclopenten-1-ylmethyl, or

(ii) a 2-furyl methyl group,

tautomers, enantiomers, diastereomers, mixtures, prodrugs, and salts thereof.

A preferred subgroup of the second object of the invention comprises compounds of the general formula I, in which

R¹And R²Are as defined above, and

R³represents 1-buten-1-yl, 2-buten-1-yl or 2-butyn-1-yl,

tautomers, enantiomers, diastereomers, mixtures thereof, and salts thereof.

A particularly preferred subgroup of the second object of the invention comprises compounds of the general formula I, wherein R¹Represents a methyl group substituted by a naphthyl, fluoronaphthyl, methylnaphthyl, methoxynaphthyl, (difluoromethoxy) -naphthyl, cyanonaphthyl or nitronaphthyl group,

methyl substituted by 2- (pentafluorophenyl) ethenyl,

by benzofuranyl, methylbenzothiazolyl, quinolinyl, methoxyquinolinyl, isoquinolinyl, methylisoquinolinyl, (difluoromethyl) -isoquinolinyl, (trifluoromethyl) -isoquinolinyl, dimethylisoquinolinyl, (1-cyano-1-methyl-ethyl) isoquinolinyl, phenyl-isoquinolinyl, methoxyisoquinolinyl, 1, 2, 3, 4-tetrahydrophenanthridinyl, quinazolinyl, methylquinazolinyl, isopropylquinazolinyl, cyclopropylquinazolinyl, phenylquinazolinyl, aminoquinazolinyl, (dimethylamino) -quinazolinyl, pyrrolidin-1-ylquinazolinyl, piperidin-1-ylquinazolinyl, piperazin-1-ylquinazolinyl, morpholin-4-ylquinazolinyl, ethoxyquinazolinyl, and ethoxyquinazolinyl, Isopropyloxyquinazolinyl, quinoxalinyl, methylquinoxalinyl, dimethylquinoxalinyl, trimethylquinoxalinyl, phenylquinoxalinyl, [1, 5] naphthyridinyl, [1, 6] naphthyridinyl, [1, 8] naphthyridinyl or 1, 2-dihydro-1-methyl-2-oxo-quinolinyl-substituted methyl,

A phenyl-carbonyl-methyl group,

phenylcarbonylmethyl, wherein the phenyl moiety is substituted by phenyl,

phenylcarbonylmethyl, in which in the phenyl moiety two adjacent hydrogen atoms are replaced by-O-CH₂-O、-O-CF₂-O、-O-CH₂-CH₂-O、-N(CH₃)-CO-N(CH₃) or-N (CH)₃) -a CO-O group substitution,

R²represents methyl, isopropyl, cyclopropyl, phenyl or 4-fluorophenyl, and

R³represents 1-buten-1-yl, 2-buten-1-yl or 2-butyn-1-yl,

tautomers, enantiomers, diastereomers, mixtures thereof, and salts thereof.

A second preferred subgroup of the second object of the invention comprises compounds of the general formula I, wherein R¹And R²Is as defined directly above, and R³Represents 1-buten-1-yl, tautomers, enantiomers, diastereomers, mixtures and salts thereof.

A third preferred subgroup of the second object of the invention comprises compounds of the general formula I, wherein R¹And R²Is as defined directly above, and R³Represents 2-buten-1-yl, tautomers, enantiomers, diastereomers, mixtures and salts thereof.

A fourth preferred subgroup of the second object of the invention comprises compounds of the general formula I, wherein R¹And R²Is as defined directly above, and R³Represents but-2-yn-1-yl, tautomers, enantiomers, diastereomers, mixtures and salts thereof.

A third object of the present invention relates to compounds of the general formula I, wherein

R¹Represents a methyl group substituted by a naphthyl, fluoronaphthyl, methylnaphthyl, methoxynaphthyl, (difluoromethoxy) -naphthyl, cyanonaphthyl or nitronaphthyl group,

methyl substituted by 2- (pentafluorophenyl) ethenyl, or

By benzofuranyl, methylbenzothiazolyl, quinolinyl, methoxyquinolinyl, isoquinolinyl, methylisoquinolinyl, (difluoromethyl) -isoquinolinyl, (trifluoromethyl) -isoquinolinyl, dimethylisoquinolinyl, (1-cyano-1-methyl-ethyl) isoquinolinyl, phenyl-isoquinolinyl, methoxyisoquinolinyl, 1, 2, 3, 4-tetrahydrophenanthridinyl, quinazolinyl, methylquinazolinyl, isopropylquinazolinyl, cyclopropyl-quinazolinyl, phenylquinazolinyl, aminoquinazolinyl, (dimethylamino) -quinazolinyl, pyrrolidin-1-ylquinazolinyl, piperidin-1-ylquinazolinyl, piperazin-1-ylquinazolinyl, morpholin-4-ylquinazolinyl, ethoxyquinazolinyl, and ethoxyquinazolinyl, Isopropyloxyquinazolinyl, quinoxalinyl, methylquinoxalinyl, dimethylquinoxalinyl, trimethylquinoxalinyl, phenylquinoxalinyl, [1, 5] naphthyridinyl, [1, 6] naphthyridinyl, [1, 8] naphthyridinyl or 1, 2-dihydro-1-methyl-2-oxo-quinolinyl-substituted methyl,

R²Represents methyl, isopropyl, cyclopropyl or phenyl, and

R³represents 2-chlorobenzyl, 2-bromobenzyl, 2-ethynylbenzyl or 2-cyanobenzyl, the tautomers, the enantiomers, the diastereomers, the mixtures and the salts thereof.

A first preferred subgroup of the third object of the invention comprises compounds of the general formula I, in which

R¹Represents (3-methyl-isoquinolin-1-yl) methyl,

R²represents a methyl group, and

R³represents 2-chlorobenzyl, 2-bromobenzyl, 2-ethynylbenzyl or 2-cyanobenzyl,

tautomers, enantiomers, diastereomers, mixtures thereof, and salts thereof.

A second preferred subgroup of the third object of the invention comprises compounds of the general formula I, wherein R¹And R²Are as defined above, and R³Represents 2-chlorobenzyl, tautomers, enantiomers, diastereomers, mixtures and salts thereof.

A third preferred subgroup of the third object of the invention comprises compounds of the general formula I, wherein R¹And R²Are as defined above, and R³Represents 2-bromobenzyl, the tautomers, the enantiomers, the diastereomers, the mixtures and the salts thereof.

A fourth preferred subgroup of the third object of the invention comprises compounds of the general formula I, wherein R¹And R²Are as defined above, and R ³Represents 2-ethynylbenzyl, its tautomers, enantiomers, diastereomers, mixtures and salts thereof.

First aspect of the inventionA fifth preferred subgroup of the three objects comprises compounds of the general formula I, wherein R¹And R²Are as defined above, and R³Represents 2-cyanobenzyl, tautomers, enantiomers, diastereomers, mixtures thereof and salts thereof.

Particular preference is given to the following compounds of the general formula I:

(1)1- [ (quinazolin-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine,

(2)1- (2- {2- [ (ethylamino-carbonyl) methoxy ] -phenyl } -2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine,

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

(4)1- (2-phenyl-2-oxo-ethyl) -3-methyl-7- ((E) -2-buten-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine,

(5)1- [ (3-methyl-isoquinolin-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((S) -3-amino-piperidin-1-yl) -xanthine,

(6)1- [ (3-methyl-isoquinolin-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine,

(7)1- [ (4-methyl-isoquinolin-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((S) -3-amino-piperidin-1-yl) -xanthine,

(8)1- [ (4-methyl-isoquinolin-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine,

(9)1- [2- (2, 3-dihydro-benzo [1, 4] dioxine (dioxine) -5-yl) -2-oxo-ethyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3- (R) -amino-piperidin-1-yl) -xanthine,

(10)1- [ (4-methoxy-naphthalen-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((S) -3-amino-piperidin-1-yl) -xanthine,

(11)1- [ (4-methoxy-naphthalen-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((R) -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- ((R) -3-amino-piperidin-1-yl) -xanthine,

(13)1- [ (4-methyl-quinazolin-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3- (R) -amino-piperidin-1-yl) -xanthine,

(14)1- (2- {2- [ (isopropylcarbonyl) amino ] -phenyl } -2-oxo-ethyl) -3-methyl-7- ((E) -2-buten-1-yl) -8- ((S) -3-amino-piperidin-1-yl) -xanthine,

(15)1- (2- {2- [ (methylaminocarbonyl) methoxy ] -phenyl } -2-oxo-ethyl) -3-methyl-7- ((E) -2-buten-1-yl) -8- ((R) -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) -8- ((R) -3-amino-piperidin-1-yl) -xanthine,

(18)1- (2- {2- [ (isopropylcarbonyl) amino ] -phenyl } -2-oxo-ethyl) -3-methyl-7- ((E) -2-buten-1-yl) -8- ((R) -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-piperidin-1-yl) -xanthine,

(20)1- [ (4-phenyl-quinazolin-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine,

(21)1- [ (8-methyl-quinoxalin-6-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine,

(22)1- [ (4-fluoro-naphthalen-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine,

(23)1- ((E) -3-pentafluorophenyl-allyl) -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine,

(24)1- [ (3-trifluoromethyl-isoquinolin-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine,

(25)1- [ (3-difluoromethyl-isoquinolin-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine,

(26)1- [2- (biphenyl-2-yl) -2-oxo-ethyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine,

(27)1- [ (3-methyl-isoquinolin-1-yl) methyl ] -3-cyclopropyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine,

(28)1- [2- (3-methoxy-phenyl) -2-oxo-ethyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine,

(29)1- [ (3-methyl-isoquinolin-1-yl) methyl ] -3-methyl-7- (2-chloro-benzyl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine, and

(30)1- [ (3-methyl-isoquinolin-1-yl) methyl ] -3-methyl-7- (2-bromo-benzyl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine

And tautomers, enantiomers, diastereomers, mixtures and salts thereof.

According to the invention, the compounds of the general formula I are obtained in a manner known per se, for example as follows:

a) reacting a compound of formula (II) with 3-aminopiperidine, an enantiomer thereof or a salt thereof,

in the formula (II)

R¹To R³Are as defined above, and

Z¹represents a leaving group such as a halogen atom, a substituted hydroxyl, mercapto, sulfinyl, sulfonyl or sulfonyloxy group, such as a chlorine or bromine atom, a methanesulfonyl or methanesulfonyloxy group.

The reaction is preferably carried out in a solvent, such as isopropanol, butanol, tetrahydrofuran, dioxane, dimethylformamide, dimethyl sulfoxide, ethylene glycol monomethyl ether, ethylene glycol diethyl ether or sulfolane, optionally in the presence of an inorganic or tertiary organic base, such as sodium carbonate, potassium carbonate or potassium hydroxide, a tertiary organic base, such as triethylamine, or in the presence of N-ethyl-diisopropylamine (Hunig's base), although these organic bases may also serve as solvents simultaneously, and optionally in the presence of a reaction accelerator, such as an alkali metal halide or palladium-based catalyst, at a temperature between-20 and 180 ℃, preferably between-10 and 120 ℃. However, the reaction can also be carried out without solvent or in an excess of 3-aminopiperidine.

b) Deprotection of the compound of formula (III)

Wherein R is¹、R²And R³Are as defined above.

The tert-butoxycarbonyl group is preferably cleaved by treatment with an acid, such as trifluoroacetic acid or hydrochloric acid, or with bromotrimethylsilane or iodotrimethylsilane, optionally using a solvent, such as dichloromethane, ethyl acetate, dioxane, methanol, isopropanol or diethyl ether, at a temperature between 0 and 80 ℃.

c) For the preparation of compounds of the general formula I, in which R ¹According to the definition provided hereinbefore, a compound containing a carboxyl group:

deprotection of the compound of formula (IV)

Wherein R is²And R³Are as defined above, and R¹' containing quilt C_1-4-alkyl protected carboxy.

The protecting group is cleaved by hydrolysis, for example using an acid, such as hydrochloric acid 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 hereinbefore, any reactive groups present, such as carboxyl, amino, alkylamino or imino, can be protected during the reaction by customary protecting groups, which are cleaved again after the reaction.

For example, the protecting group for carboxyl group may be trimethylsilyl, methyl, ethyl, t-butyl, benzyl or tetrahydropyranyl, and

the protecting group for amino, alkylamino or imino can be formyl, acetyl, trifluoroacetyl, ethoxycarbonyl, tert-butoxycarbonyl, benzyloxycarbonyl, benzyl, methoxybenzyl or 2, 4-dimethoxybenzyl, and further, phthaloyl can be used for the amino.

Any protecting groups used are optionally subsequently cleaved, for example by hydrolysis in an aqueous solvent, for example 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, in the presence of water, isopropanol/water, acetic acid/water, tetrahydrofuran/water or dioxane/water, or in an aprotic manner, for example in the presence of iodotrimethylsilane, at a temperature between 0 and 120 ℃, preferably between 10 and 100 ℃.

However, the cleavage of benzyl, methoxybenzyl or benzyloxycarbonyl is, for example, such as by hydrogenolysis, for example in the presence of a catalyst, such as palladium on charcoal, in a suitable solvent, such as methanol, ethanol, ethyl acetate or glacial acetic acid, optionally with addition of an acid, such as hydrochloric acid, at a temperature of between 0 and 100 ℃, preferably at a temperature of between 20 and 60 ℃ and under a hydrogen pressure of 1 to 7 bar, preferably 3 to 5 bar. However, the cleavage of the 2, 4-dimethoxybenzyl group is preferably carried out in trifluoroacetic acid in the presence of toluyl ether.

Cleavage of the tert-butyl or tert-butoxycarbonyl group is preferably carried out by treatment with an acid, such as trifluoroacetic acid or hydrochloric acid, or by treatment with iodotrimethylsilane, optionally using a solvent, such as dichloromethane, dioxane, methanol or diethyl ether.

The cleavage of the trifluoroacetyl group is preferably carried out by treatment with an acid, such as hydrochloric acid, optionally in the presence of a solvent, such as acetic acid, at a temperature between 50 and 120 ℃ or by treatment with a sodium hydroxide solution, optionally in the presence of a solvent, such as tetrahydrofuran, at a temperature between 0 and 50 ℃.

The cleavage of phthaloyl groups is preferably carried out 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 a temperature of between 20 and 50 ℃.

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

Thus, for example, the resulting cis/trans mixture can be resolved chromatographically into its cis and trans isomers, the resulting compounds of the formula I which are present as racemates can be separated into their optical enantiomers by methods known per se (cf. Allinger N.L. and Eliel E.L "general theory of stereochemistry", Vol. 6, Wiley Interscience, 1971), and the compounds of the formula I having at least 2 asymmetric carbon atoms can be resolved into their diastereoisomers on the basis of their physico-chemical differences using methods known per se, for example by chromatography and/or fractional crystallization, and if these compounds are obtained in racemic form, they can subsequently be resolved into their enantiomers as described above.

The enantiomers are preferably separated by column separation on a chiral phase, or by recrystallization from optically active solvents, or by optically active substances which are capable of reacting with racemic compounds, in particular the acids thereof, with salts or derivatives formed from activated derivatives or alcohols, for example esters or amides, and separating the diastereomeric mixtures of the salts or derivatives thus obtained, for example on the basis of their solubility differences, while the free enantiomers can be liberated from the pure diastereomeric salts or derivatives by the action of suitable reagents. Optically active acids which are generally used are, for example, the D-and L-forms of tartaric or dibenzoyltartaric acid, di-o-tolyltartaric acid, malic acid, mandelic acid, camphorsulfonic acid, glutamic acid, aspartic acid or quinic acid. Examples of the optically active alcohol include (+) -or (-) - The alcohol and the optically active acyl group in the amide may be, for example, (+) -or (-) -An oxycarbonyl group.

Furthermore, the resulting compounds of the formula I can be converted into their salts, in particular in pharmaceutical applications, into physiologically acceptable salts with inorganic or organic acids. Acids which may be used include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, methanesulfonic acid, phosphoric acid, fumaric acid, succinic acid, lactic acid, citric acid, tartaric acid or maleic acid.

Furthermore, if the novel compounds of the formula I thus obtained contain a carboxyl group, they can then, if desired, be converted into their salts with inorganic or organic bases, in particular for pharmaceutical applications, into their physiologically acceptable salts. As suitable bases, for example, sodium hydroxide, potassium hydroxide, arginine, cyclohexylamine, ethanolamine, diethanolamine and triethanolamine may be included.

The compounds of the formulae II to IV used as starting materials are known from the literature or are obtainable by methods known from the literature (cf. examples I to LXXI).

As already mentioned above, the compounds of the general formula I according to the invention and their physiologically acceptable salts have valuable pharmacological properties, in particular an inhibitory effect on the enzyme DPP-IV.

The biological properties of these novel compounds were studied as follows:

the ability of these substances and their corresponding salts to inhibit DPP-IV activity can be demonstrated in a test configuration in which an extract of the human colon cancer cell line Caco-2 is used as a source of DPP-IV. To induce DPP-IV expression, differentiation of the cells was carried out as described by Reiher et al in titled "increased expression of the intestinal cell line Caco-2", Proc. Natl. Acad. Sci. Vol.90, pp.5757-5761 (1993). The cell extracts were obtained by centrifugation at 35,000g for 30 minutes (to remove cell debris) at 4 ℃ and dissolving them in a buffer (10mM Tris HCl, 0.15M NaCl, 0.04t.i.u. aprotinin, 0.5% Nonidet-P40, pH 8.0).

The DPP-IV assay is performed as follows:

50 microliters of the matrix solution (AFC; AFC is amido-4-trifluoromethylcoumarin) at a final concentration of 100 μm was placed in a black microtiter plate. Mu.l of assay buffer (final concentration 50mM Tris-HCl, pH7.8, 50mM NaCl, 1% DMSO) was pipetted. The reaction was started by adding 30 microliters of solubilized Caco-2 protein (final concentration of 0.14 micrograms of protein per well). Usually, the test substance to be investigated is added after pre-dilution in 20. mu.l of detection buffer, wherein the volume of the detection buffer is correspondingly reduced. The reaction was carried out at ambient temperature and incubated for 60 minutes. However, the device is not suitable for use in a kitchen Thereafter, fluorescence was measured in a Victor 1420 Multilabel counter with an excitation wavelength of 405 nm and an emission wavelength of 535 nm. Blank readings (corresponding to 0% activity) were obtained in the mixture without any Caco-2 protein (volume displaced by assay buffer) and control values (corresponding to 100% activity) were obtained in the mixture without added material. The potency of the test substance in question, as IC₅₀The values are expressed, calculated from the dose/activity curve, which in each case contains 11 measurement points. The following results were obtained:

compound (example No.)	DPP-IV inhibition IC[nM]
compound (example No.)	DPP-IV inhibition IC[nM]	2(3)2(9)2(12)2(17)2(20)2(25)2(27)2(35)2(37)2(43)2(51)2(52)2(59)2(66)	2160264163212495566925022

2(80)2(86)2(96)2(99)2(100)2(108)2(129)2(130)2(131)2(132)2(135)2(137)2(138)2(139)2(142)2(145)2(148)2(150)2(151)2(152)2(185)2(217)2(247)2(251)2(256)2(260)2(264)2(277)2(280)2(285)2(287)

12213333313138414113434212813665311

2(288)

14

The compounds prepared according to the invention are well compatible, since for example no change in animal behaviour was detected when 10 mg/kg of the compound of example 2(80) was orally administered to rats.

In view of their ability to inhibit DPP-IV activity, the compounds of general formula I according to the invention, and the corresponding pharmaceutically acceptable salts thereof, are suitable for the treatment of all symptoms or conditions which can be affected by the inhibition of DPP-IV activity. Thus, it is expected that the compounds according to the invention will be suitable for the prevention or treatment of diseases or conditions such as type 1 and type 2 diabetes, diabetic complications (such as retinopathy, nephropathy or neuropathy), metabolic acidosis or ketosis, reactive hypoglycemia, insulin resistance, metabolic syndrome, lipodystrophy of different origins, arthritis, atherosclerosis and related diseases, obesity, allograft transplantation and osteoporosis caused by calcitonin. Furthermore, these substances are also suitable for preventing B-cell degeneration, such as apoptosis or necrosis of pancreatic B-cells. The substance is also suitable for improving or restoring pancreatic cell function, as well as increasing pancreatic B-cell number and size. Furthermore, and based on the effects of glucagon-like peptides such as GLP-1 and GLP-2 and their association with DPP-IV inhibition, the compounds according to the invention are equally suitable for achieving additional sedative or anxiolytic effects and also favorably influencing the catabolic state after surgery or hormonal stress response, or reducing mortality or morbidity after myocardial infarction. It is also suitable for the treatment of all the conditions associated with the above mentioned effects and mediated by GLP-1 or GLP-2. The compounds according to the invention can also be used as diuretics or antihypertensive agents and are suitable for the prophylaxis and treatment of acute renal failure. Furthermore, the compounds according to the invention are useful for the treatment of inflammatory diseases of the respiratory tract. It is likewise suitable for the prophylaxis and treatment of chronic inflammatory bowel diseases, such as Irritable Bowel Syndrome (IBS), Crohn's disease or ulcerative colitis, and pancreatitis. Likewise, it can be used for all kinds of injuries or lesions of the gastrointestinal tract, such as colitis and enteritis. It is also contemplated that DPP-IV inhibitors and thus the compounds according to the invention, may also be useful in the treatment of infertility or to improve fertility in humans or mammals, especially when infertility is associated with insulin resistance or polycystic ovary syndrome. On the other hand, these substances are suitable for influencing the motility of spermatozoa and can therefore be used as male contraceptives. In addition the substance is also suitable for treating growth hormone deficiency associated with dwarfism and is also advantageously used for any condition in which growth hormone is available. The compounds according to the invention are also suitable for the treatment of various autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis, thyroidisis (thyreodiiden) and Barcelia disease, on the basis of their inhibitory effect on DPP-IV. They can also be used for the treatment of viral diseases and, for example, in HIV infection, stimulation of blood production, in benign prostatic hyperplasia, gingivitis, and in the treatment of neuronal defects and neurodegenerative diseases such as Alzheimer's disease. The compounds are also useful in the treatment of tumors, particularly in altering tumor invasion and metastasis; examples here are their use in the treatment of T-cell lymphoma, acute lymphocytic lymphoma leukemia, cell-based thyroid cancer, basal cell carcinoma or breast cancer. Other indications are stroke, myocardial ischemia of various origins, parkinson's disease and migraine. In addition, other indications include folliculitis and epidermal hyperkeratosis, increased keratinocyte proliferation, psoriasis, encephalomyelitis, glomerulonephritis, lipodystrophy, and psychosomatic, depressive, and neuropsychiatric diseases of all different origins.

The compounds according to the invention can also be used in combination with other active substances. Therapeutic agents suitable for such combinations include, for example, antidiabetic agents such as metformin (metformin); sulfonylureas (e.g., glibenclamide (glibenclamide), tolbutamide, glimepiride (glimepiride)), nateglinide (nateglinide), repaglinide (repaglinide), thiazolidinediones (e.g., rosiglitazone (rosiglitazone), pioglitazone (pioglitazone)), PPAR-gamma agonists (e.g., GI262570) and antagonists, PPAR-gamma/alpha modulators (e.g., KRP 297), alpha-glucosidase inhibitors (e.g., acarbose (acarbose), voglibose (voglibose)), other DPPIV inhibitors, alpha 2 antagonists, insulin and insulin analogs, GLP-1 and GLP-1 analogs (e.g., Exendin-4), or dextrins. Furthermore, SGLT2 inhibitors, such as T-1095, inhibitors of protein tyrosine phosphatase 1, affect the liverSubstances which respond to deregulated glucose production, such as glucose-6-phosphatase or fructose-1, 6-bisphosphatase, inhibitors of glycogen phosphorylase, glucagon receptor antagonists and inhibitors of phosphoenolpyruvate carboxykinase, glycogen synthase kinase or pyruvate dehydrogenase, lipid lowering agents, such as HMG-CoA-reductase inhibitors (e.g.simvastatin (simvastatin), atorvastatin (atorvastatin)), fibrates (e.g.bezafibrate (bezafibrate), benzoyl lipid lowering propyl ester (fenofibrate)), nicotinic acid and derivatives thereof, PPAR-alpha agonists, PPAR-delta agonists, ACAT inhibitors (e.g.avasimibe (avastine)), or cholesterol absorption inhibitors (e.g.ezetimibe (ezetimibe)), bile acid binding substances, e.g.cholestyramine (cholestyramine), inhibitors of ileal bile acid delivery, HDL-raising compounds, for example inhibitors of CETP or modulators of ABC1, or active substances for the treatment of obesity, such as sibutramine (sibutramine) or Ribostatin (Tetrabydrolipstatin), dexfenfluramine (dexfenfluramine), yoxoline (Axoline), antagonists of the cannabinoid 1 receptor, antagonists of the MCH-1 receptor, agonists of the MC4 receptor, antagonists of NPY5 or NPY2, or beta-agonists ₃Agonists, such as SB-418790 or AD-9677, and agonists of the 5HT2c receptor.

The compounds may also be combined with drugs for the treatment of hypertension, such as with all antagonists or ACE inhibitors, diuretics, beta-blockers, Ca-antagonists, and the like, or combinations thereof.

The dosages required to achieve this effect are preferably from 1 to 100 mg, preferably from 1 to 30 mg, by intravenous administration and from 1 to 1000 mg, preferably from 1 to 100 mg, by oral administration, in each case from 1 to 4 times a day. The compounds of formula I prepared according to the invention, optionally in combination with other active substances, can be incorporated in conventional galenic preparations, such as tablets or coated tablets, capsules, powders, suspensions or suppositories, with one or more inert customary carriers and/or diluents, for example with corn starch, lactose, glucose, microcrystalline cellulose, magnesium stearate, polyvinylpyrrolidone, citric acid, tartaric acid, water/ethanol, water/glycerol, water/sorbitol, water/polyethylene glycol, propylene glycol, cetostearyl alcohol, carboxymethyl cellulose or fatty substances, such as hard fats or suitable mixtures thereof.

The following examples are intended to illustrate the invention:

Preparation of the starting compound:

example I

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

A mixture of 555 mg of 8-bromotheophylline and 0.39 ml of Hunig's base in 9 ml of N, N-dimethylformamide was combined with 600 mg of 2-bromomethyl-isophthalonitrile and stirred at ambient temperature overnight. For work-up, the reaction mixture was poured into water. The precipitate which separated out was filtered off with suction, washed with water and dried.

Yield: 686 mg (83% of theory)

R_fThe value: 0.56 (silica gel, dichloromethane/methanol ═ 95:5)

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

The following compounds are obtained in a similar manner to example I:

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

Mass spectrometry (ESI)⁺)：m/z＝269，271[M+H]⁺

(2) 3-methyl-7- (2-cyano-benzyl) -8-chloro-xanthine

Mass spectrometry (ESI)⁺)：m/z＝361，318[M+H]⁺

(3)1- (2-phenyl-2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8-bromo-xanthine

Mass spectrometry (ESI)⁺)：m/z＝415，417[M+H]⁺

(4) 3-methyl-7- [ (2-trimethylsilyl-ethoxy) methyl ] -8-bromo-xanthine

(in the presence of potassium carbonate)

Mass spectrometry (ESI)⁺)：m/z＝375，377[M+H]⁺

(5) 3-methyl-7- (3-methyl-2-buten-1-yl) -8-bromo-xanthine

Mass spectrometry (ESI)⁺)：m/z＝313，315[M+H]⁺

(6) 3-methyl-7- (2, 3-dimethyl-2-buten-1-yl) -8-bromo-xanthine

R_fThe value: 0.43 (silica gel, dichloromethane/methanol ═ 9:1)

Mass spectrometry (ESI)⁺)：m/z＝327，329[M+H]⁺

(7) 3-methyl-7- (2-butyn-1-yl) -8-bromo-xanthine

R_fThe value: 0.72 (silica gel, ethyl acetate)

Mass spectrometry (ESI)⁺)：m/z＝297/299[M+H]⁺

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

(product contaminated with about 10-20% of Z compound)

R_fThe value: 0.55 (silica gel, cyclohexane/ethyl acetate/methanol ═ 6:3:1)

Mass spectrometry (ESI)⁺)：m/z＝299，301[M+H]⁺

(9) 3-methyl-7- [ (1-cyclopenten-1-yl) methyl ] -8-bromo-xanthine

Mass spectrometry (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 spectrometry (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 (product containing about 25% of the Z isomer)

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

(12)1- (2-phenyl-2-oxo-ethyl) -3-methyl-7- (2-methyl-allyl) -8-bromo-xanthine

R_fThe value: 0.71 (silica gel, dichloromethane/methanol ═ 95:5)

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

(13)1- (2-phenyl-2-oxo-ethyl) -3-methyl-7- (3-bromo-allyl) -8-bromo-xanthine

R_fThe value: 0.68 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (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

R_fThe value: 0.60 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (ESI)⁺)：m/z＝443，445[M+H]⁺

(15)1- (2-phenyl-2-oxo-ethyl) -3-methyl-7- (2-chloro-allyl) -8-bromo-xanthine

R_fThe value: 0.77 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (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

R_fThe value: 0.77 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (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

R_fThe value: 0.77 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (ESI)⁺)：m/z＝431，433[M+H]⁺

(18)1- (2-phenyl-2-oxo-ethyl) -3-methyl-7- (1-phenylsulfanyl-butyl) -8-bromo-xanthine

R_fThe value: 0.83 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (ESI)⁺)：m/z＝527，529[M+H]⁺

(19) 3-methyl-7- (3-methyl-1-phenylsulfanyl-butyl) -8-bromo-xanthine

(the [ (1-chloro-3-methyl-butyl) thio ] -benzene used as starting material for the reaction is obtained by chlorination of [ (3-methyl-butyl) thio ] -benzene with N-chloro-succinimide in carbon tetrachloride)

R_fThe value: 0.38 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (ESI)⁺)：m/z＝423，425[M+H]⁺

(20)1, 3-dimethyl-7- (2-bromo-benzyl) -8-chloro-xanthine

R_fThe value: 0.50 (silica gel, cyclohexane/ethyl acetate ═ 1:1)

(21)1, 3-dimethyl-7- (2-chloro-benzyl) -8-chloro-xanthine

R_fThe value: 0.50 (silica gel, cyclohexane/ethyl acetate ═ 1:1)

(22) 3-cyclopropyl-7- (2-butyn-1-yl) -8-bromo-xanthine

R_fThe value: 0.45 (ready-to-use reverse phase TLC plate (e.merck), acetonitrile/water/trifluoroacetic acid 50:50:1) mass spectrometry (ESI)⁺)：m/z＝223/225[M+H]⁺

Example II

1- (2- {2- [ (ethoxycarbonyl) methoxy group]-phenyl } -2-oxo-ethyl) -3-methyl-7- (3-methyl-2-butane En-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl]-xanthine

63 mg of ethyl bromoacetate are added to a mixture of 200 mg of 1- [2- (2-hydroxy-phenyl) -2-oxo-ethyl ] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine and 63 mg of potassium carbonate in 3 ml of N, N-dimethylformamide. The reaction mixture was stirred at ambient temperature for five hours. For the treatment, it is mixed with water and the precipitate formed is filtered off with suction, washed with water and dried in a drying cabinet for three hours at 80 ℃.

Yield: 216 mg (94% of theory)

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

The following compounds are obtained in a similar manner to example II:

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

Mass spectrometry (ESI)⁺)：m/z＝624[M+H]⁺

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

R_fThe value: 0.20 (silica gel, cyclohexane/ethyl acetate ═ 6:4)

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

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

R_fThe 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-2-buten-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (ESI)⁺)：m/z＝638[M+H]⁺

(5)1- (2- {2- [ (dimethylaminocarbonyl) methoxy ] -phenyl } -2-oxo-ethyl) -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (ESI)⁺)：m/z＝652[M+H]⁺

(6)1- (2- {3- [ (methoxycarbonyl) methoxy ] -phenyl } -2-oxo-ethyl) -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (ESI)⁺)：m/z＝639[M+H]⁺

(7)1- (2- {2- [ (ethylamino-carbonyl) methoxy ] -phenyl } -2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8- [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrum (E)SI⁺)：m/z＝650[M+H]⁺

(9)1- (2- {2- [ (methylaminocarbonyl) methoxy ] -phenyl } -2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (ESI)⁺)：m/z＝623[M+H]⁺

(12)1- (2- {2- [ (isopropyloxycarbonyl) methoxy ] -phenyl } -2-oxo-ethyl) -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (ESI)⁺)：m/z＝667[M+H]⁺

(13)1- (2- {2- [ (methylaminocarbonyl) methoxy ] -phenyl } -2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8- [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

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

(14)1- (2- {2- [ (methylaminocarbonyl) methoxy ] -phenyl } -2-oxo-ethyl) -3-methyl-7- ((E) -2-buten-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

(the product contains some Z isomers)

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

Mass spectrometry (ESI)⁺)：m/z＝624[M+H]⁺

(15)1- (2- {2- [ (ethylamino-carbonyl) methoxy ] -phenyl } -2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8- [ (S) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (ESI)⁺)：m/z＝636[M+H]⁺

(16)1- (2- {2- [ (methylaminocarbonyl) methoxy ] -phenyl } -2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8- [ (S) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

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

(17)1- (2- {2- [ (methoxycarbonyl) methoxy ] -phenyl } -2-oxo-ethyl) -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (ESI)⁺)：m/z＝639[M+H]⁺

(18)1- (2- {2- [ (methylaminocarbonyl) methoxy ] -phenyl } -2-oxo-ethyl) -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [ (S) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (ESI)⁺)：m/z＝638[M+H]⁺

(19)2- (2-acetyl-phenoxy) -N-ethyl-acetamide

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

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

(22)2- (2-acetyl-phenoxy) -N-methyl-acetamide

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (ESI)⁺)：m/z＝607[M+H]⁺

(24)1- {2- [2- (1-ethoxycarbonyl-1-methyl-ethoxy) -phenyl ] -2-oxo-ethyl } -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (ESI)⁺)：m/z＝590[M+H]⁺

(26)1- (2- {2- [ (methylthio) methoxy ] -phenyl } -2-oxo-ethyl } -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

(formed as the main product when 1- [2- (2-hydroxy-phenyl) -2-oxo-ethyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine is reacted with 1-chloro-3, 3-dimethyl-butan-2-one)

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

Example III

1- [2- (2-hydroxy-phenyl) -2-oxo-ethyl]-3-methyl-7- (3-methyl-2-butene-1-) 8- [3- (tert-Butoxycarbonylamino) -piperidin-1-yl]-xanthine

1.30 g of 3-tert-butoxycarbonylamino-piperidine are added to a mixture of 2.51 g of 1- [2- (2-hydroxy-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 was stirred at 60 ℃ for 18 hours. For the treatment, it is mixed with water and the precipitate formed is filtered off with suction. The solid crude product was dissolved in ethyl acetate, and the solution was dried over magnesium sulfate and evaporated to dryness. The residue in the flask was subjected to silica gel column chromatography with cyclohexane/ethyl acetate (10:1 to 1:1) as eluent.

Yield: 2.56 g (91% of theory)

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

The following compounds are obtained in a similar manner to example III:

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

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (ESI) ⁺)：m/z＝565[M+H]⁺

(3) 3-methyl-7- (2-cyano-benzyl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.90 (silica gel, dichloromethane/methanol ═ 9:1)

Mass spectrometry (ESI)^-)：m/z＝478[M-H]^-

(4) 1-methyl-3- [ (methoxycarbonyl) methyl ] -7- (2-cyano-benzyl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (ESI)⁺)：m/z＝552[M+H]⁺

(5) 1-methyl-3-cyanomethyl-7- (2-cyano-benzyl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (ESI)⁺)：m/z＝519[M+H]⁺

(6) 1-methyl-3- (2-propyn-1-yl) -7- (2-cyano-benzyl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

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

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

(8) 1-methyl-3- (2-propen-1-yl) -7- (2-cyano-benzyl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (ESI)⁺)：m/z＝520[M+H]⁺

(9)1- (2-phenyl-2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

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

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

(11) 1-methyl-3-phenyl-7- (2-cyano-benzyl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (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- [ (S) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

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

(13)1- [ (cinnolin-4-yl) methyl ] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine in admixture with 1- [ (1, 4-dihydro-cinnolin-4-yl) methyl ] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.62 (silica gel, ethyl acetate)

(14)1- ({ 4-oxo-3- [ (2-trimethylsilyl-ethoxy) methyl ] -3, 4-dihydro-2, 3-naphthyridin-1-yl } methyl) -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

(carried out with potassium carbonate in the presence of Hunig's base)

R_fThe value: 0.27 (silica gel, cyclohexane/ethyl acetate ═ 1:1)

Mass spectrometry (ESI)⁺)：m/z＝720[M+H]⁺

(15)1- [ (isoquinolin-3-yl) methyl ] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.31 (silica gel, ethyl acetate/petroleum ether ═ 7:3)

Mass spectrometry (ESI)⁺)：m/z＝574[M+H]⁺

(16)1- [ (3-methyl-4-oxo-3, 4-dihydro-2, 3-naphthyridin-1-yl) methyl ] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.45 (silica gel, dichloromethane/methanol/concentrated ammonia 95:5)

Mass spectrometry (ESI)⁺)：m/z＝605[M+H]⁺

(17) 3-methyl-7- (2, 3-dimethyl-2-buten-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

(with potassium carbonate)

R_fThe value: 0.42 (silica gel, dichloromethane/methanol ═ 20:1)

Mass spectrometry (ESI)⁺)：m/z＝447[M+H]⁺

(18) 3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine (over potassium carbonate)

Melting point: 237 ℃ 235-

Mass spectrometry (ESI)⁺)：m/z＝417[M+H]⁺

(19)1- [ (quinolin-4-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

(with potassium carbonate)

R_fThe value: 0.36 (silica gel, ethyl acetate)

Mass spectrometry (ESI)⁺)：m/z＝558[M+H]⁺

(20)1- [ (isoquinolin-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

(with potassium carbonate)

R_fThe value: 0.71 (silica gel, ethyl acetate)

Mass spectrometry (ESI)⁺)：m/z＝558[M+H]⁺

(21)1- [ (isoquinolin-1-yl) methyl ] -3-methyl-7- ((E) -2-buten-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

(carried out on potassium carbonate; the product contains about 20% of the Z isomer)

R_fThe value: 0.24 (silica gel, ethyl acetate/petroleum ether ═ 1:1)

Mass spectrometry (ESI)⁺)：m/z＝560[M+H]⁺

(22) 3-methyl-7- (2-butyn-1-yl) -8- [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

(with potassium carbonate)

R_fThe value: 0.64 (silica gel, ethyl acetate)

Mass spectrometry (ESI)⁺)：m/z＝417[M+H]⁺

(23) 3-methyl-7- (2-butyn-1-yl) -8- [ (S) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

(with potassium carbonate)

R_fThe value: 0.64 (silica gel, ethyl acetate)

Mass spectrometry (ESI)⁺)：m/z＝417[M+H]⁺

(24) 3-methyl-7- ((E) -2-buten-1-yl) -8- [ (S) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

(the product contains about 15% of the Z isomer)

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

Mass spectrometry (ESI)⁺)：m/z＝419[M+H]⁺

(25) 3-methyl-7- ((E) -2-buten-1-yl) -8- [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

(the product contains about 15% of the Z isomer)

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

Mass spectrometry (ESI)⁺)：m/z＝419[M+H]⁺

(26)1- [2- (2-hydroxy-phenyl) -2-oxo-ethyl ] -3-methyl-7- (2-butyn-1-yl) -8- [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (ESI)⁺)：m/z＝578[M+H]⁺

(28)1- (2-phenyl-2-oxo-ethyl) -3-methyl-7- [ (1-cyclopenten-1-yl) methyl ] -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (ESI)⁺)：m/z＝563[M+H]⁺

(29)1- [2- (2-hydroxy-phenyl) -2-oxo-ethyl ] -3-methyl-7- [ (1-cyclopenten-1-yl) methyl ] -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (ESI)⁺)：m/z＝579[M+H]⁺

(30) 1-methyl-3-isopropyl-7- (2-cyano-benzyl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

(the product contains about 10% of the Z isomer)

R_fThe value: 0.20 (silica gel, cyclohexane/ethyl acetate ═ 1:1)

Mass spectrometry (ESI)⁺)：m/z＝552[M+H]⁺

(33)1- (2-phenyl-2-oxo-ethyl) -3-methyl +7- ((E) -2-buten-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

(the product contains about 25% of the Z isomer)

Mass spectrometry (ESI)⁺)：m/z＝537[M+H]⁺

(34)1- [2- (2-hydroxy-phenyl) -2-oxo-ethyl ] -3-methyl-7- (2-butyn-1-yl) -8- [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

(35)1- [2- (2-hydroxy-phenyl) -2-oxo-ethyl ] -3-methyl-7- ((E) -2-buten-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

(the product contains some Z isomers)

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

Mass spectrometry (ESI)⁺)：m/z＝553[M+H]⁺

(36)1- [2- (2-hydroxy-phenyl) -2-oxo-ethyl ] -3-methyl-7- (2-butyn-1-yl) -8- [ (S) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.50 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (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- [ (S) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

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

(39)1- (2-phenyl-2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8- [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (ESI)⁺)：m/z＝535[M+H]⁺

(40) 1-methyl-3- [ (2-trimethylsilyl-ethoxy) methyl ] -7- (2-cyano-benzyl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (ESI)⁺)：m/z＝610[M+H]⁺

(41) 3-methyl-7- (2-butyn-1-yl) -8- [ (S) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

(with potassium carbonate)

R_fThe value: 0.52 (silica gel, ethyl acetate)

Mass spectrometry (ESI)⁺)：m/z＝417[M+H]⁺

(42)1- (2-phenyl-2-oxo-ethyl) -3-methyl-7- (2-methyl-allyl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.46 (silica gel, 95:5 dichloromethane/methanol)

(43)1- (2-phenyl-2-oxo-ethyl) -3-methyl-7- (3-bromo-allyl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.22 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (ESI)⁺)：m/z＝601，603[M+H]⁺

(44)1- (2-phenyl-2-oxo-ethyl) -3-methyl-7- [ (furan-2-yl) methyl ] -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.41 (silica gel, dichloromethane/methanol ═ 95:5)

(45)1- (2-phenyl-2-oxo-ethyl) -3-methyl-7- (2-chloro-allyl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.49 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (ESI)⁺)：m/z＝535[M+H]⁺

(47)1- [2- (2-amino-phenyl) -2-oxo-ethyl ] -3-methyl-7- ((E) -2-buten-1-yl) -8- [ (S) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

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

Mass spectrometry (ESI)⁺)：m/z＝552[M+H]⁺

(48)1- [2- (2-Nitro-phenyl) -2-oxo-ethyl ] -3-methyl-7- ((E) -2-buten-1-yl) -8- [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.50 (silica gel, cyclohexane/ethyl acetate ═ 1:2)

(49)1- [2- (2-Nitro-phenyl) -2-oxo-ethyl ] -3-methyl-7- ((E) -2-buten-1-yl) -8- [ (S) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (ESI)⁺)：m/z＝626[M+H]⁺

(51)1- (2- { 2-oxo-3- [ (2-trimethylsilyl-ethoxy) methyl ]2, 3-dihydro-benzooxazol-7-yl } -2-oxo-ethyl) -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.48 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (ESI)⁺)：m/z＝551[M+H]⁺

(54)1- (2- { 2-oxo-3- [ (2-trimethylsilyl-ethoxy) methyl ]2, 3-dihydro-benzooxazol-4-yl } -2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.40 (silica gel, petroleum ether/ethyl acetate ═ 1:1)

Mass spectrometry (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) -8- [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (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- [ (S) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (ESI)⁺)：m/z＝615[M+H]⁺

(57)1- [ (1-methyl-1H-indol-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.80 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (ESI)⁺)：m/z＝560[M+H]⁺

(58)1- [ (quinolin-3-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.50 (silica gel, ethyl acetate)

Mass spectrometry (ESI)⁺)：m/z＝558[M+H]⁺

(59)1- { [ 1-tert-butoxycarbonylamino) -1H-indol-2-yl ] methyl } -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

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

Mass spectrometry (ESI)⁺)：m/z＝646[M+H]⁺

(60)1- [ (2-methyl-1- [ (2-trimethylsilyl-ethoxy) methyl ] -1H-benzimidazol-5-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine (mixed with 1- [ (2-methyl-3- [ (2-trimethylsilyl-ethoxy) methyl ] -3H-benzimidazol-5-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine )

R_fThe value: 0.15 (silica gel, ethyl acetate)

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.35 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (ESI)⁺)：m/z＝586[M+H]⁺

(62)1- [ (1- [ (2-trimethylsilyl-ethoxy) methyl ] -1H-benzimidazol-5-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine (in admixture with 1- [ (3- [ (2-trimethylsilyl-ethoxy) methyl ] -3H-benzimidazol-5-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine).

R_fThe value: 0.23 (silica gel, ethyl acetate)

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.46 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (ESI)⁺)：m/z＝547[M+H]⁺

(64)1- (2-phenyl-2-oxo-ethyl) -3-methyl-7- ((E) -1-buten-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.48 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (ESI)⁺)：m/z＝537[M+H]⁺

(65)1- {2- [1- (tert-Butoxycarbonyl) -1H-indol-7-yl ] -2-oxo-ethyl } -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

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

(66)1- [ (3-methyl-isoquinolin-1-yl) methyl ] -3-methyl-7- (3-methyl-1-buten-1-yl) -8- [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.40 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (ESI)⁺)：m/z＝588[M+H]⁺

(67)1, 3-dimethyl-7- (2-bromo-benzyl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.40 (silica gel, cyclohexane/ethyl acetate ═ 1:1)

(68)1, 3-dimethyl-7- (2-chloro-benzyl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe 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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

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

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

(70) 3-cyclopropyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

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

R_fThe value: 0.70 (silica gel, ethyl acetate)

(71) 3-cyclopropyl-7- (2-butyn-1-yl) -8- [ (R) -3- (tert-butyloxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.35 (ready-to-use reverse phase TLC plate (e.merck), acetonitrile/water/trifluoroacetic acid 50:50:1)

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

(72)1- [ (3-methyl-isoquinolin-1-yl) methyl ] -3-methyl-7- (2-chloro-benzyl) -8- [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

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

R_fThe 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- [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

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

(74)1- [ (4-methyl-quinazolin-2-yl) methyl ] -3-methyl-7- (2-chloro-benzyl) -8- [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Prepared by reacting (4-methyl-quinazolin-2-yl) -chloromethane with 3-methyl-7- (2-chlorobenzyl) -8-bromo-xanthine, followed by reaction with (R) -3- (tert-butoxycarbonylamino) -piperidine.

Mass spectrometry (ESI)⁺)：m/z＝645，647[M+H]⁺

(75)1- [ (4-phenyl-quinazolin-2-yl) methyl ] -3-methyl-7- (2-chloro-benzyl) -8- [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Prepared by reacting 4-phenyl-quinazolin-2-yl) -chloromethane with 3-methyl-7- (2-chlorobenzyl) -8-bromo-xanthine, followed by reaction with (R) -3- (tert-butoxycarbonylamino) -piperidine.

Mass spectrometry (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-yellow Purines

Prepared by treating 1- [2- (2-methoxy-phenyl) -2-oxo-ethyl ] -3-methyl-7- (3-methyl-2-buten-1-yl) -8-chloro-xanthine with boron tribromide in dichloromethane. The desired product was contaminated with about 20% 1- [2- (2-hydroxy-phenyl) -2-oxo-ethyl ] -3-methyl-7- (3-bromo-3-methyl-butyl) -8-chloro-xanthine.

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

The following compounds are obtained in a similar manner to example IV:

(1)1- [2- (2-hydroxy-phenyl) -2-oxo-ethyl ] -3-methyl-7- (2-butyn-1-yl) -8-bromo-xanthine

(product contaminated with about 20% 1- [2- (2-hydroxy-phenyl) -2-oxo-ethyl ] -3-methyl-7- (3-bromo-2-buten-1-yl) -8-bromo-xanthine)

Mass spectrometry (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-bromo-xanthine

Mass spectrometry (ESI)⁺)：m/z＝495，461[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 isomers)

R_fThe value: 0.60 (silica gel, cyclohexane/ethyl acetate 4;6)

Mass spectrometry (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 spectrometry (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 was stirred at ambient temperature for eight hours. After treatment with aqueous solution, the crude product was purified by chromatography on a silica gel column using cyclohexane/ethyl acetate (8:1 to 8:1) as eluent.

Yield: 2.61 (84% of theory)

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

The following compounds are obtained in a similar manner to example V:

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

(the reaction was carried out with 2-bromo-1- [3- (tert-butyldimethylsilyloxy) -phenyl ] -ethanone)

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

Mass spectrometry (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 spectrometry (ESI)⁺)：m/z＝401，403[M+H]⁺

(3)1- (2-cyano-ethyl) -3-methyl-7- (2-cyano-benzyl) -8-chloro-xanthine

Mass spectrometry (ESI)⁺)：m/z＝391，393[M+Na]⁺

(4)1- (2-phenoxy-ethyl) -3-methyl-7- (2-cyano-benzyl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.90 (silica gel, dichloromethane/methanol ═ 9:1)

Mass spectrometry (ESI)⁺)：m/z＝600[M+H]⁺

(5)1- (2-phenyl-2-oxo-ethyl) -3- [ (2-trimethylsilyl-ethoxy) methyl ] -7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (ESI)⁺)：m/z＝667[M+H]⁺

(6)1- (2-methoxy-ethyl) -3-methyl-7- (2-cyano-benzyl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.90 (silica gel, dichloromethane/methanol ═ 9:1)

Mass spectrometry (ESI)⁺)：m/z＝538[M+H]⁺

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

R_fThe value: 0.60 (silica gel, cyclohexane/ethyl acetate ═ 1:1)

Mass spectrometry (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_fThe value: 0.40 (silica gel, cyclohexane/ethyl acetate/methanol 7:2:1)

Mass spectrometry (ESI)⁺)：m/z＝432，434[M+H]⁺

(9)1- (2-phenyl-2-oxo-ethyl) -3-methyl-7- [ (2-trimethylsilyl-ethoxy) methyl ] -8-bromo-xanthine

Mass spectrometry (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_fThe value: 0.64 (silica gel, cyclohexane/ethyl acetate 3:7)

Mass spectrometry (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 spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.45 (silica gel, ethyl acetate/petroleum ether ═ 7:3)

Mass spectrum (mass spectrum)ESI⁺)：m/z＝574[M+H]⁺

(13)1- [ (2-oxo-2H-chromen-4-yl) methyl ] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

(the starting material 4-bromomethyl-chromen-2-one was prepared analogously to Kimura et al, chem.pharm.Bull.1982, 30, 552-558).

R_fThe value: 0.52 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.54 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (ESI)⁺)：m/z＝604[M+H]⁺

(15)1- [ (quinolin-4-yl) methyl ] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Melting point: 195 + 197 deg.C

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.40 (silica gel, cyclohexane/ethyl acetate ═ 1:1)

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

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

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.53 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.73 (silica gel, ethyl acetate)

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.45 (silica gel, cyclohexane/ethyl acetate ═ 1:1)

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

(in N-methylpyrrolidin-2-one, at 60 ℃ C.)

R_fThe value: 0.27 (silica gel, dichloromethane/methanol ═ 20:1)

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

(in N-methylpyrrolidin-2-one, at 60 ℃ C.)

R_fThe value: 0.35 (silica gel, dichloromethane/methanol ═ 20:1)

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

(in N-methylpyrrolidin-2-one, at 60 ℃ C.)

R_fThe value: 0.53 (silica gel, dichloromethane/methanol ═ 20:1)

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

(in N-methylpyrrolidin-2-one, at 60 ℃ C.)

R_fThe value: 0.38 (silica gel, dichloromethane/methanol ═ 20:1)

Mass spectrometry (ESI)⁺)：m/z＝565[M+H]⁺

(25)1- ((E) -3-phenyl-allyl) -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.54 (silica gel, dichloromethane/methanol/concentrated ammonia 95:5:0.1)

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

(26)1- [ (1-benzo [ b ] thiophen-3-yl) methyl ] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.75 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (ESI)⁺)：m/z＝579[M+H]⁺

(27)1- { [1- (tert-butoxycarbonyl) -indol-3-yl ] methyl } -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.61 (silica gel, dichloromethane/methanol ═ 9:1)

Mass spectrometry (ESI)⁺)：m/z＝662[M+H]⁺

(28)1- [ (biphenyl-4-yl) methyl ] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.68 (silica gel, cyclohexane/ethyl acetate ═ 1:1)

Mass spectrometry (ESI)⁺)：m/z＝599[M+H]⁺

(29)1- [ (1-naphthyl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.83 (silica gel, ethyl acetate/petroleum ether ═ 4:1)

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.25 (silica gel, ethyl acetate/petroleum ether ═ 4:1)

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Melting point: 163 ℃ C

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.95 (silica gel, ethyl acetate/petroleum ether ═ 4:1)

Mass spectrometry (ESI)⁺)：m/z＝531[M+H]⁺

(33)1- [ (quinazolin-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.40 (silica gel, ethyl acetate)

Mass spectrometry (ESI)⁺)：m/z＝559[M+H]+

(34)1- [ (2-methyl-naphthalen-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.80 (silica gel, ethyl acetate)

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.54 (silica gel, dichloromethane/methanol ═ 95:5)

(36)1- (2-dimethylamino-2-oxo-ethyl) -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.23 (silica gel, ethyl acetate)

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.44 (silica gel, ethyl acetate)

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.25 (silica gel, ethyl acetate)

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.30 (silica gel, ethyl acetate)

Mass spectrometry (ESI)⁺)：m/z＝604[M+H]⁺

(40)1- [ (2-methoxy-naphthalen-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.75 (silica gel, ethyl acetate)

Mass spectrometry (ESI)⁺)：m/z＝587[M+H]⁺

(41)1- [ (4-methoxy-naphthalen-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.80 (silica gel, ethyl acetate)

Mass spectrometry (ESI)⁺)：m/z＝587[M+H]⁺

(42)1- [ (3-methyl-isoquinolin-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.56 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.83 (silica gel, ethyl acetate)

Mass spectrometry (ESI)⁺)：m/z＝611[M+H]⁺

(44)1- [ (5-Nitro-naphthalen-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.78 (silica gel, ethyl acetate)

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.39 (silica gel, ethyl acetate)

Mass spectrometry (ESI)⁺)：m/z＝5441[M+H]⁺

(46)1- [ (4-methyl-isoquinolin-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.56 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (ESI)⁺)：m/z＝572[M+H]⁺

(47)1- [ (2-naphthyl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.78 (silica gel, ethyl acetate)

Mass spectrometry (ESI)⁺)：m/z＝557[M+H]⁺

(48) 1-cyanomethyl-3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.80 (silica gel, ethyl acetate)

Mass spectrometry (ESI)⁺)：m/z＝456[M+H]⁺

(49)1- [ (quinolin-6-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.40 (silica gel, ethyl acetate)

Mass spectrometry (ESI)⁺)：m/z＝558[M+H]⁺

(50)1- [ (3-methoxy-naphthalen-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.83 (silica gel, ethyl acetate)

Mass spectrometry (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-buten-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.38 (silica gel, ethyl acetate/petroleum ether ═ 1:1)

Mass spectrometry (ESI)⁺)：m/z＝609[M+H]⁺

(52)1- [2- (3-methyl-2-oxo-2, 3-dihydro-benzooxazol-7-yl) -2-oxo-ethyl ] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

(with potassium tert-butoxide, in dimethyl sulfoxide)

R_fThe value: 0.48 (silica gel, ethyl acetate/petroleum ether ═ 2:1)

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (ESI)⁺)：m/z＝595[M+H]⁺

(54)1- [ (quinazolin-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (ESI)⁺)：m/z＝559[M+H]⁺

(55)1- [ (quinazolin-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [ (S) -3- (tert-butoxycarbonylamino) -piperidin-1-yl 1-xanthine

Mass spectrometry (ESI)⁺)：m/z＝559[M+H]⁺

(56)1- [ (quinazolin-2-yl) methyl ] -3-methyl-7- ((E) -2-buten-1-yl) -8- [ (S) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

(the product contains about 15% of the Z isomer)

R_fThe value: 0.30 (silica gel, ethyl acetate/cyclohexane ═ 8:2)

Mass spectrometry (ESI)⁺)：m/z＝561[M+H]⁺

(57)1- [ (quinazolin-2-yl) methyl ] -3-methyl-7- ((E) -2-buten-1-yl) -8- [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

(the product contains about 15% of the Z isomer)

R_fThe value: 0.30 (silica gel, ethyl acetate/cyclohexane ═ 8:2)

Mass spectrometry (ESI)⁺)：m/z＝561[M+H]⁺

(58)1- [ (3-methyl-isoquinolin-1-yl) methyl ] -3-methyl-7- ((E) -2-buten-1-yl) -8- [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

(the product contains about 17% of the Z isomer)

R_fThe value: 0.58 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (ESI)⁺)：m/z＝574[M+H]⁺

(59)1- [ (3-methyl-isoquinolin-1-yl) methyl ] -3-methyl-7- ((E) -2-buten-1-yl) -8- [ (S) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

(the product contains about 17% of the Z isomer)

R_fThe value: 0.58 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (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 spectrometry (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-bromo-xanthine

Mass spectrometry (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-bromo-xanthine

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.35 (silica gel, dichloromethane/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% of the Z isomer)

R_fThe value: 0.58 (silica gel, cyclohexane/ethyl acetate 4:6)

Mass spectrometry (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 isomers)

R_fThe value: 0.30 (silica gel, cyclohexane/ethyl acetate ═ 1:1)

Mass spectrometry (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

R_fThe value: 0.77 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

(the product contains about 20% of the Z isomer)

Mass spectrometry (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 spectrometry (ESI)⁺)：m/z＝461，463[M+H]⁺

(69)1- (2-phenyl-2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8-bromo-xanthine

R_fThe value: 0.61 (silica gel, cyclohexane/ethyl acetate 4:6)

(70)1- (2- {2- [ (ethylamino-carbonyl) methoxy ] -phenyl } -2-oxo-ethyl) -3-methyl-7- ((E) -2-buten-1-yl) -8- [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

(the product contains about 17% of the Z isomer)

Mass spectrometry (ESI)⁺)：m/z＝638[M+H]⁺

(71)1- (2-phenyl-2-oxo-ethyl) -3-methyl-7- ((E) -2-buten-1-yl) -8- [ (S) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

(the product contains about 18% of the Z isomer)

R_fThe value: 0.35 (silica gel, cyclohexane/ethyl acetate ═ 6:4)

Mass spectrometry (ESI)⁺)：m/z＝537[M+H]⁺

(72)1- [2- (2-Nitro-phenyl) -2-oxo-ethyl ] -3-methyl-7- (2-butyn-1-yl) -8- [ (S) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.60 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (ESI)⁺)：m/z＝580[M+H]⁺

(73)1- [ (3-methyl-isoquinolin-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [ (S) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.52 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (ESI)⁺)：m/z＝572[M+H]⁺

(76)1- [ (4-methyl-isoquinolin-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.52 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (ESI)⁺)：m/z＝574[M+H]⁺

(78)1- [ (4-methyl-isoquinolin-1-yl) methyl ] -3-methyl-7- ((E) -2-buten-1-yl) -8- [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.52 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (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- [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.18 (silica gel, ethyl acetate/petroleum ether ═ 1:1)

Mass spectrometry (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- [ (S) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (ESI)⁺)：m/z＝593[M+H]⁺

(81)1- [ (4-methoxy-naphthalen-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [ (S) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.56 (silica gel, petroleum ether/ethyl acetate ═ 1:2)

Mass spectrometry (ESI)⁺)：m/z＝587[M+H]⁺

(82)1- [ (4-methoxy-naphthalen-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (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- [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.86 (silica gel, ethyl acetate/petroleum ether ═ 4:1)

Mass spectrometry (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- [ (S) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.86 (silica gel, ethyl acetate/petroleum ether ═ 4:1)

Mass spectrometry (ESI)⁺)：m/z＝579[M+H]⁺

(85)1- [ (4-methyl-quinazolin-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [ (S) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.48 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (ESI)⁺)：m/z＝573[M+H]⁺

(86)1- [ (4-methyl-quinazolin-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.48 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (ESI)⁺)：m/z＝573[M+H]⁺

(87)1- [2- (3-methyl-2-oxo-2, 3-dihydro-benzooxazol-4-yl) -2-oxo-ethyl ] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.50 (silica gel, petroleum ether/ethyl acetate ═ 1:2)

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

(88)1- (2- {2- [ (ethylamino-carbonyl) methoxy ] -phenyl } -2-oxo-ethyl) -3-methyl-7- ((E) -2-buten-1-yl) -8- [ (S) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (ESI)⁺)：m/z＝638[M+H]⁺

(89)1- (2- {2- [ (methylaminocarbonyl) methoxy ] -phenyl } -2-oxo-ethyl) -3-methyl-7- ((E) -2-buten-1-yl) -8- [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.60 (silica gel, dichloromethane/methanol ═ 95:5)

(92)1- [2- (2-nitro-3-methoxy-phenyl) -2-oxo-ethyl ] -3-methyl-7- (3-methyl-2-buten-1-yl) -8-bromo-xanthine

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

(in the presence of cesium carbonate)

R_fThe value: 0.40 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (ESI)⁺)：m/z＝602[M+H]⁺

(94)1- (2- { 2-oxo-3- [ (2-trimethylsilyl-ethoxy) methyl ] -2, 3-dihydro-benzooxazol-7-yl } -2-oxo-ethyl) -3-methyl-7- (3-methyl-2-buten-1-yl) -8-bromo-xanthine

R_fThe value: 0.75 (silica gel, ethyl acetate/petroleum ether ═ 1:1)

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.44 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (ESI)⁺)：m/z＝547[M+H]⁺

(96)1- [ (quinoxalin-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.50 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (ESI)⁺)：m/z＝559[M+H]⁺

(97)1- [2- (1, 3-dimethyl-2-oxo-2, 3-dihydro-1H-benzimidazol-4-yl) -2-oxo-ethyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.50 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (ESI)⁺)：m/z＝619[M+H]⁺

(98)1- [ (quinoxalin-6-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.35 (silica gel, ethyl acetate)

Mass spectrometry (ESI)⁺)：m/z＝559[M+H]⁺

(99)1- (2- { 2-oxo-3- [ (2-trimethylsilyl-ethoxy) methyl ]2, 3-dihydro-benzooxazol-4-yl } -2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8-bromo-xanthine

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

Mass spectrometry (ESI)^-)：m/z＝600，602[M-H]^-

(100)1- [ (3-methyl-quinoxalin-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.44 (silica gel, petroleum ether/ethyl acetate ═ 1:2)

Mass spectrometry (ESI)⁺)：m/z＝573[M+H]⁺

(101)1- [ (3-phenyl-isoquinolin-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.85 (silica gel, ethyl acetate)

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.60 (silica gel, ethyl acetate/methanol ═ 3:1)

Mass spectrometry (ESI)⁺)：m/z＝586[M+H]⁺

(103)1- [ (benzofuran-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) - [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

(in the presence of cesium carbonate)

R_fThe value: 0.28 (silica gel, ethyl acetate)

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

(in the presence of cesium carbonate)

R_fThe value: 0.35 (silica gel, ethyl acetate)

Mass spectrometry (ESI)⁺)：m/z＝642[M+H]⁺

(106)1- ({4- [4- (tert-butoxycarbonyl) -piperazin-1-yl ] -quinazolin-2-yl } methyl) -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

(in the presence of cesium carbonate)

R_fThe value: 0.50 (silica gel, ethyl acetate)

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

(in the presence of cesium carbonate)

R_fThe value: 0.59 (silica gel, ethyl acetate/methanol/concentrated ammonia 95:5:0.1)

Mass spectrometry (ESI)⁺)：m/z＝628[M+H]⁺

(108)1- [2- (1-ethoxycarbonyl-3-methyl-2-oxo-2, 3-dihydro-1H-benzimidazol-4-yl) -2-oxo-ethyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.25 (silica gel, petroleum ether/ethyl acetate ═ 1:2)

Mass spectrometry (ESI)⁺)：m/z＝677[M+H]⁺

(109)1- [ (4-cyano-naphthalen-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.77 (silica gel)Dichloromethane/methanol/concentrated ammonia 95:10:1)

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.25 (silica gel, ethyl acetate)

Mass spectrometry (ESI)⁺)：m/z＝561[M+H]⁺

(112)1- [ (8-methoxy-quinolin-5-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.60 (silica gel, ethyl acetate/methanol ═ 9:1)

Mass spectrometry (ESI)⁺)：m/z＝588[M+H]⁺

(113)1- [ (5-methoxy-quinolin-8-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.40 (silica gel, dichloromethane/methanol ═ 20:1)

Mass spectrometry (ESI)⁺)：m/z＝588[M+H]⁺

(114)1- [ (4-phenyl-quinazolin-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.50 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (ESI)⁺)：m/z＝561[M+H]⁺

(116)1- (2-oxo-4-phenyl-butyl) -3-methyl-7- (2-butyn-1-yl) -8- [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (ESI)⁺)：m/z＝563[M+H]⁺

(117)1- (2- { 2-oxo-1, 3-bis- [ (2-trimethylsilyl-ethoxy) methyl ] -2, 3-dihydro-1H-benzimidazol-4-yl } -2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.50 (silica gel, ethyl acetate/petroleum ether ═ 1:1)

Mass spectrometry (ESI)⁺)：m/z＝851[M+H]⁺

(118)1- [ (3-difluoromethyl-isoquinolin-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

(3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine as by-product of the reaction with 1-chloromethyl-3-trifluoromethyl 3, 4-dihydro-isoquinoline)

R_fThe value: 0.75 (aluminum oxide, petroleum ether/ethyl acetate 1:2)

Mass spectrometry (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) -8-bromo-xanthine

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.50 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.50 (silica gel, dichloromethane/methanol/concentrated ammonia 90:10:1)

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

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

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.60 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (ESI)⁺)：m/z＝637[M+H]⁺

(124)1- [ (4-isopropyl-quinazolin-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.50 (silica gel, ethyl acetate/petroleum ether ═ 8:2)

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe 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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.50 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.54 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (ESI)⁺)：m/z＝585[M+H]⁺

(128)1- [ (5-methoxy-isoquinolin-8-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.50 (silica gel, ethyl acetate/methanol ═ 24:1)

Mass spectrometry (ESI)⁺)：m/z＝588[M+H]⁺

(129)1- [ (3-difluoromethyl-isoquinolin-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.75 (aluminum oxide, petroleum ether/ethyl acetate 1:2)

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.75 (silica gel, ethyl acetate)

Mass spectrometry (ESI)⁺)：m/z＝625[M+H]⁺

(132) 1-methoxycarbonylmethyl-3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (ESI)⁺)：m/z＝489[M+H]⁺

(133)1- [ (4-phenyl-quinazolin-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

(in the presence of cesium carbonate)

R_fThe value: 0.40 (silica gel, ethyl acetate)

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.55 (silica gel, ethyl acetate/petroleum ether ═ 8:2)

Mass spectrometry (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

R_fThe value: 0.55 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (ESI)⁺)：m/z＝466，468M+H]⁺

(137)1- [ (3, 4-dimethyl-6, 7-dihydro-5H- [2] pyridin-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.65 (alumina, ethyl acetate/petroleum ether ═ 3:1)

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.40 (alumina, dichloromethane/methanol ═ 20:1)

Mass spectrometry (ESI)⁺)：m/z＝590[M+H]⁺

(139)1- {2- [1- (tert-Butoxycarbonyl) -1H-indol-4-yl ] -2-oxo-ethyl } -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.55 (silica gel, petroleum ether/ethyl acetate ═ 1:2)

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (ESI)⁺)：m/z＝587[M]⁺

(141)1- ({1- [ (2-trimethylsilyl-ethoxy) methyl ] -2-oxo-1, 2-dihydro-quinolin-6-yl } methyl) -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (ESI)⁺)：m/z＝601[M+H]⁺

(143)1- [ (8-methyl-quinoxalin-6-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (ESI)⁺)：m/z＝573[M+H]⁺

(144)1- [ (4-methyl-2, 3-naphthyridin-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.65 (silica gel, dichloromethane/methanol ═ 9:1)

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.65 (silica gel, dichloromethane/ethyl acetate ═ 1:1)

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.80 (silica gel, dichloromethane/methanol/concentrated ammonia 90:10:1)

Mass spectrometry (ESI)⁺)：m/z＝623[M+H]⁺

(147)1- {2- [1- (tert-butoxycarbonyl) -1H-indol-7-yl ] -2-oxo-ethyl } -3-methyl-7- (2-butyn-1-yl) -8-bromo-xanthine

R_fThe value: 0.83 (silica gel, dichloromethane/methanol ═ 95:5)

(148)1- [ (E) -3- (2-Nitro-phenyl) -2-propen-1-yl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (ESI)⁺)：m/z＝623[M+H]⁺

(150)1- [ (4-Nitro-naphthalen-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.41 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (ESI)⁺)：m/z＝602[M+H]⁺

(151)1- [ (benzoxazol-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

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

Mass spectrometry (ESI)⁺)：m/z＝548[M+H]⁺

(152)1- [ (5-Nitro-benzoxazol-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.50 (silica gel, cyclohexane/Ethyl acetate)Ester/methanol ═ 5:4:1)

Mass spectrometry (ESI)⁺)：m/z＝593[M+H]⁺

(153)1- [ (3-methyl-isoquinolin-1-yl) methyl ] -3-methyl-7- (3-methyl-1-buten-1-yl) -8-bromo-xanthine

R_fThe value: 0.65 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (ESI)⁺)：m/z＝468，470[M+H]⁺

(154)1- [ (quinolin-7-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (ESI)⁺)：m/z＝558[M+H]⁺

(155)1- [ ([1, 5] naphthyridin-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

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

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.32 (silica gel, dichloromethane/methanol 96:4)

Mass spectrometry (ESI)⁺)：m/z＝601[M+H]⁺

(158)1- [ ([1, 6] naphthyridin-5-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

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

Mass spectrometry (ESI)⁺)：m/z＝559[M+H]⁺

(159)1- [ ([1, 8] naphthyridin-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

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

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.47 (silica gel, petroleum ether/ethyl acetate ═ 1:1)

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.39 (silica gel, ethyl acetate)

Mass spectrometry (ESI)⁺)：m/z＝559[M+H]⁺

(162)1- [2- (3-methyl-2-oxo-2, 3-dihydro-benzooxazol-4-yl) -2-oxo-ethyl ] -3-methyl-7- (2-butyn-1-yl) -8- [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.60 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (ESI)⁺)：m/z＝606[M+H]⁺

(163)1- [ (8-phenyl-quinoxalin-6-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [ (R-3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.48 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (ESI)⁺)：m/z＝356[M+H]⁺

(164)1- [ ([1, 5] naphthyridin-4-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.25 (silica gel, ethyl acetate/petroleum ether ═ 4:1)

Mass spectrometry (ESI)⁺)：m/z＝559[M+H]⁺

(165)1- ((E) -3-pentafluorophenyl-allyl) -3-methyl-7- (2-butyn-1-yl) -8- [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (ESI)⁺)：m/z＝601[M+H]⁺

(169)1- [ (3-trifluoromethyl-isoquinolin-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

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

Mass spectrometry (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- [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.38 (silica gel, cyclohexane/ethyl acetate ═ 1:1)

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.65 (silica gel, dichloromethane/ethyl acetate ═ 1:1)

Mass spectrometry (ESI)⁺)：m/z＝622，624[M+H]⁺

(173)1- [ (4-ethoxyquinazolin-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.25 (silica gel, dichloromethane/ethyl acetate ═ 1:1)

Mass spectrometry (ESI)⁺)：m/z＝603[M+H]⁺

(174)1- [ (4-Isopropyloxy-quinazolin-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.40 (silica gel, dichloromethane/ethyl acetate ═ 1:1)

Mass spectrometry (ESI)⁺)：m/z＝617[M+H]⁺

(175)1- [ (2-methyl-benzothiazol-6-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.56 (silica gel, dichloromethane/ethyl acetate ═ 1:1)

Mass spectrometry (ESI)⁺)：m/z＝578[M+H]⁺

(176)1- [ (3-phenyl-isoquinolin-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.75 (silica gel, dichloromethane/ethyl acetate ═ 1:1)

Mass spectrometry (ESI)⁺)：m/z＝634[M+H]⁺

(177)1- [ (4-Phenyloxy-quinazolin-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.35 (silica gel, dichloromethane/ethyl acetate ═ 1:1)

Mass spectrometry (ESI) ⁺)：m/z＝651[M+H]⁺

(178)1- [ (4-phenyl-quinazolin-2-yl) methyl ] -3-cyclopropyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.45 (silica gel, dichloromethane/ethyl acetate ═ 1:1)

Mass spectrometry (ESI)⁺)：m/z＝661[M+H]⁺

(179)1- [ (3-methyl-isoquinolin-1-yl) methyl ] -3-cyclopropyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.50 (silica gel, dichloromethane/ethyl acetate ═ 1:1)

Mass spectrometry (ESI)⁺)：m/z＝598[M+H]⁺

(180)1- [2- (3-difluoromethoxy-phenyl) -2-oxo-ethyl ] -3-methyl-7- (2-butyn-1-yl) -8- [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.77 (silica gel, dichloromethane/ethyl acetate ═ 1:1)

Mass spectrometry (ESI)⁺)：m/z＝601[M+H]⁺

(181)1- [ (2-phenyl-quinazolin-4-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.65 (silica gel, dichloromethane/ethyl acetate ═ 1:1)

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.57 (silica gel, dichloromethane/ethyl acetate ═ 1:1)

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.63 (silica gel, dichloromethane/ethyl acetate ═ 1:1)

Mass spectrometry (ESI)⁺)：m/z＝565[M+H]⁺

(184)1- [2- (3-trifluoromethoxy-phenyl) -2-oxo-ethyl ] -3-methyl-7- (2-butyn-1-yl) -8- (R) - [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.64 (silica gel, dichloromethane/ethyl acetate ═ 1:1)

Mass spectrometry (ESI)⁺)：m/z＝619[M+H]⁺

(185)1- [2- (biphenyl-2-yl) -2-oxo-ethyl ] -3-methyl-7- (2-butyn-1-yl) -8- [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.70 (silica gel, dichloromethane/ethyl acetate ═ 1:1)

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.75 (silica gel, dichloromethane/ethyl acetate ═ 1:1)

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.66 (silica gel, dichloromethane/ethyl acetate ═ 1:1)

Mass spectrometry (ESI)⁺)：m/z＝593[M+H]⁺

(188)1- [ (3-methyl-isoquinolin-1-yl) methyl ] -3-cyclopropyl-7- (2-butyn-1-yl) -8- [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.50 (silica gel, dichloromethane/ethyl acetate ═ 1:1)

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.50 (silica gel, dichloromethane/ethyl acetate ═ 1:1)

Mass spectrometry (ESI)⁺)：m/z＝661[M+H]⁺

(190)1- [ (4-cyano-naphthalen-1-yl) methyl ] -3-cyclopropyl-7- (2-butyn-1-yl) -8- [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.75 (silica gel, dichloromethane/ethyl acetate ═ 1:1)

Mass spectrometry (ESI)⁺)：m/z＝608[M+H]⁺

(191)1- [2- (2-Phenyloxy-phenyl) -2-oxo-ethyl ] -3-methyl-7- (2-butyn-1-yl) -8- [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.85 (silica gel, dichloromethane/ethyl acetate ═ 1:1)

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

(192)1- [2- (3-ethoxyphenyl) -2-oxo-ethyl ] -3-methyl-7- (2-butyn-1-yl) -8- [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.72 (silica gel, dichloromethane/ethyl acetate ═ 1:1)

Mass spectrometry (ESI)⁺)：m/z＝579[M+H]⁺

(193)1- [2- (3-methoxy-phenyl) -2-oxo-ethyl ] -3-methyl-7- (2-butyn-1-yl) -8- [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.67 (silica gel, dichloromethane/ethyl acetate ═ 1:1)

Mass spectrometry (ESI)⁺)：m/z＝565[M+H]⁺

(194)1- [2- (2-methoxy-phenyl) -2-oxo-ethyl ] -3-methyl-7- (2-butyn-1-yl) -8- [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.57 (silica gel, dichloromethane/ethyl acetate ═ 1:1)

Mass spectrometry (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-isoquinolin-1-yl) methyl ] -3-methyl-7- (2-bromo-benzyl) -8- [ (R) -3- (tert-butoxycarbonylamino) -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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.55 (silica gel, ethyl acetate/petroleum ether ═ 2:1)

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

Example VI

1- (2- {3- [ (methanesulfinyl) methoxy group]-phenyl } -2-oxo-ethyl) -3-methyl-7- (3-methyl) -2-buten-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl]-xanthine

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

Yield: 299 mg (73% of theory)

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

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

The following compounds are obtained in a similar manner to example VI:

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

R_fThe value: 0.05 (silica gel, ethyl acetate/cyclohexane ═ 3:1)

Mass spectrometry (ESI)⁺)：m/z＝613[M+H]⁺

(2)1- (2- {2- [ (methanesulfinyl) methoxy ] -phenyl } -2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

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

Example VII

3- [ (2-trimethylsilyl-ethoxy) methyl group]-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butoxy) Carbonylamino) -piperidin-1-yl]-xanthine

236. mu.l of 1, 8-diazabicyclo [5.4.0] undec-7-ene was added dropwise to 630 mg of 7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine in 11 ml of acetonitrile. The solution was stirred at ambient temperature for two hours, then the acetonitrile was distilled off in vacuo. The residue in the flask was dissolved in 11 ml of N, N-dimethylformamide and mixed with 258 mg of (2-trimethylsilyl-ethoxy) chloromethane. The reaction mixture was stirred at 120 ℃ for three hours. For the work-up, water is added, the precipitated starch formed is filtered off and dissolved in ethyl acetate, the solution is dried over magnesium sulfate, evaporated to dryness and chromatographed on a silica gel column with cyclohexane/ethyl acetate/methanol (6:1:0 to 0:5:1) as eluent.

Yield: 435 mg (53% of theory)

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

The following compounds are obtained in a similar manner to example VII:

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

Mass spectrometry (ESI)^-)：m/z＝396[M-H]^-

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

R_fThe value: 0.31 (silica gel, dichloromethane/methanol/concentrated ammonia 90:10:1)

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

Example VIII

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

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

Yield: 630 mg (35% of theory)

R_fThe value: 0.24 (silica gel, dichloromethane/methanol/concentrated ammonia 90:10:1)

Mass spectrometry (ESI)⁺)：m/z＝419[M+H]⁺

Example IX

2- [3- (tert-Butoxycarbonylamino) -piperidin-1-yl]-3- (3-methyl-2-buten-1-yl) -4-ethoxycarbonyl -5- { [ (ethoxycarbonylamino) carbonyl]Amino } -3H-imidazoles

2.97 ml of ethylisocyanatoformate are added to 4.00 g of 2- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -3- (3-methyl-2-buten-1-yl) -4-ethoxycarbonyl-5-amino-3H-imidazole in 90 ml of 1, 2-dimethoxyethane and the pale brown solution is heated overnight at 120 ℃ in an oil bath. Then, another 0.6 ml of ethyl isocyanate was added and heating was continued for another four hours. For workup, the reaction mixture is mixed with saturated potassium carbonate solution and extracted with ethyl acetate, the organic phase is dried over magnesium sulfate, evaporated to dryness and purified over a silica gel column with dichloromethane/methanol/concentrated ammonia in methanol (98:2:1 to 90:10:1) as eluent.

Yield: 2.27 g (45% of theory)

R_fThe value: 0.29 (silica gel, dichloromethane/methanol/concentrated ammonia 90:10:1)

Mass spectrometry (ESI)⁺)：m/z＝537[M+H]⁺

Example X

2- [3- (tert-Butoxycarbonylamino) -piperidin-1-yl ]-3- (3-methyl-2-buten-1-yl) -4-ethoxycarbonyl -5-amino-3H-imidazole

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

R_fThe value: 0.26 (alumina, ethyl acetate/petroleum ether ═ 8:2)

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

Example XI

Cyanoimino- [ N- (3-methyl-2-buten-1-yl) -N- (ethoxycarbonylmethyl) -amino]- [3- (tert-substituted-) Butoxycarbonylamino) -piperidin-1-yl]-methane

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

R_fThe value: 0.10 (silica gel, petroleum ether/ethyl acetate ═ 6:4)

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

Example XII

Cyanoimino- [ N- (3-methyl-2-buten-1-yl) -N- (ethoxycarbonylmethyl) -amino]-phenoxy- Methane

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

R_fThe value: 0.70 (silica gel, cyclohexane/ethyl acetate ═ 1:1)

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

Example XIII

Cyanoimino- [ (ethoxycarbonylmethyl) amino]-phenoxy-methyl

Prepared by reacting diphenylcyanocarboximinate with ethyl aminoacetate-hydrochloride in the presence of triethylamine in isopropanol at ambient temperature (analogously to r. besse et al Tetrahedron1990, 46, 78037-.

R_fThe value: 0.73 (silica gel, petroleum ether/ethyl acetate ═ 8:2)

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

Example XIV

1-methyl-3- [ (methoxycarbonyl) methyl group]-7- (2-cyano-benzyl) -8-chloro-xanthine

Is prepared by reacting 1-methyl-7- (2-cyano-benzyl) -8-chloro-xanthine with methyl bromoacetate in the presence of potassium carbonate in N, N-dimethylformamide at ambient temperature.

R_fThe value: 0.80 (silica gel, dichloromethane/methanol ═ 9:1)

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

The following compounds are obtained in a similar manner to example XIV:

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

Mass spectrometry (ESI)⁺)：m/z＝355，357[M+H]⁺

(2) 1-methyl-3- (2-propyn-1-yl) -7- (2-cyano-benzyl) -8-chloro-xanthine

R_fThe value: 0.80 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (ESI)⁺)：m/z＝354，356[M+H]⁺

(3) 1-methyl-3- (2-propen-1-yl) -7- (2-cyano-benzyl) -8-chloro-xanthine

R_fThe value: 0.90 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.78 (silica gel, dichloromethane/methanol/concentrated ammonia 90:10:1)

Mass spectrometry (ESI)⁺)：m/z＝576[M+H]⁺

(5) 1-methyl-3-isopropyl-7- (2-cyano-benzyl) -8-chloro-xanthine

Mass spectrometry (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-trimethylsilyl-ethoxy) methyl ] -7- (2-cyano-benzyl) -8-chloro-xanthine with trifluoroacetic acid in dichloromethane at ambient temperature.

R_fThe value: 0.50 (silica gel, dichloromethane/methanol ═ 9:1)

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

The following compounds were obtained in a similar manner to example XV:

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

R_fThe value: 0.26 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (ESI)^-)：m/z＝361，363[M-H]^-

(2)1- [ (4-oxo-3, 4-dihydro-2, 3-naphthyridin-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 which cannot be removed chromatographically, the material is converted once more into the Doc-protected derivative and then purified chromatographically, cf. example XXV (1)).

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

Example XVI

1-methyl-3- [ (2-trimethylsilyl-ethoxy) methyl group]-7- (2-cyano-benzyl) -8-chloro-xanthine

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

Mass spectrometry (ESI)⁺)：m/z＝445，447[M+H]⁺

Example XVII

7- (2-cyano-benzyl) -xanthines

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 concentrated acetic acid, 84 ml of water and 5.2 ml of concentrated hydrochloric acid at 50 ℃.

Yield: 8.46 g (50% of theory)

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

Example XVIII

2-amino-7- (2-cyano-benzyl) -1, 7-dihydro-purin-6-one

Prepared by reacting 20.00 g of guanosine-hydrate with 22.54 g of 2-cyano-benzyl bromide in dimethyl sulfoxide at 60 ℃ followed by treatment with 57 ml of concentrated hydrochloric acid.

Yield: 18.00 g (97% of theory)

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

Example XIX

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

Prepared by treating 1- [2- (3- { [ (2-chloro-ethylamino) carbonyl ] amino } -phenyl) -2-oxo-ethyl ] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine as potassium tert-butoxide in N, N-dimethylformamide at ambient temperature.

R_fThe value: 0.50 (silica gel, dichloromethane/methanol ═ 9:1)

Example XX

1- [2- (3- { [ (2-chloro-ethylamino) carbonyl]Amino } -phenyl) -2-oxo-ethyl]-3-methyl-7- (3-methyl) 2-buten-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl]-xanthine

Prepared by reacting 221 mg of 1- [2- (3-amino-phenyl) -2-oxo-ethyl ] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine with 60 μ l of 2-chloroethyl isocyanate in 3 ml of dichloromethane at ambient temperature.

Yield: 163 mg (64% of theory)

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

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

The following compounds were obtained in a similar manner 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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

(in N, N-dimethylformamide at 30 ℃ C.)

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

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

Example XXI

1- [2- (3-amino-phenyl) -2-oxo-ethyl]-3-methyl-7- (3-methyl-2-butene-1-) 8- [3- (tert-Butoxycarbonylamino) -piperidin-1-yl ] -phenyl]-xanthine

Is prepared by treating 1- [2- (3-nitro-phenyl) -2-oxo-ethyl ] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine with iron powder in a mixture of ethanol, water and glacial acetic acid (80:25:10) at 100 ℃.

R_fThe value: 0.55 (silica gel, cyclohexane/ethyl acetate/methanol/concentrated ammonia 50:30:20:1)

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

The following compounds are obtained in a similar manner to example XXI:

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

Mass spectrometry (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- [ (S) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.22 (silica gel, ethyl acetate)

Mass spectrometry (ESI)⁺)：m/z＝589[M+H]⁺

(4)1- [2- (2-amino-phenyl) -2-oxo-ethyl ] -3-methyl-7- [ (1-cyclopenten-1-yl) methyl ] -8-bromo-xanthine

Mass spectrometry (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% of the Z isomer)

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

Mass spectrometry (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

R_fThe value: 0.50 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (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- [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (ESI)⁺)：m/z＝552[M+H]⁺

(8)1- [2- (2-amino-phenyl) -2-oxo-ethyl ] -3-methyl-7- ((E) -2-buten-1-yl) -8- [ (S) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.82 (silica gel, ethyl acetate/petroleum ether ═ 4:1)

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

Example XXII

1- (2- {2- [ (ethylcarbonyl) amino group]-phenyl } -2-oxo-ethyl) -3-methyl-7- (3-methyl-2-butene -1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl]-xanthine

Prepared by reacting 248 mg of 1- [2- (2-amino-phenyl) -2-oxo-ethyl ] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine with 40 μ l of propionyl chloride in the presence of 60 μ l of pyridine in N, N-dimethylformamide at 80 ℃.

Yield: 168 mg (62% of theory)

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

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

The following compounds are obtained in a similar manner to example XXII:

(1)1- ({5- [ (methoxycarbonyl) methylamino ] -isoquinolin-1-yl } methyl) -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

(with methyl bromoacetate and potassium carbonate)

R_fThe value: 0.42 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

(the product contains about 10% of the Z isomer)

Mass spectrometry (ESI)⁺)：m/z＝594[M+H]⁺

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

(the product contains about 10% of the Z isomer)

Mass spectrometry (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- [ (S) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

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

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

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

Mass spectrometry (ESI)⁺)：m/z＝592[M+H]⁺

(6)1- (2- {2- [ (isopropylcarbonyl) amino ] -phenyl } -2-oxo-ethyl ] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.25 (silica gel, cyclohexane/ethyl acetate ═ 1:1)

Mass spectrometry (ESI)⁺)：m/z＝636[M+H]⁺

(7)1- (2- {2- [ (isopropylcarbonyl) amino ] -phenyl } -2-oxo-ethyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.44 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (ESI)⁺)：m/z＝620[M+H]⁺

(8)1- [2- (2-acetylamino-phenyl) -2-oxo-ethyl ] -3-methyl-7- (2-butyn-1-yl) -8- [ (S) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

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

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.44 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (ESI)⁺)：m/z＝620[M+H]⁺

(10)1- (2- {2- [ (methoxycarbonyl) amino ] -phenyl } -2-oxo-ethyl) -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

(in acetonitrile, at 55 ℃ C.)

R_fThe value: 0.25 (silica gel, cyclohexane/ethyl acetate ═1:1)

Mass spectrometry (ESI)⁺)：m/z＝624[M+H]⁺

(11)1- (2- {2- [ (isopropylcarbonyl) amino ] -phenyl } -2-oxo-ethyl ] -3-methyl-7- ((E) -2-buten-1-yl) -8- [ (S) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

(in acetonitrile, at 65 ℃ C.)

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

Mass spectrometry (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- [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (ESI)⁺)：m/z＝608[M+H]⁺

(13)1- [2- (2-acetylamino-phenyl) -2-oxo-ethyl ] -3-methyl-7- ((E) -2-buten-1-yl) -8- [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (ESI) ⁺)：m/z＝594[M+H]⁺

(14)1- [2- (2-acetylamino-phenyl) -2-oxo-ethyl ] -3-methyl-7- ((E) -2-buten-1-yl) -8- [ (S) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.28 (silica gel, cyclohexane/ethyl acetate/isopropanol-8: 1:1)

Mass spectrometry (ESI)⁺)：m/z＝594[M+H]⁺

(15)1- (2- {2- [ (isopropylcarbonyl) amino ] -phenyl } -2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8- [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.90 (silica gel, dichloromethane/methanol ═ 9:1)

(16)1- (2- {2- [ (isopropylcarbonyl) amino ] -phenyl } -2-oxo-ethyl) -3-methyl-7- ((E) 2-buten-1-yl) -8- [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

(in 1, 2-dichloroethane, at 45 ℃ C.)

R_fThe value: 0.30 (silica gel, cyclohexane/ethyl acetate/isopropanol-8: 1:1)

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

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

Mass spectrometry (ESI)⁺)：m/z＝608[M+H]⁺

(18)1- (2- {2- [ (ethylcarbonyl) amino ] -phenyl } -2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8- [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.22 (silica gel, dichloromethane/methanol ═ 95:5)

(20)1- (2- {2- [ (phenylcarbonyl) amino ] -phenyl } -2-oxo-ethyl) -3-methyl-7- ((E) -2-buten-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

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

Mass spectrometry (ESI)⁺)：m/z＝656[M+H]⁺

(21)1- (2- {2- [ (cyclopropylcarbonyl) amino ] -phenyl } -2-oxo-ethyl) -3-methyl-7- [ (1-cyclopenten-1-yl) methyl ] -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

(with Hunig's base with 4-dimethylamino-pyridine in dichloromethane)

R_fThe value: 0.60 (silica gel, dichloromethane/methanol ═ 18:1)

Example XXIII

1- (2- {3- [ (methoxycarbonyl) methoxy group]-phenyl } -2-oxo-ethyl) -3-methyl-7- (3-methyl-2-butane EN-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-butoxycarbonylamino) piperidin-1-yl) -xanthine with trifluoroacetic acid in dichloromethane at ambient temperature.

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

The following compounds are obtained in a similar manner to example XXIII:

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

Mass spectrometry (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 dichloromethane was stirred at ambient temperature in the presence of 100 mg of 4A molecular sieve for four days. Then, 320 mg of phenylboronic acid was added and the reaction mixture was stirred at ambient temperature for another day. For workup, the mixture was filtered through talc and washed with ethyl acetate. The filtrate was evaporated to dryness and chromatographed on silica gel column with cyclohexane/ethyl acetate (7:3 to 1:1) as eluent.

Yield: 142 mg (14% of theory)

Mass spectrometry (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-butoxycarbonylamino) Radical) -piperidin-1-yl radical]-xanthine

Is prepared by reacting 1- (2-phenyl-2-oxo-ethyl) -7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine with di-tert-butyl pyrocarbonate in the presence of Hunig's base in dichloromethane at ambient temperature.

R_fThe value: 0.27 (silica gel, dichloromethane/methanol/concentrated ammonia 90:10:1)

The following compounds are obtained in a similar manner to example XXV:

(1)1- [ (4-oxo-3, 4-dihydro-2, 3-naphthyridin-1-yl) methyl ] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl) -xanthine

R_fThe value: 0.27 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (ESI)⁺)：m/z＝591[M+H]⁺

(2) 7-acetyl-1- (tert-butoxycarbonyl) -1H-indole

R_fThe value: 0.82 (silica gel, dichloromethane/petroleum ether/ethyl acetate)Ester is 5:4:1)

Mass spectrometry (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-cinnolin-4-yl) methyl]-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 (cf. example XXVII) are 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 was mixed with 0.92 ml of diethyl azodicarboxylate and stirred at ambient temperature overnight. It is then evaporated to dryness and chromatographed on a silica gel column using ethyl acetate/petroleum ether (7:3 to 0:1) as eluent. A mixture of cinnoline and a 1, 4-dihydro-cinnoline compound is obtained.

Yield: 660 mg (52% of theory)

R_fThe value: 0.60 (silica gel, ethyl acetate/petroleum ether ═ 7:3)

The following compounds are obtained in a similar manner to example XXVI:

(1)1- ({ 4-oxo-3- [ (2-trimethylsilyl-ethoxy) methyl ] -3, 4-dihydro-2, 3-naphthyridin-1-yl } methyl) -3-methyl-7- (3-methyl-2-buten-1-yl) -8-chloro-xanthine

R_fThe value: 0.85 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (ESI)⁺)：m/z＝557，559[M+H]⁺

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

Melting point: 194 ℃ C

Mass spectrometry (ESI)⁺)：m/z＝410，412[M+H]⁺

(3)1- [ (3-methyl-4-oxo-3, 4-dihydro-2, 3-naphthyridin-1-yl) methyl ] -3-methyl-7- (3-methyl-2-buten-1-yl) -8-chloro-xanthine

R_fThe value: 0.66 (silica gel, ethyl acetate)

Mass spectrometry (ESI)⁺)：m/z＝441，443[M+H]⁺

(4)1- [ (quinolin-4-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8-bromo-xanthine

(with potassium carbonate)

R_fThe value: 0.45 (silica gel, ethyl acetate)

Mass spectrometry (ESI)⁺)：m/z＝438，440[M+H]⁺

(5)1- [ (isoquinolin-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8-bromo-xanthine

R_fThe value: 0.78 (silica gel, ethyl acetate)

Mass spectrometry (ESI)⁺)：m/z＝438，440[M+H]⁺

(6)1- [ (4-dimethylamino-tea-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.80 (silica gel, ethyl acetate)

Mass spectrometry (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% of the Z isomer)

R_fThe value: 0.71 (silica gel, ethyl acetate)

Mass spectrometry (ESI)⁺)：m/z＝440，442[M+H]⁺

(8)1- [ (1-methyl-1H-indol-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8-bromo-xanthine

R_fThe value: 0.95 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (ESI)⁺)：m/z＝440，442[M+H]⁺

(9)1- [ (quinolin-3-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8-bromo-xanthine

R_fThe value: 0.55 (silica gel, ethyl acetate/petroleum ether ═ 8:2)

Mass spectrometry (ESI)⁺)：m/z＝438，440[M+H]⁺

(10)1- { [1- (tert-butoxycarbonylamino) -1H-indol-2-yl ] methyl } -3-methyl-7- (2-butyn-1-yl) -8-bromo-xanthine

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

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

(11)1- ({ 2-methyl-1- [ (2-trimethylsilyl-ethoxy) methyl ] -1H-benzimidazol-5-yl } methyl) -3-methyl-7- (2-butyn-1-yl) -8-bromo-xanthine (mixed with 1- ({ 2-methyl-3- [ (2-trimethylsilyl-ethoxy) methyl ] -3H-benzimidazol-5-yl } methyl) -3-methyl-7- (2-butyn-1-yl) -8-bromo-xanthine)

Mass spectrometry (ESI)⁺)：m/z＝571，573[M+H]⁺

(12)1- [ (1- [ (2-trimethylsilyl-ethoxy) methyl ] -1H-benzimidazol-5-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8-bromo-xanthine (in admixture with 1- [ (3- [ (2-trimethylsilyl-ethoxy) methyl ] -3H-benzimidazol-5-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8-bromo-xanthine)

R_fThe value: 0.50 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (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

R_fThe value: 0.35 (silica gel, petroleum ether/ethyl acetate ═ 1:2)

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

Example XXVII

(cinnolin-4-yl) -methanol with (1, 4-dihydro-cinnolin-4-yl) -methanol

A solution of 1.00 g of methyl cinnoline-4-carboxylate in 15 ml of diethyl ether is added dropwise at 0 ℃ to a suspension of 222 mg of lithium aluminum hydride in 5 ml of diethyl ether. After 1.5 hours, water was carefully added dropwise to the reaction mixture, stirred with dichloromethane and filtered by suction through a glass fiber filter. The aqueous phase was extracted with dichloromethane and the combined organic phases were dried over magnesium sulfate and evaporated to dryness. According to¹H-NMR, obtaining a mixture of cinnoline and the 1, 4-dihydro-cinnoline compound as a yellow oil, which was further reacted without any purification.

Yield: 530 mg (62% of theory)

R_fThe value: 0.63 (silica gel, ethyl acetate)

Mass spectrometry (ESI)⁺)：m/z＝161[M1+H]+ and 163[ M2+ H]+

The following compounds are obtained in a similar manner to example XXVII:

(1) { 2-methyl-1- [ (2-trimethylsilyl-ethoxy) methyl ] -1H-benzimidazol-5-yl } -methanol

(mixed with { 2-methyl-3- [ (2-trimethylsilyl-ethoxy) methyl ] -3H-benzimidazol-5-yl } -methanol)

Mass spectrometry (ESI)⁺)：m/z＝293[M+H]⁺

(2) (2, 3, 8-trimethyl-quinoxalin-6-yl) -methanol

R_fThe value: 0.45 (silica gel, petroleum ether/ethyl acetate ═ 1:2)

Mass spectrometry (ESI)⁺)：m/z＝203[M+H]⁺

(3) (8-methyl-quinoxalin-6-yl) -methanol

R_fThe value: 0.18 (silica gel, cyclohexane/ethyl acetate ═ 1:1)

Mass spectrometry (ESI)⁺)：m/z＝175[M+H]⁺

(4) (E) -3-Pentafluorophenyl-2 propen-1-ol

(with diisobutylaluminum hydride, in toluene)

Mass spectrum (EI): 224[ M ] M/z]⁺

(5) (E) -3- (2-trifluoromethyl-phenyl) -2-propen-1-ol

(with diisobutylaluminum hydride, in toluene)

(6) (E) -3- (3-trifluoromethyl-phenyl) -2-propen-1-ol

(with diisobutylaluminum hydride, in toluene)

Mass spectrum (EI): 202[ M ] M/z]⁺

(7) (E) -3- (4-trifluoromethyl-phenyl) -2-propen-1-ol

(with diisobutylaluminum hydride, in toluene)

Example XXVIII

4-hydroxymethyl-2- [ (2-trimethylsilyl-ethoxy) methyl]-2H-2, 3-naphthyridin-1-one

Prepared by treating 4-oxo-3- [ (2-trimethylsilyl-ethoxy) methyl ] -3, 4-hydrogen-2, 3-naphthyridine-1-carboxylic acid methyl ester in tetrahydrofuran at 40 ℃ with sodium borohydride.

R_fThe value: 0.55 (silica gel, cyclohexane/ethyl acetate ═ 1:1)

Mass spectrometry (ESI)⁺)：m/z＝307[M+H]⁺

The following compounds are obtained in a similar manner to example XXVIII:

(1) (3, 4-dimethyl-isoquinolin-1-yl) -methanol

(with lithium borohydride in tetrahydrofuran)

R_fThe value: 0.35 (silica gel, petroleum ether/ethyl acetate 2:1)

Mass spectrometry (ESI)⁺)：m/z＝188[M+H]⁺

(2) (3-methyl-imidazo [1, 2-a ] pyridin-2-yl) -methanol

(with lithium borohydride in tetrahydrofuran)

R_fThe value: 0.48 (silica gel, dichloromethane/methanol/concentrated ammonia 90:10:1)

Mass spectrometry (ESI)⁺)：m/z＝163[M+H]⁺

(3) (3, 4-dimethyl-6, 7-dihydro-5H- [2] pyridin-1-yl) -methanol

(with lithium borohydride in tetrahydrofuran)

R_fThe value: 0.40 (aluminum oxide, petroleum ether/ethyl acetate ═ 1:1)

Mass spectrometry (ESI)⁺)：m/z＝178[M+H]⁺

(4) (3, 4-dimethyl-5, 6, 7, 8-tetrahydro-isoquinolin-1-yl) -methanol

(with lithium borohydride in tetrahydrofuran)

R_fThe value: 0.45 (aluminum oxide, petroleum ether/ethyl acetate 3:1)

Mass spectrometry (ESI)⁺)：m/z＝192[M+H]⁺

(5) 6-hydroxymethyl-1, 2, 3, 4-tetrahydro-phenanthridine

(by lithium borohydride in tetrahydrofuran, at ambient temperature)

R_fThe value: 0.40 (silica gel, petroleum ether/ethyl acetate 2:1)

Mass spectrometry (ESI)⁺)：m/z＝214[M+H]⁺

Example XXIX

4-oxo-3- [ (2-trimethylsilyl-ethoxy) methyl group]3, 4-dihydro-2, 3-naphthyridine-1-carboxylic acid Methyl ester

Prepared by reacting 4-oxo-3, 4-dihydro-2, 3-naphthyridine-1-carboxylic acid methyl ester with (2-trimethylsilyl-ethoxy) methyl chloride in the presence of Hunig's base in dichloromethane at ambient temperature.

R_fThe value: 0.75 (silica gel, cyclohexane/ethyl acetate 6:4)

Mass spectrometry (ESI)⁺)：m/z＝335[M+H]⁺

The following compounds are obtained in a similar manner to example XXIX:

(1) 7-acetyl-3- [ (2-trimethylsilyl-ethoxy) methyl ] -3H-benzoxazol-2-one

Mass spectrometry (ESI)⁺)：m/z＝308[M+H]⁺

(2) 4-acetyl-3- [ (2-trimethylsilyl-ethoxy) methyl ] -3H-benzoxazol-2-one

R_fThe value: 0.87 (silica gel, dichloromethane/methanol 99:1)

(3) 4-acetyl-1, 3-bis- [ (2-trimethylsilyl-ethoxy) methyl ] -1, 3-dihydro-benzimidazol-2-one

(with potassium tert-butoxide in N, N-dimethylformamide)

R_fThe value: 0.90 (silica gel, petroleum ether/ethyl acetate ═ 1:1)

Mass spectrometry (ESI)⁺)：m/z＝437[M+H]⁺

(4) 6-methyl-1- [ (2-trimethylsilyl-ethoxy) methyl ] -1H-quinolin-2-one

R_fThe value: 0.78 (silica gel, petroleum ether/ethyl acetate ═ 1:1)

Mass spectrometry (ESI)⁺)：m/z＝290[M+H]⁺

(5) { 2-methyl-1- [ (2-trimethylsilyl-ethoxy) methyl ] -1H-benzimidazol-5-yl } -carboxylic acid methyl ester (mixed with { 2-methyl-3- [ (2-trimethylsilylethoxy) methyl ] -3H-benzimidazol-5-yl } -carboxymethylester)

Mass spectrometry (ESI)⁺)：m/z＝321[M+H]⁺

Example XXX

1- [2 (3-methanesulfonyl-phenyl) -2-oxo-ethyl]-3-methyl-7- (3-methyl-2-butene-1-) 8- [3- (tert-Butoxycarbonylamino) -piperidin-1-yl ]-xanthine

0.22 ml of 35% hydrogen peroxide solution with 20 mg of sodium tungstate is 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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine in 5 ml of dichloromethane. The reaction mixture was stirred at ambient temperature overnight, then 1 ml of methanol was added. After another 48 hours, an additional 1.5 ml of 35% hydrogen peroxide solution, a spatula tip of sodium tungstate and two drops of water were added. The next morning, the oxidation was complete according to thin layer chromatography, and the reaction mixture was diluted with 50 ml of dichloromethane and washed twice with 30 ml of 10% sodium thiosulfate solution. The organic phase was dried over magnesium sulfate and evaporated to dryness leaving the viscous resin which was allowed to react further without any purification.

Yield: 530 mg (100% of theory)

R_fThe value: 0.72 (silica gel, ethyl acetate)

Mass spectrometry (ESI)⁺)：m/z＝629[M+H]⁺

Example XXXI

1- [2 (3-carboxy-phenyl) -2-oxo-ethyl]-3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butyl) methyl ester -butoxycarbonylamino) -piperidin-1-yl]-xanthine

Prepared by treating 1- [2- (3-methoxycarbonyl-phenyl) -2-oxo-ethyl ] -3-methyl-7- (3-methyl-2-buten-I-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine in methanol at ambient temperature with 3M sodium hydroxide solution.

R_fThe value: 0.34 (silica gel, dichloromethane/methanol ═ 9:1)

Mass spectrometry (ESI)⁺)：m/z＝595[M+H]⁺

The following compounds are obtained in a similar manner to example XXXI:

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

R_fThe value: 0.49 (silica gel, dichloromethane/methanol ═ 9:1)

(2)1- [2- (2-carboxymethoxy-phenyl) -2-oxo-ethyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

(carried out in tetrahydrofuran with 4M potassium hydroxide solution)

Mass spectrometry (ESI)⁺)：m/z＝609[M+H]⁺

(3)1- [2- (2-carboxymethylamino-phenyl) -2-oxo-ethyl ] -3-methyl-7- ((E) -2-buten-1-yl) -8- [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

(carried out in tetrahydrofuran with 4M potassium hydroxide solution)

R_fThe value: 0.65 (silica gel, cyclohexane/ethyl acetate 3:7)

Mass spectrometry (ESI)⁺)：m/z＝610[M+H]⁺

(4) 1-carboxymethyl-3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (ESI)⁺)：m/z＝475[M+H]⁺

Example XXXII

1- {2- [3- (methylaminocarbonyl) -phenyl]-2-oxo-ethyl } -3-methyl-7- (3-methyl-2-butene-1-) 8- [3- (tert-Butoxycarbonylamino) -piperidin-1-yl]-xanthine (p-butyl acrylate)

A mixture of 190 mg of 1- [2- (3-carboxy-phenyl) -2-oxo-ethyl ] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine, 43. mu.l of 40% methylamine solution, 103 mg of O- (benzotriazol-1-yl) -N, N, N ', N' -tetramethyluronium tetrafluoroborate, 43 mg of N-hydroxybenzotriazole and 45. mu.l of triethylamine in 3 ml of tetrahydrofuran was stirred at ambient temperature for eight hours. For workup, the reaction mixture was diluted with ethyl acetate and washed with water, 10% citric acid solution, 10% potassium carbonate solution and saturated sodium chloride solution. The organic phase was evaporated to dryness and chromatographed on silica gel column with dichloromethane/methanol (98:2 to 80:20) as eluent.

Yield: 173 mg (89% of theory)

R_fThe value: 0.30 (silica gel, dichloromethane/methanol ═ 20:1)

Mass spectrometry (ESI)⁺)：m/z＝608[M+H]⁺

The following compounds are obtained in a similar manner to example XXXII:

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

R_fThe value: 0.28 (silica gel, dichloromethane/methanol ═ 20:1)

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.30 (silica gel, dichloromethane/methanol ═ 20:1)

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.30 (silica gel, dichloromethane/methanol ═ 20:1)

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.30 (silica gel,dichloromethane/methanol 20:1)

Mass spectrometry (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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

(carried out with Hunig's base in N, N-dimethylformamide)

Mass spectrometry (ESI)⁺)：m/z＝650[M+H]⁺

(6)1- (2- {2- [ (ethylamino-carbonyl) methoxy ] -phenyl } -2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

(carried out with Hunig's base in N, N-dimethylformamide)

Mass spectrometry (ESI)⁺)：m/z＝636[M+H]⁺

(7)1- (2- {2- [ 2-oxo-2- (pyrrolidin-1-yl) -ethoxy ] -phenyl } -2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

(carried out with Hunig's base in N, N-dimethylformamide)

Mass spectrometry (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-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

(carried out with Hunig's base in N, N-dimethylformamide)

Mass spectrometry (ESI)⁺)：m/z＝678[M+H]⁺

(9)1- (2- {2- [ (methylaminocarbonyl) methylamino ] -phenyl } -2-oxo-ethyl) -3-methyl-7- ((E) -2-buten-1-yl) -8- [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.40 (silica gel, cyclohexane/ethyl acetate/methanol ═ 5:4:1)

Mass spectrometry (ESI)⁺)：m/z＝623[M+H]⁺

(10)1- [ (2-amino-phenylaminocarbonyl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.40 (silica gel, cyclohexane/ethyl acetate/methanol ═ 5:4:1)

Mass spectrometry (ESI)⁺)：m/z＝565[M+H]⁺

Example XXXIII

1-chloromethyl-4-methyl-isoquinoline-hydrochloride

Prepared by treating (4-methyl-isoquinolin-1-yl) -methanol with thionyl chloride in dichloromethane.

R_fThe value: 0.76 (silica gel, dichloromethane/methanol/concentrated ammonia 95:5:0.1)

Mass spectrometry (ESI)⁺)：m/z＝192，194[M+H]⁺

The following compounds are obtained in a similar manner to example XXXIII:

(1) 1-chloromethyl-3, 4-dimethyl-isoquinoline-hydrochloride

R_fThe value: 0.65 (silica gel, petroleum ether/ethyl acetate 2:1)

Mass spectrometry (ESI)⁺)：m/z＝206，208[M+H]⁺

(2) 5-chloromethyl-8-methoxy-quinoline-hydrochloride

Mass spectrometry (ESI)⁺)：m/z＝208，210[M+H]⁺

(3) 8-chloro-methyl-5-methoxy-quinoline-hydrochloride

Mass spectrum (EI): 207, 209[ M ] M/z]⁺

(4) 2-chloromethyl-3-methyl-imidazo [1, 2-a ] pyridine-hydrochloride

R_fThe value: 0.55 (silica gel, dichloromethane/methanol/concentrated ammonia 90:10:1)

Mass spectrometry (ESI)⁺)：m/z＝181，183[M+H]⁺

(5) 8-chloromethyl-5-methoxy-isoquinoline-hydrochloride

Mass spectrometry (ESI)⁺)：m/z＝208，210[M+H]⁺

(6) 1-chloromethyl-3, 4-dimethyl-6, 7-dihydro-5H- [2] pyridine-hydrochloride

R_fThe value: 0.50 (aluminum oxide, petroleum ether/ethyl acetate 10:1)

Mass spectrometry (ESI)⁺)：m/z＝196，198[M+H]⁺

(7) 1-chloromethyl-3, 4-dimethyl-5, 6, 7, 8-tetrahydro-isoquinoline-hydrochloride

R_fThe value: 0.50 (aluminum oxide, petroleum ether/ethyl acetate 10:1)

Mass spectrometry (ESI)⁺)：m/z＝210，212[M+H]⁺

(8) 6-chloromethyl-2, 3, 8-trimethyl-quinoxaline-hydrochloride

Mass spectrometry (ESI)⁺)：m/z＝221，223[M+H]⁺

(9) 6-chloromethyl-8-methyl-quinoxaline-hydrochloride

Mass spectrometry (ESI)⁺)：m/z＝193，195[M+H]⁺

(10) 6-chloromethyl-1, 2, 3, 4-tetrahydro-phenanthridine-hydrochloride

R_fThe value: 0.50 (silica gel, petroleum ether/ethyl acetate ═ 5:1)

Mass spectrometry (ESI)⁺)：m/z＝232，234[M+H]⁺

Example XXXIV

1- [ (4-oxo-3, 4-dihydro-quinazolin-2-yl) methyl group]-3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyl) amino acid -butoxycarbonylamino) -piperidin-1-yl]-xanthine

0.5 ml of 1M sodium methoxide in methanol is added dropwise at ambient temperature to a solution of 428 mg of 1-cyanomethyl-3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine in 3 ml of methanol. After about 20 minutes, the thick suspension formed was warmed in a water bath and diluted with 2 ml of methanol. Upon completion of the imido ester forming reaction according to thin layer chromatography, the reaction mixture was neutralized with 0.5 ml of 1M glacial acetic acid in methanol and mixed with 130 mg of anthranilic acid in 2 ml of methanol. Warming gave a clear solution which was stirred at ambient temperature for 2.5 hours. The reaction mixture was then gently refluxed for about 3.5 hours. After standing overnight at ambient temperature, the methanol was distilled off and the residue was stirred with cold water, filtered with suction and dried. The crude product is suspended in 5 ml of methanol, warmed and, after cooling, filtered off with suction, washed with methanol and dried in a desiccator.

Yield: 302 mg (56% of theory)

R_fThe value: 0.55 (silica gel, ethyl acetate)

Mass spectrometry (ESI)⁺)：m/z＝575[M+H]⁺

The following compounds are obtained in a similar manner to example XXXV:

(1) (4-difluoromethoxy-naphthalen-1-yl) -methanol

R_fThe value: 0.33 (silica gel, cyclohexane/ethyl acetate ═ 6:4)

Mass spectrometry (ESI)^-)：m/z＝223[M-H]^-

Example XXXV

(4-dimethylamino-naphthalen-1-yl) -methanol

Is prepared by reducing 4-dimethylamino-naphthalene-1-carbaldehyde with sodium borohydride in tetrahydrofuran aqueous solution.

R_fThe value: 0.67 (silica gel, cyclohexane/ethyl acetate ═ 1:1)

Example XXXVI

2-bromo-1- (2, 3-dihydro-benzo [1, 4]]Dioxin-5-yl) ethanones

Prepared by bromination of 1- (2, 3-dihydro-benzo [1, 4] dioxin-5-yl) -ethanone in dichloromethane while gently cooling in an ice bath. The dibromo-compound formed as a by-product was separated by column chromatography.

Mass spectrometry (ESI)⁺)：m/z＝257，259[M+H]⁺

R_fThe value: 0.92 (silica gel, dichloromethane)

The following compounds are obtained in a similar manner to example XXXVI:

(1)7- (2-bromo-acetyl) -3-methyl-3H-benzoxazol-2-one

(bromination was carried out in dioxane at 40 ℃ C.; product contaminated with about 20% dibromo-based compound)

R_fThe value: 0.44 (silica gel, petroleum ether/ethyl acetate ═ 1:1)

Mass spectrometry (ESI)⁺)：m/z＝270，272[M+H]⁺

(2) 1-benzo [1, 3] dioxol-4-yl-2-bromo-ethanones

Mass spectrometry (ESI)⁺)：m/z＝243，245[M+H]⁺

R_fThe value: 0.94 (silica gel, dichloromethane)

(3)2- [2- (2-bromo-acetyl) -phenoxy ] -N-ethyl-acetamide

(bromination is carried out with copper (II) bromide in dioxane)

Mass spectrometry (ESI)⁺)：m/z＝300，302[M+H]⁺

(4)4- (2-bromo-acetyl) -3-methyl-3H-benzoxazol-2-one

R_fThe value: 0.67 (silica gel, dichloromethane/methanol 99:1)

Mass spectrometry (ESI)⁺)：m/z＝270，272[M+H]⁺

(5)2- [2- (2-bromo-acetyl) -phenoxy ] -N-methyl-acetamide

Mass spectrometry (ESI)⁺)：m/z＝386，388[M+H]⁺

(6)7- (2-bromo-acetyl) -3- [ (2-trimethylsilyl-ethoxy) methyl ] -3H-benzoxazol-2-one

R_fThe value: 0.84 (silica gel, dichloromethane/methanol 99:1)

Mass spectrometry (ESI)⁺)：m/z＝384，386[M+H]⁺

(7)4- (2-bromo-acetyl) -1, 3-dimethyl-1, 3-dihydro-benzimidazol-2-one

R_fThe value: 0.38 (silica gel, ethyl acetate/petroleum ether ═ 1:1)

Mass spectrometry (ESI)⁺)：m/z＝283，285[M+H]⁺

(8)4- (2-bromo-acetyl) -3- [ (2-trimethylsilyl-ethoxy) methyl ] -3H-benzoxazol-2-one

R_fThe value: 0.82 (silica gel, dichloromethane/methanol 99:1)

(9)4- (2-bromo-acetyl) -1-ethoxycarbonyl-3-methyl-1, 3-dihydro-benzimidazol-2-one

R_fThe value: 0.39 (silica gel, petroleum ether/ethyl acetate 2:1)

Mass spectrometry (ESI)⁺)：m/z＝341，343[M+H]⁺

(10) 2-bromo-1- (2, 2-difluoro-benzo [1, 3] dioxol-4-yl) -ethanone

Mass spectrometry (ESI)^-)：m/z＝277，279[M-H]^-

Example XXXVII

(2, 3-dihydro-benzo [1, 4 ]]Dioxin-5-yl) ethanones

Is prepared by reacting 1- (2, 3-dihydroxy-phenyl) -ethanone with 1, 2-dibromoethane in the presence of potassium carbonate in N, N-dimethylformamide at 100 ℃.

R_fThe value: 0.43 (silica gel, ethyl acetate/petroleum ether ═ 1:4)

Mass spectrometry (ESI)⁺)：m/z＝179[M+H]⁺

Example XXXVIII

1- [ (3-methyl-4-oxo-3, 4-dihydro-quinazolin-2-yl) methyl group]-3-methyl-7- (2-butyne-1-) 8- [3- (tert-Butoxycarbonylamino) -piperidin-1-yl]-xanthine

Is prepared by reacting 1- [ (4-oxo-3, 4-dihydro-quinazolin-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine with methyl iodide in the presence of potassium carbonate in N, N-dimethylformamide at ambient temperature.

R_fThe value: 0.50 (silica gel, ethyl acetate)

Mass spectrometry (ESI)⁺)：m/z＝589[M+H]⁺

The following compounds are obtained in a similar manner to example XXXVIII:

(1) 7-acetyl-3-methyl-3H-benzoxazol-2-ones

(methylation is carried out in methanol in the presence of sodium carbonate)

R_fThe value: 0.46 (silica gel, petroleum ether/ethyl acetate ═ 1:1)

Mass spectrometry (ESI)⁺)：m/z＝192[M+H]⁺

(2) 4-acetyl-3-methyl-3H-benzoxazol-2-ones

(methylation is carried out by refluxing in methanol in the presence of sodium carbonate)

R_fThe value: 0.67 (silica gel, dichloromethane/methanol 99:1)

Mass spectrometry (ESI)⁺)：m/z＝192[M+H]⁺

(3) 4-acetyl-1, 3-dimethyl-1, 3-dihydro-benzimidazol-2-one

(in the presence of potassium tert-butoxide)

R_fThe value: 0.40 (silica gel, ethyl acetate/petroleum ether ═ 2:1)

Mass spectrometry (ESI)⁺)：m/z＝205[M+H]⁺

(4) 4-acetyl-1-ethoxycarbonyl-3-methyl-1, 3-dihydro-benzimidazol-2-one

R_fThe value: 0.23 (silica gel, petroleum ether/ethyl acetate 2:1)

Mass spectrometry (ESI)⁺)：m/z＝263[M+H]⁺

(5)1- [ (1-methyl-1H-benzimidazol-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

Mass spectrometry (ESI)⁺)：m/z＝561[M+H]⁺

(6)1- { [1- (2-cyano-ethyl) -1H-benzimidazol-2-yl ] methyl } -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

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

Mass spectrometry (ESI)⁺)：m/z＝600[M+H]⁺

(7)1- ({1- [ (methylaminocarbonyl) methyl ] -1H-benzimidazol-2-yl } methyl) -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.45 (silica gel, cyclohexane/ethyl acetate/methanol ═ 5:4:1)

Mass spectrometry (ESI)⁺)：m/z＝618[M+H]⁺

(8)1- [ (1-benzyl-1H-benzimidazol-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

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

Mass spectrometry (ESI)⁺)：m/z＝637[M+H]⁺

Example XXXIX

1- [2- (2-cyanomethylamino-phenyl) -2-oxo-ethyl]-3-methyl-7- (3-methyl-2-butene-1-) 8- [3- (tert-Butoxycarbonylamino) -piperidin-1-yl]-xanthine

Is prepared by reacting 1- [2- (2-amino-phenyl) -2-oxo-ethyl ] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine with paraformaldehyde and potassium cyanide in the presence of zinc chloride in glacial acetic acid at 40 ℃.

R_fThe value: 0.45 (silica gel, cyclohexane/ethyl acetate 3:7)

Mass spectrometry (ESI)⁺)：m/z＝605[M+H]⁺

Example XL

1- [2- (2-amino-phenyl) -2-oxo-ethyl]-3-methyl-7- (2-butyn-1-yl) -8- [ (S) -3- (tert-butyl) Oxycarbonylamino) -piperidin-1-yl]-xanthine

Is prepared by reducing 1- [2- (2-nitro-phenyl) -2-oxo-ethyl ] -3-methyl-7- (2-butyn-1-yl) -8- [ (S) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine with sodium dithionite in a mixture of methyl glycol and water (2:1) at 100 ℃.

R_fThe value: 0.34 (silica gel, dichloromethane/methanol ═ 95:5)

The following compounds are obtained in a similar manner to example XL:

(1)1- [2- (2-amino-phenyl) -2-oxo-ethyl ] -3-methyl-7- (2-butyn-1-yl) -8- [ (R) -3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine

R_fThe value: 0.50 (silica gel, cyclohexane/ethyl acetate 4:6)

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 theory)

R_fThe value: 0.81 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (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 was added dropwise to 500 mg of 4-chloro-2-chloromethylquinazoline in 5 ml of tetrahydrofuran cooled in an ice bath. The reaction mixture was then stirred for an additional 3.5 hours with ice bath cooling, followed by an additional 30 minutes at ambient temperature. Then, using a rotary evaporator, the solvent was gently distilled off, and the residue was dissolved in dichloromethane. The solution was washed with saturated sodium bicarbonate solution and water, dried over magnesium sulfate, and evaporated to dryness. The solid residue is stirred with a small amount of tert-butyl methyl ether, filtered off with suction, washed with petroleum ether and dried in vacuo.

Yield: 323 mg (62% of theory)

R_fThe value: 0.60 (silica gel, cyclohexane/ethyl acetate ═ 1:1)

Mass spectrometry (ESI)⁺)：m/z＝222，224[M+H]⁺

The following compounds were obtained in a similar manner to example XLII:

(1) 2-chloromethyl-4- (morpholin-4-yl) -quinazoline

R_fThe value: 0.50 (silica gel, cyclohexane/ethyl acetate ═ 1:1)

Mass spectrometry (ESI)⁺)：m/z＝264，266[M+H]⁺

(2) 2-chloromethyl-4- (piperidin-1-yl) -quinazoline

R_fThe value: 0.70 (silica gel, cyclohexane/ethyl acetate ═ 1:1)

Mass spectrometry (ESI)⁺)：m/z＝262，264[M+H]⁺

(3)4- [4- (tert-butoxycarbonyl) -piperazin-1-yl ] -2-chloromethyl-quinazoline

R_fThe value: 0.57 (silica gel, cyclohexane/ethyl acetate ═ 1:1)

Mass spectrometry (ESI)⁺)：m/z＝363，365[M+H]⁺

(4) 2-chloromethyl-4- (pyrrolidin-1-yl) -quinazoline

R_fThe value: 0.50 (silica gel, cyclohexane/ethyl acetate ═ 1:1)

Mass spectrometry (ESI)⁺)：m/z＝248，250[M+H]⁺

(5) 2-chloromethyl-4-ethoxyquinazoline

(the reaction was carried out with sodium ethoxide in ethanol at ambient temperature).

R_fThe value: 0.50 (silica gel, cyclohexane/ethyl acetate 3:1)

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

(6) 2-chloromethyl-4-isopropyloxy-quinazoline

(the reaction was carried out in isopropanol at ambient temperature with sodium isopropoxide).

R_fThe value: 0.70 (silica gel, cyclohexane/ethyl acetate ═ 3:1)

Mass spectrometry (ESI)⁺)：m/z＝237，239[M+H]⁺

(7) 2-chloromethyl-4-phenyloxy-quinazolines

(the reaction was carried out with sodium hydride and phenol in tetrahydrofuran at ambient temperature).

R_fThe value: 0.65 (silica gel, cyclohexane)Ethyl acetate 3:1)

Mass spectrometry (ESI)⁺)：m/z＝271，273[M+H]⁺

Example XLIII

1- (2- {2- [ (ethoxycarbonyl) methylamino)]-phenyl } -2-oxo-ethyl) -3-methyl-7- ((E) -2-butene -1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl]-xanthine

A solution of 110 μ l ethyl diazoacetate in 0.5 ml toluene was added dropwise to 531 mg 1- [2- (2-amino-phenyl) -2-oxo-ethyl ] -3-methyl-7- ((E) -2-buten-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine and 10 mg methyltrioxorhenium (methyltrioxorhenium) in 4.5 ml toluene at ambient temperature under argon. The reaction mixture was stirred at ambient temperature for 15 hours. About 5 mg of methyltrioxorhenium and 20. mu.l of ethyl diazoacetate are then added and the reaction mixture is heated to 50 ℃ for two hours. After cooling to ambient temperature, an additional 5 mg of methyltrioxorhenium and 20. mu.l of ethyl diazoacetate are added. After 16 hours at ambient temperature, the reaction mixture was mixed well with 5 ml of concentrated ammonia and added to the Extrelut package. After 15 minutes, it was rinsed with 200 ml of dichloromethane. The dichloromethane solution was evaporated to dryness 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 theory)

R_fThe value: 0.40 (silica gel, cyclohexane/ethyl acetate ═ 1:1)

Mass spectrometry (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-butoxy) Carbonylamino) -piperidin-1-yl]-xanthine

A mixture of 215 mg of 1- {2- [ 2-cyanomethoxy-phenyl ] -2-oxo-ethyl } -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine and 244 mg of cesium carbonate in 4 ml of N, N-dimethylformamide was stirred at 50 ℃ for two hours and then at 70 ℃ for a further three hours. For workup, the reaction mixture is mixed with water and the precipitate formed is filtered off with suction and dried.

Yield: 130 mg (62% of theory)

Mass spectrometry (ESI)⁺)：m/z＝572[M+H]⁺

Example XLV

1- [2- (3-methyl-2-oxo-2, 3-dihydro-1H-benzimidazol-4-yl) -2-oxo-ethyl]-3-methyl -7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl]-xanthine

Is prepared by treating 1- [2- (1-ethoxycarbonyl-3-methyl-2-oxo-2, 3-dihydro-1H-benzimidazol-4-yl) -2-oxo-ethyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine with a 1N sodium hydroxide solution in methanol at ambient temperature.

R_fThe value: 0.36 (silica gel, ethyl acetate)

Mass spectrometry (ESI)⁺)：m/z＝605[M+H]⁺

Example XLVI

4-acetyl-1-ethoxycarbonyl-1, 3-dihydro-benzimidazol-2-ones

5.29 g of diethyl dicarbonate and 611 mg of dimethylaminopyridine are added to 1.50 g of 1- (2, 3-diamino-phenyl) -ethanone in 75 ml of dichloromethane. The reaction mixture was stirred at ambient temperature for three hours, then 100 mg of dimethylaminopyridine and 1 ml of diethyl dicarbonate were added and the mixture was stirred at ambient temperature for a further 20 hours. For workup, the reaction mixture is diluted with dichloromethane, washed with 2N citric acid solution and with saturated sodium bicarbonate solution and saturated sodium chloride solution, dried over magnesium sulfate and evaporated to dryness. The residue was chromatographed on silica gel using petroleum ether/ethyl acetate (3:1 to 1:2) as eluent. The desired product is stirred with a small amount of tert-butyl methyl ether, filtered off with suction, washed with a small amount of ethyl acetate and tert-butyl methyl ether and dried.

Yield: 900 mg (36% of theory)

R_fThe value: 0.15 (silica gel, petroleum ether/ethyl acetate 2:1)

Mass spectrometry (ESI)⁺)：m/z＝249[M+H]⁺

Example XLVII

1- [ (4-amino-quinazolin-2-yl) methyl group]-3-methyl-7- (2-butyn-1-yl-8- [3- (tert-butoxycarbonyl) Alkylamino) -piperidin-1-yl radical]-xanthine

501 mg of 1-cyanomethyl-3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine were added to a mixture of 17 mg of potassium tert-butoxide in 10 ml of methanol, a clear solution formed after brief heating and stirring, and after about 20 minutes the nitrile had largely reacted to give the imino ester according to thin layer chromatography. 206 mg of 2-amino-benzamidine-hydrochloride are then added and the reaction mixture is refluxed for four hours. After cooling to ambient temperature, the precipitate formed is filtered off with suction, washed with methanol and dried.

Yield: 143 mg (23% of theory)

R_fThe value: 0.15 (silica gel, ethyl acetate)

Mass spectrometry (ESI)⁺)：m/z＝574[M+H]⁺

Example XLVIII

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

150 mg of 1- (2-phenyl-2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine 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 carbon (contaminated with quinoline) were hydrogenated at ambient temperature until the calculated amount of hydrogen had been used up. Then, a spatula tip amount of activated carbon was added and the mixture was filtered with suction. The filtrate was evaporated to dryness and the crude product was purified by chromatography on a silica gel column using cyclohexane/ethyl acetate (7:3 to 4: 6).

Yield: 120 mg (85% of theory)

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

Mass spectrometry (ESI)⁺)：m/z＝537[M+H]⁺

Example XLIX

8-hydroxymethyl-5-methoxy-quinoline

148 mg of sodium hydride (ca 60% in mineral oil) were added portionwise to a solution of 640 mg of 8-hydroxymethyl-quinolin-5-ol in N, N-dimethylformamide while cooling with an ice bath and the reaction mixture was slowly heated to ambient temperature. After gassing had ceased, 230 microliters of methyl iodide were added dropwise with ice bath cooling, and the reaction mixture was then stirred at ambient temperature for an additional about two hours. For the work-up, it is poured onto ice-water, saturated with sodium chloride and extracted with a mixture of diethyl ether and ethyl acetate. The combined extracts were washed with saturated sodium chloride solution, dried over magnesium sulfate, and evaporated to dryness. The residue in the flask was triturated with petroleum ether and the supernatant decanted. The crude product was purified over a silica gel column using ethyl acetate as eluent.

Yield: 470 mg (68% of theory)

R_fThe value: 0.70 (silica gel, ethyl acetate)

Mass spectrometry (ESI)⁺)：m/z＝190[M+H]⁺

The following compounds were obtained in a similar manner to example XLIX:

(1) 8-hydroxymethyl-5-methoxy-isoquinoline

R_fThe value: 0.40 (silica gel, dichloromethane/methanol ═ 10:1)

Mass spectrometry (ESI)⁺)：m/z＝190[M+H]⁺

Example L

8-hydroxymethyl-quinolin-5-ol

3.40 g of quinolin-5-ol are mixed with 8 ml of concentrated hydrochloric acid and 8 ml of 37% formalin solution with cooling in an ice bath. Hydrogen chloride gas was then introduced into the reaction mixture over about two hours while the temperature was slowly increased. The reaction mixture was first stirred overnight with ice bath cooling, then stirred at ambient temperature and then evaporated to dryness in vacuo. The residue in the flask was dissolved in water, covered with a layer of ether and adjusted to pH10 with dilute ammonia solution under cooling in an ice bath and vigorous stirring. After stirring vigorously at ambient temperature for a further two hours, 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 to dryness. The residue in the flask was chromatographed on silica gel column with dichloromethane/methanol (20:1) as eluent.

Yield: 660 mg (16% of theory)

Mass spectrometry (ESI)⁺)：m/z＝176[M+H]⁺

The following compounds are obtained in a similar manner to example L:

(1) 8-hydroxymethyl-isoquinolin-5-ol

R_fThe value: 0.50 (silica gel, dichloromethane/methanol ═ 5:1)

Mass spectrometry (ESI)⁺)：m/z＝176[M+H]⁺

Example LI

1- [ (2-cyclopropyl-quinazolin-4-yl) methyl group ]-3-methyl-7- [ (1-cyclopenten-1-yl) methyl Base of]-8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl]-xanthine

A mixture of 250 mg of 1- (2- {2- [ (cyclopropylcarbonyl) amino ] -phenyl } -2-oxo-ethyl) -3-methyl-7- [ (1-cyclopenten-1-yl) methyl ] -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine and 7.5 ml of ammonia in ethanol (6M) was heated in a bomb vessel at 150 ℃ for seven hours. For workup, the reaction mixture was evaporated to dryness and chromatographed on a silica gel column with dichloromethane/methanol (100:0 to 70:30) as eluent. The contaminated product was partially evaporated to dryness and purified again by reverse phase HPLC column using water/acetonitrile/trifluoroacetic acid (65:15:0.08 to 0:100:0.1) as eluent. The product fractions were evaporated to dryness, made basic with dilute sodium hydroxide solution and extracted with dichloromethane. The combined extracts were dried over magnesium sulfate and evaporated to dryness.

Yield: 40 mg (14% of theory)

R_fThe value: 0.40 (silica gel, dichloromethane/ethyl acetate ═ 1:1)

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

Example LII

4- (2-bromo-acetyl) -1, 3-bis- [ (2-trimethylsilyl-ethoxy) methyl]-1, 3-bis Hydro-benzo Imidazol-2-ones

520 mg of 2-pyrrolidone-hydrobromide and 89 mg of 2-pyrrolidone were added under argon to 420 mg of 4-acetyl-1, 3-bis- [ (2-trimethylsilyl-ethoxy) methyl ] -1, 3-dihydro-benzimidazol-2-one in 5 ml of tetrahydrofuran. The reaction mixture was refluxed for two hours and then filtered with suction while keeping warm. The filter cake was washed with tetrahydrofuran and the filtrate was evaporated to dryness, leaving 660 mg of a tan solid. It is stirred with a small amount of methanol, filtered off with suction, washed with some methanol and dried. The crude product was reacted further without further purification.

Yield: 430 mg (87% of theory)

R_fThe value: 0.23 (silica gel, petroleum ether/ethyl acetate ═ 9:1)

Mass spectrum (EI): 514, 516[ M ] M/z]⁺

The following compounds are obtained in a similar manner to example LII:

(1)7- (2-bromo-acetyl) -1- (tert-butoxycarbonyl) -1H-indole

R_fThe value: 0.33 (silica gel, petroleum ether/ethyl acetate ═ 9:1)

Mass spectrometry (ESI)⁺)：m/z＝338，340[M+H]⁺

(2) 2-bromo-1- (3-isopropyloxy-phenyl) -ethanones

(with phenyltrimethylammonium tribromide in dichloromethane)

R_fThe value: 0.39 (silica gel, cyclohexane/ethyl acetate ═ 9:1)

(3) 2-bromo-1- (3-difluoromethoxy-phenyl) -ethanones

(with phenyltrimethylammonium tribromide in dichloromethane)

R_fThe value: 0.24 (ready-to-use reverse phase TLC plate (e.merck), acetonitrile/water/trifluoroacetic acid 50:50:1)

Example LIII

3-methyl-imidazo [1, 2-a ]]Pyridine-2-carboxylic acid methyl ester

A mixture of 1.91 g 2-aminopyridine and 4.40 g 3-bromo-2-oxo-butyric acid methyl ester in 40 ml ethanol was refluxed for 6 hours and then left at ambient temperature for 2 days. The solvent was distilled off using a rotary evaporator and the crude product was purified by chromatography on a silica gel column using dichloromethane/methanol/ammonia in methanol (95:4:1 to 90:9:1) as eluent. 560 mg of ethyl ester were isolated as a by-product.

Yield: 2.09 g (54% of theory)

R_fThe value: 0.20 (silica gel, dichloromethane/ethyl acetate ═ 1:1)

Mass spectrometry (ESI)⁺)：m/z＝191[M+H]⁺

Example LIV

2-chloromethyl-4-isopropyl-quinazoline

Anhydrous hydrogen chloride gas was introduced into 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, with stirring at ambient temperature, for about five hours. Then, most of the dioxane was distilled off under water jet vacuum. The honey-like residue was mixed with ice water and the resulting suspension was made alkaline with a saturated potassium carbonate solution under ice-bath cooling. The precipitate was filtered off with suction, washed with water and dried. The crude product was purified by chromatography on a silica gel column using petroleum ether/dichloromethane (8:2 to 0:1) as eluent.

Yield: 1.80 g (58% of theory)

R_fThe value: 0.30 (silica gel, dichloromethane/petroleum ether ═ 1:1)

Mass spectrometry (ESI)⁺)：m/z＝221，223[M+H]⁺

Example LV

1-chloromethyl-3-trifluoromethyl-3, 4-dihydro-isoquinoline

530 mg of N- (1-benzyl-2, 2, 2-trifluoro-ethyl) -2-chloro-acetamide (prepared by reacting 1-benzyl-2, 2, 2-trifluoro-ethylamine with chloroacetyl chloride in the presence of triethylamine) and 0.74 ml of phosphorus oxychloride were added to 4.00 g of polyphosphoric acid. The viscous mixture was stirred at 130 ℃ for 1.5 hours. For workup, the reaction mixture was cooled and mixed with ice-water, stirred vigorously for ten minutes and filtered with suction. The filter cake was dissolved in ethyl acetate and the solution was dried over magnesium sulfate and evaporated to dryness leaving a white solid.

Yield: 415 mg (84% of theory)

R_fThe value: 0.55 (aluminum oxide, petroleum ether/ethyl acetate 10:1)

Mass spectrometry (ESI)⁺)：m/z＝248，250[M+H]⁺

The following compounds were obtained in a similar manner to example LV:

(1) 1-methyl-3-trifluoromethyl-3, 4-dihydro-isoquinoline

(the starting material N- (1-benzyl-2, 2, 2-trifluoro-ethyl) -acetamide was obtained by reacting 1-benzyl-2, 2, 2-trifluoro-ethylamine 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 was mixed with a spatula tip of dinitrile 2, 2-azoisobutyrate and refluxed for about six hours. The cooled reaction mixture was filtered and evaporated to dryness. The residue in the flask was allowed to react further without further purification.

R_fThe value: 0.70 (silica gel, cyclohexane/ethyl acetate ═ 3:1)

The following compounds were obtained in a similar manner to example LVI:

(1) 6-bromomethyl-1- [ (2-trimethylsilyl-ethoxy) methyl ] -1H-quinolin-2-one

(2) 1-bromomethyl-4-bromo-3-methoxy-isoquinoline

(3) 2-bromomethyl- [1, 5] naphthyridines

Mass spectrometry (ESI)⁺)：m/z＝233，225[M+H]⁺

(4) 5-bromomethyl- [1, 6- ] naphthyridines

R_fThe value: 0.48 (silica gel, ethyl acetate/methanol 98:2)

(5) 7-bromomethyl-5-phenyl-quinoxalines

R_fThe value: 0.85 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (ESI)⁺)：m/z＝299，301[M+H]⁺

(6) 4-bromomethyl- [1, 5] naphthyridines

R_fThe value: 0.56 (silica gel, dichloromethane/ethyl acetate 7:3)

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

(7) 1-bromomethyl-3-trifluoromethyl-isoquinoline

Mass spectrometry (ESI)⁺)：m/z＝290，292[M+H]⁺

(8) 1-bromomethyl-3-difluoromethyl-isoquinoline

Mass spectrometry (ESI)⁺)：m/z＝272，274[M+H]⁺

(9) 1-bromomethyl-4-chloro-3-methoxy-isoquinoline

Example LVII

1- (1-cyano-1-methyl-ethyl) -3-methyl-isoquinoline

3.30 g of 2, 2-azoisobutyric acid dinitrile are added to 1.60 g of 3-methyl-isoquinoline-N-oxide in 30 ml of toluene. The reaction mixture was stirred at 85 ℃ for six hours and then allowed to stand at ambient temperature for two days. For workup, the reaction mixture was extracted with 20% hydrochloric acid. The combined aqueous phases were diluted with dichloromethane, made basic with saturated potassium carbonate solution under ice bath cooling and extracted with dichloromethane. The combined dichloromethane extracts were dried over magnesium sulfate and evaporated to dryness. The residue was chromatographed on silica gel with cyclohexane as eluent.

Yield: 375 mg (18% of theory)

Mass spectrometry (ESI)⁺)：m/z＝211[M+H]⁺

R_fThe value: 0.75 (silica gel, cyclohexane/ethyl acetate 3:1)

Example LVIII

1- (2-cyanoimino-2-phenyl-ethyl) -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonyl) Alkylamino) -piperidin-1-yl radical]-xanthines (E/Z-mixtures)

0.48 ml of a solution of 1M titanium tetrachloride in dichloromethane was added dropwise to 244 mg of 1- (2-phenyl-2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine in 7 ml of dichloromethane. Then, 88 microliters of 1, 3-bis (trimethylsilyl) carbodiimide was added and the mixture was stirred at ambient temperature for four hours. For workup, the reaction mixture was diluted with dichloromethane and poured onto ice water. The organic phase is washed with 0.5N citric acid, dried over magnesium sulfate and evaporated to dryness. The crude product was purified by chromatography on a silica gel column with dichloromethane/methanol (98:2 to 95:5) as eluent.

Yield: 206 mg (97% of theory)

Mass spectrometry (ESI)⁺)：m/z＝557[M+H]⁺

R_fThe value: 0.16 (silica gel, cyclohexane/ethyl acetate ═ 1:1)

Example LIX

1- [ (1H-benzimidazol-2-yl) methyl group]-3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonyl) Amino) -piperidin-1-yl]-xanthine

350 mg of 1- [ (2-amino-phenylaminocarbonyl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine are refluxed in 3 ml of glacial acetic acid for two hours. The reaction mixture was then evaporated to dryness and the residue in the flask was mixed with 5 ml of 1M sodium hydroxide solution and washed with dichloromethane. The aqueous phase is subsequently acidified with 1M hydrochloric acid and extracted with dichloromethane. The combined extracts were evaporated to dryness and chromatographed on silica gel column with cyclohexane/ethyl acetate/methanol (6:4:0 to 5:4:1) as eluent.

Yield: 250 mg (74% of theory)

Mass spectrometry (ESI)⁺)：m/z＝547[M+H]⁺

Example LX

3, 4-dimethyl-6, 7-dihydro-5H- [2]Pyridine-1-carboxylic acid ethyl ester

Prepared by treating 1.16 g of ethyl 3, 4-dimethyl-4 a- (pyrrolidin-1-yl) -5, 6, 7, 7 a-tetrahydro-4 aH- [2] pyridine-1-carboxylate in 50 ml of dichloromethane with 1.08 g of 70% 3-chloro-perbenzoic acid at ambient temperature.

Yield: 850 mg (97% of theory)

R_fThe value: 0.30 (alumina, petroleum ether/ethyl acetate ═ 5:1)

Mass spectrometry (ESI)⁺)：m/z＝220[M+H]⁺

The following compounds are obtained in a similar manner to example LX:

(1)3, 4-dimethyl-5, 6, 7, 8-tetrahydro-isoquinoline-1-carboxylic acid ethyl ester

R_fThe value: 0.35 (alumina, petroleum ether/ethyl acetate ═ 5:1)

Mass spectrometry (ESI)⁺)：m/z＝234[M+H]⁺

Example LXI

3, 4-dimethyl-4 a- (pyrrolidin-1-yl) -5, 6, 7, 7 a-tetraoxy-4 aH- [2]Pyridine-1-carboxylic ester ethyl ester

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 theory)

R_fThe value: 0.60 (aluminum oxide, petroleum ether/ethyl acetate ═ 5:1)

Mass spectrometry (ESI)⁺)：m/z＝291[M+H]⁺

The following compounds are obtained in a similar manner to example LXI:

(1)3, 4-dimethyl-4 a- (pyrrolidin-1-yl) -4a5, 6, 7, 8, 8 a-hexahydro-isoquinoline-1-carboxylic acid ethyl ester

R_fThe value: 0.60 (alumina, stone)Oleyl ether/ethyl acetate 5:1)

Mass spectrometry (ESI)⁺)：m/z＝305[M+H]⁺

Example LXII

2, 3, 8-trimethyl-quinoxaline-6-carboxylic acid methyl ester

Prepared by reacting 1.60 g of 3, 4-diamino-5-methyl-benzoic acid methyl ester with 0.86 ml of butanedione in a mixture of water and ethanol under reflux.

Yield: 1.53 g (80% of theory)

R_fThe value: 0.63 (silica gel, cyclohexane/ethyl acetate ═ 1:1)

Mass spectrometry (ESI)⁺)：m/z＝231[M+H]⁺

The following compounds are obtained in a similar manner to example LXII:

(1) 8-methyl-quinoxaline-6-carboxylic acid methyl ester

(the reaction is carried out with glyoxal in water).

R_fThe value: 0.55 (silica gel, cyclohexane/ethyl acetate ═ 1:1)

Mass spectrometry (ESI)⁺)：m/z＝203[M+H]⁺

(2) 5-bromo-7-methyl-quinoxaline

(the reaction is carried out with glyoxal in a water/ethanol mixture).

R_fThe value: 0.75 (silica gel, dichloromethane/methanol ═ 95:5)

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

Example LXIII

3, 4-diamino-5-methyl-benzoic acid methyl ester

Prepared by reduction of 3-nitro-4-amino-5-methyl-benzoic acid methyl ester in methanol in the presence of raney nickel at 50psi of hydrogen partial pressure at ambient temperature.

R_fThe value: 0.40 (silica gel, tert-butyl methyl ether)

Example LXIV

3-Nitro-4-amino-5-methyl-benzoic acid methyl ester

Is prepared by treating 3-nitro-4-acetamido-5-methyl-benzoic acid with hydrogen chloride gas in methanol at ambient temperature, followed by heating under reflux.

Mass spectrometry (ESI)⁺)：m/z＝211[M+H]⁺

R_fThe value: 0.75 (silica gel, tert-butyl methyl ether/acetic acid 99:1)

Example LXV

1- (2-phenyl-2-oxo-ethyl) -3-methyl-7- ((E) -1-buten-1-yl) -8-bromo-xanthine

0.13 ml of 35% hydrogen peroxide solution was added to 290 mg of 1- (2-phenyl-2-oxo-ethyl) -3-methyl-7- (1-phenylsulfamoyl-butyl) -8-bromo-xanthine in 6 ml of hexafluoroisopropanol. The reaction mixture was stirred at ambient temperature for one hour, diluted with dichloromethane and washed with sodium thiosulfate solution. The organic phase was dried over magnesium sulfate and evaporated to dryness. The residue in the flask was dissolved in 6 ml of toluene and refluxed for eight hours. The toluene was then distilled off in vacuo and the crude product was purified over a silica gel column with dichloromethane/methanol (100:0 to 95:5) as eluent.

Yield: 104 mg (45% of theory)

R_fThe value: 0.61 (silica gel, dichloromethane/methanol ═ 95:5)

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

The following compounds are obtained in a manner analogous to the example LXV:

(1) 3-methyl-7- (3-methyl-1-buten-1-yl) -8-bromo-xanthine

R_fThe value: 0.24 (silica gel, dichloromethane/methanol ═ 95:5)

Mass spectrometry (ESI)⁺)：m/z＝313，315[M+H]⁺

Example LXVI

1-methanesulfonyloxymethyl-4-difluoromethoxy-naphthalene

Prepared by reacting (4-difluoromethoxy-naphthalen-1-yl) -methanol with methanesulfonyl chloride in dichloromethane in the presence of triethylamine.

The following compounds are obtained in a similar manner to example LXVI:

(1) (E) -1-methanesulfonyloxy-3- (2-nitro-phenyl) -2-propene

(2) (E) -1-Methanesulfonyloxy-3-pentafluorophenyl-2-propene

(3) (E) -1-Methanesulfonyloxy-3- (2-trifluoromethyl-phenyl) -2-propen E

(4) (E) -1-Methanesulfonyloxy-3- (3-trifluoromethyl-phenyl) -2-propen E

(5) (E) -1-Methanesulfonyloxy-3- (4-trifluoromethyl-phenyl) -2-propen E

Example LXVII

7-methyl-5-phenyl-quinoxalines

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 1M aqueous sodium carbonate solution was refluxed for three hours under argon atmosphere. The reaction mixture was then evaporated to dryness and the residue partitioned between ethyl acetate and water. The ethyl acetate phase was separated, dried over magnesium sulfate and evaporated to dryness. The crude product was purified by chromatography on a silica gel column using cyclohexane/ethyl acetate (85:15 to 70:30) as eluent.

Yield: 390 mg (66% of theory)

R_fThe value: 0.36 (silica gel, petroleum ether/ethyl acetate ═ 5:1)

Mass spectrometry (ESI)⁺)：m/z＝221[M+H]⁺

Example LXVIII

1-methyl-3-trifluoromethyl-isoquinoline

Prepared by treating 905 mg of 1-chloromethyl-3-trifluoromethyl-3, 4-dihydro-isoquinoline with 420 mg of potassium tert-butoxide in 10 ml of tetrahydrofuran at ambient temperature.

Yield: 755 mg (98% of theory)

Mass spectrometry (ESI)⁺)：m/z＝212[M+H]⁺

The following compounds are obtained in a similar manner to example LXVIII:

(1) 1-methyl-3-difluoromethyl-isoquinoline

(prepared from 1-methyl-3-trifluoromethyl-3, 4-dihydro-isoquinoline)

Mass spectrometry (ESI)⁺)：m/z＝194[M+H]⁺

Example LXIX

4-chloro-3-methoxy-1-methyl-isoquinoline

Prepared by treating 3-methoxy-1-methyl-isoquinoline with sulfonyl chloride in dichloromethane.

R_fThe value: 0.30 (silica gel, cyclohexane)

Mass spectrometry (ESI)⁺)：m/z＝208，210[M+H]⁺

Example LXX

3-cyclopropyl-8-bromo-xanthine

Prepared by reacting 3-cyclopropyl-xanthine with bromine in the presence of potassium carbonate in acetonitrile at 60 ℃.

R_fThe value: 0.65 (ready-to-use reverse phase TLC plate (e.merck), acetonitrile/water/trifluoroacetic acid 50:50:1)

Mass spectrometry (ESI)⁺)：m/z＝271，273[M+H]⁺

Example LXXI

1, 2, 3, 4-tetrahydro-phenanthridin-6-yl-carboxylic acid ethyl acetate

In analogy to the procedure described by Gonsalves et al (Tetrahedron 1992, 48, 6821), a solution of 3.90 g of ethyl 5, 6, 7, 8-tetrahydro-benzo [1, 2, 4] triazine-3-carboxylate (Sagi et al, Heterocycles1998, 29, 2253) in 20 ml of dioxane was refluxed. Then, in each case, 8.22 g of anthranilic acid and 7.02 g of isoamyl nitrite, each dissolved in 20 ml of dioxane, were added dropwise simultaneously over 25 minutes using two dropping funnels. The reaction mixture was refluxed for an additional 30 minutes. For workup, the cooled dark brown reaction solution is diluted with 150 ml of diethyl ether, washed with 100 ml of 2N sodium hydroxide solution and water, dried over magnesium sulfate and evaporated to dryness. The residue in the brown oily flask was chromatographed over silica gel column using ethyl acetate/petroleum ether (20:80 to 50:50) as eluent. The resulting product was still slightly contaminated, but it was reacted further without further purification.

Yield: 380 mg (8% of theory)

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

Mass spectrometry (ESI)⁺)：m/z＝256[M+H]⁺

Preparation of the final compound:

example 1

1, 3-dimethyl-7- (2, 6-dicyano-benzyl) -8- (3-amino-piperidin-1-yl) -xanthine

129 mg of 3-amino-piperidine-dihydrochloride are 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 was stirred at 80 ℃ for three hours. For workup, the mixture was diluted with dichloromethane and washed with saturated sodium chloride solution. The organic phase was dried over magnesium sulfate and evaporated to dryness. The crude product was purified by chromatography on a silica gel column using dichloromethane/methanol/concentrated ammonia in methanol (95:5:1 to 80:20:1) as eluent.

Yield: 43 mg (14% of theory)

R_fThe value: 0.67 (silica gel, dichloromethane/methanol/concentrated ammonia 80:20:1)

Mass spectrometry (ESI)⁺)：m/z＝419[M+H]⁺

The following compounds are obtained in a similar manner to example 1:

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

R_fThe value: 0.35 (silica gel, dichloromethane/methanol ═ 9:1)

Mass spectrometry (ESI)⁺)：m/z＝433[M+H]⁺

Example 2

1- (2- {2- [ (ethyloxycarbonyl) methoxy group]-phenyl } -2-oxo-ethyl) -3-methyl-7- (3-methyl-2-butane EN-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-butoxycarbonylamino) -piperidin-1-yl ] -xanthine in 4 ml of dichloromethane was mixed with 1 ml of trifluoroacetic acid and stirred at ambient temperature for half an hour. For workup, the reaction mixture was diluted with dichloromethane and washed with saturated potassium carbonate solution. The organic phase was dried, evaporated to dryness and subjected to silica gel column chromatography with dichloromethane/methanol (1:0 to 4:1) as eluent.

Yield: 153 mg (87% of theory)

Mass spectrometry (ESI)⁺)：m/z＝553[M+H]⁺

The following compounds are obtained in a similar manner 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 spectrometry (ESI)⁺)：m/z＝524[M+H]⁺

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

R_fThe value: 0.58 (ready-to-use reverse phase TLC plate (e.merck), acetonitrile/water/trifluoroacetic acid ═ 100:100:0.1)

Mass spectrometry (ESI)⁺)：m/z＝543[M+H]⁺

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

Mass spectrometry (ESI)⁺)：m/z＝465[M+H]⁺

(4)1- (2-phenoxy-ethyl) -3-methyl-7- (2-cyano-benzyl) -8- (3-amino-piperidin-1-yl) -xanthine

R_fThe value: 0.50 (silica gel, dichloromethane/methanol ═ 9:1)

Mass spectrometry (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_fThe value: 0.58 (silica gel, dichloromethane/methanol/concentrated ammonia 80:20:1)

Mass spectrometry (ESI)^-)：m/z＝435[M-H]^-

(6)1- (2- {3- [ (ethoxycarbonyl) methoxy ] -phenyl } -2-oxo-ethyl) -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

Mass spectrometry (ESI)⁺)：m/z＝553[M+H]⁺

(7)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

Mass spectrometry (ESI)⁺)：m/z＝538[M+H]⁺

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

Mass spectrometry (ESI)⁺)：m/z＝552[M+H]⁺

(9)1- (2-methoxy-ethyl) -3-methyl-7- (2-cyano-benzyl) -8- (3-amino-piperidin-1-yl) -xanthine

R_fThe value: 0.40 (silica gel, dichloromethane/methanol ═ 9:1)

Mass spectrometry (ESI)⁺)：m/z＝438[M+H]⁺

(10) 1-methyl-3- [ (methoxycarbonyl) methyl ] -7- (2-cyano-benzyl) -8- (3-amino-piperidin-1-yl) -xanthine

R_fThe value: 0.40 (silica gel, dichloromethane/methanol ═ 9:1)

Mass spectrometry (ESI)⁺)：m/z＝452[M+H]⁺

(11) 1-methyl-3-cyanomethyl-7- (2-cyano-benzyl) -8- (3-amino-piperidin-1-yl) -xanthine

(carried out in dichloromethane with 5-6M hydrochloric acid in isopropanol)

R_fThe value: 0.20 (silica gel, dichloromethane/methanol ═ 9:1)

Mass spectrometry (ESI)⁺)：m/z＝419[M+H]⁺

(12) 1-methyl-3- (2-propyn-1-yl) -7- (2-cyano-benzyl) -8- (3-amino-piperidin-1-yl) -xanthine

R_fThe value: 0.40 (silica gel, dichloromethane/methanol ═ 9:1)

Mass spectrometry (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

R_fThe value: 0.54 (ready-to-use reverse phase TLC plate (e.merck), acetonitrile/water/trifluoroacetic acid ═ 100:100:0.1)

Mass spectrometry (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

R_fThe value: 0.40 (silica gel, dichloromethane)Methanol is 9:1)

Mass spectrometry (ESI)⁺)：m/z＝420[M+H]⁺

(15)1- (2-phenyl-2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

Mass spectrometry (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

R_fThe value: 0.50 (ready-to-use reverse phase TLC plate (e.merck), acetonitrile/water/trifluoroacetic acid ═ 100:100:0.1)

Mass spectrometry (ESI)⁺)：m/z＝522[M+H]⁺

(17) 1-methyl-3-phenyl-7- (2-cyano-benzyl) -8- (3-amino-piperidin-1-yl) -xanthine

R_fThe value: 0.40 (silica gel, dichloromethane/methanol ═ 9:1)

Mass spectrometry (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- ((S) -3-amino-piperidin-1-yl) -xanthine

R_fThe value: 0.50 (ready-to-use reverse phase TLC plate (e.merck), acetonitrile/water/trifluoroacetic acid 50:50:0.1)

Mass spectrometry (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-piperidin-1-yl) -xanthine

R_fThe value: 0.07 (silica gel, dichloromethane/methanol/concentrated ammonia ═ 90:10:1)

Mass spectrometry (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

(carried out in dichloromethane with 5-6M hydrochloric acid in isopropanol)

Mass spectrometry (ESI)⁺)：m/z＝474[M+H]⁺

(21)1- [ (2-oxo-2H-chromen-4-yl) methyl ] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

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

R_fThe value: 0.16 (silica gel, dichloromethane/methanol/concentrated 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-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine)

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

R_fThe value: 0.49 (silica gel, dichloromethane/methanol/concentrated ammonia 90:10:1)

Mass spectrometry (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

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Melting point: 178 ℃ C. 181 ℃ C

Mass spectrometry (ESI)⁺)：m/z＝504[M+H]⁺

(24)1- [ (4-oxo-3, 4-dihydro-2, 3-naphthyridin-1-yl) methyl ] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

R_fThe value: 0.06 (silica gel, dichloromethane/methanol/concentrated ammonia 95:5:0.1)

Mass spectrometry (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

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (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-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

R_fThe value: 0.40 (silica gel, dichloromethane/methanol/concentrated ammonia 90:10:0.1)

Mass spectrometry (ESI)⁺)：m/z＝504[M+H]⁺

(27)1- [ (isoquinolin-3-yl) methyl ] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

R_fThe value: 0.51 (silica gel, two)Methyl chloride/methanol/concentrated ammonia water 90:10:1)

Mass spectrometry (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

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

R_fThe value: 0.23 (silica gel, dichloromethane/methanol/concentrated ammonia 95:5:1)

Mass spectrometry (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-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

R_fThe value: 0.51 (silica gel, dichloromethane/methanol/concentrated ammonia 90:10:1)

Mass spectrometry (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-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

R_fThe value: 0.58 (silica gel, dichloromethane/methanol/concentrated ammonia 90:10:1)

Mass spectrometry (ESI)⁺)：m/z＝500[M+H]⁺

(31)1- [ (3-methyl-4-oxo-3, 4-dihydro-2, 3-naphthyridin-1-yl) methyl ] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine-hydrochloride

(hydrochloric acid isopropanolaminated 5-6M in dichloromethane; precipitation of the product as its hydrochloride salt)

R_fThe value: 0.55 (silica gel, dichloromethane/methanol/concentrated ammonia 90:10:0.1)

Mass spectrometry (ESI)⁺)：m/z＝505[M+H]⁺

(32)1- [2- (3-methylsulfanyl-phenyl) -2-oxo-ethyl ] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

R_fThe value: 0.34 (silica gel, dichloromethane/methanol/concentrated ammonia 90:10:1)

Mass spectrometry (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-piperidin-1-yl) -xanthine

R_fThe value: 0.21 (silica gel, dichloromethane/methanol/concentrated ammonia 90:10:1)

Mass spectrometry (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-piperidin-1-yl) -xanthine

R_fThe value: 0.66 (ready-to-use reverse phase TLC plate (e.merck), acetonitrile/water/trifluoroacetic acid 50:50:1)

Mass spectrometry (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-amino-piperidin-1-yl) -xanthine-hydrochloride

R_fThe value: 0.54 (ready-to-use reverse phase TLC plate (e.merck), acetonitrile/water/trifluoroacetic acid 50:50:1)

Mass spectrometry (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

R_fThe value: 0.47 (ready-to-use reverse phase TLC plate (e.merck), acetonitrile/water/trifluoroacetic acid 50:50:1)

Mass spectrometry (ESI)⁺)：m/z＝509[M+H]⁺

(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

(hydrochloric acid isopropanolaminated 5-6M in dichloromethane; product obtained as its hydrochloride)

R_fThe value: 0.53 (ready-to-use reverse phase TLC plate (e.merck), acetonitrile/water/trifluoroacetic acid 50:50:1)

Mass spectrometry (ESI)⁺)：m/z＝508[M+H]⁺

(38)1- {2- [3- (dimethylaminocarbonyl) -phenyl ] -2-oxo-ethyl } -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine-hydrochloride

Mass spectrometry (ESI)⁺)：m/z＝522[M+H]⁺

(39)1- {2- [3- (morpholin-4-yl-carbonyl) -phenyl ] -2-oxo-ethyl } -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine-hydrochloride

Mass spectrometry (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-amino-piperidin-1-yl) -xanthine-hydrochloride

Mass spectrometry (ESI)⁺)：m/z＝495[M+H]⁺

(41)1- [2- (2-ethoxycarbonyl-phenyl) -2-oxo-ethyl ] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine-hydrochloride

R_fThe value: 0.41 (ready-to-use reverse phase TLC plate (E.Merck), acetonitrile/water/trifluoroacetic acid 50:50:1)

Mass spectrometry (ESI)⁺)：m/z＝523[M+H]⁺

(42)1- {2- [2- (dimethylaminocarbonyl) -phenyl ] -2-oxo-ethyl } -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine-hydrochloride

R_fThe value: 0.53 (ready-to-use reverse phase TLC plate (e.merck), acetonitrile/water/trifluoroacetic acid 50:1)

mass spectrometry (ESI)⁺)：m/z＝522[M+H]⁺

(43)1- {2- [2- (morpholin-4-yl-carbonyl) -phenyl ] -2-oxo-ethyl } -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine-hydrochloride

Mass spectrometry (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

R_fThe value: 0.44 (ready-to-use reverse phase TLC plate (e.merck), acetonitrile/water/trifluoroacetic acid 50:50:1)

Mass spectrometry (ESI)⁺)：m/z＝511[M+H]⁺

(45)1- (2-phenyl-2-oxo-ethyl) -3-methyl-7- (2, 3-dimethyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine-hydrochloride

R_fThe value: 0.68 (ready-to-use reverse phase TLC plate (e.merck), acetonitrile/water/trifluoroacetic acid 50:50:1)

Mass spectrometry (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

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

R_fThe value: 0.38 (silica gel, dichloromethane/methanol/concentrated ammonia 95:5:0.1)

Mass spectrometry (ESI)⁺)：m/z＝449[M+H]+

(47)1- [ (benzo [ b ] thiophen-3-yl) methyl ] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (ESI)⁺)：m/z＝479[M+H]⁺

(48)1- [ (1H-indol-3-yl) methyl ] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

Mass spectrometry (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

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

R_fThe value: 0.30 (silica gel, dichloromethane/methanol/concentrated ammonia 95:5:0.1)

Mass spectrometry (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

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

R_fThe value: 0.56 (silica gel, dichloromethane/methanol/concentrated ammonia 90:10:1)

Mass spectrometry (ESI)⁺)：rm/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

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

R_fThe value: 0.40 (silica gel, dichloromethane/methanol/concentrated ammonia 90:10:1)

Mass spectrometry (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

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

R_fThe value: 0.52 (silica gel, dichloromethane/methanol/concentrated ammonia 90:10:1)

Mass spectrometry (ESI)⁺)：m/z＝458[M+H]⁺

(53)1- (2-cyclohexyl-2-oxo-ethyl) -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (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-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (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

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

R_fThe value: 0.20 (silica gel, dichloromethane/methanol/concentrated ammonia 95:5:0.1)

Mass spectrometry (ESI)⁺)：m/z＝459[M+H]⁺

(56)1- [ (2-methyl-naphthalen-1-yl) methyl ] -3-methyl-7- (2-buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

R_fThe value: 0.25 (silica gel, dichloromethane/methanol/concentrated ammonia 95:5:0.1)

Mass spectrometry (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

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

R_fThe value: 0.43 (silica gel, dichloromethane/methanol/concentrated ammonia 90:10:1)

Mass spectrometry (ESI)⁺)：m/z＝561[M+H]⁺

(58)1- (2-dimethylamino-2-oxo-ethyl) -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

R_fThe value: 0.38 (silica gel, dichloromethane/methanol/concentrated ammonia 90:10:1)

Mass spectrometry (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-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

R_fThe value: 0.35 (silica gel, dichloromethane/methanol/concentrated ammonia 90:10:1)

Mass spectrometry (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-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

R_fThe value: 0.17 (silica gel, dichloromethane/methanol/concentrated ammonia 95:5:0.1)

Mass spectrometry (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

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

R_fThe value: 0.13 (silica gel, dichloromethane/methanol/concentrated ammonia 95:5:0.1)

Mass spectrometry (ESI)⁺)：m/z＝504[M+H]⁺

(62)1- [ (2-methoxy-naphthalen-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (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

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

R_fThe value: 0.42 (silica gel, dichloromethane/methanol/concentrated ammonia 90:10:1)

Mass spectrometry (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

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

R_fThe value: 0.14 (silica gel, dichloromethane/methanol/concentrated ammonia 95:5:0.1)

Mass spectrometry (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

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Melting point: 155 ℃ and 158 DEG C

Mass spectrometry (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

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (ESI)⁺)：m/z＝511[M+H]⁺

(67)1- [ (5-Nitro-naphthalen-1-yl) methyl ] -3-methyl-7- (2-buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

R_fThe value: 0.15 (silica gel, dichloromethane/methanol/concentrated ammonia 95:5:0.1)

Mass spectrometry (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-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (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

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

R_fThe value: 0.46 (silica gel, dichloromethane/methanol/concentrated ammonia 90:10:1)

Mass spectrometry (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

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (ESI)⁺)：m/z＝457[M+H]⁺

(71)1- [ (4-oxo-3, 4-dihydro-quinazolin-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

R_fThe value: 0.38 (silica gel, dichloromethane/methanol/concentrated ammonia 90:10:0.1)

Mass spectrometry (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

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (ESI)⁺)：m/z＝458[M+H]⁺

(73)1- [ (4-dimethylamino-naphthalen-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

R_fThe value: 0.18 (silica gel, dichloromethane/methanol/concentrated ammonia 95:5:0.1)

Mass spectrometry (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

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride; the product still contains about 20% of the Z isomer)

R_fThe value: 0.66 (silica gel, dichloromethane/methanol/concentrated ammonia 90:10:0.1)

Mass spectrometry (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

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (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-buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (ESI)⁺)：m/z＝509[M+H]⁺

(77)1- [ (3-methyl-4-oxo-3, 4-dihydro-quinazolin-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (ESI)⁺)：m/z＝489[M+H]⁺

(78)1- [2- (3-methyl-2-oxo-2, 3-dihydro-benzooxazol-7-yl) -2-oxo-ethyl ] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

R_fThe value: 0.47 (silica gel, dichloromethane/methanol/concentrated ammonia 90:10:1)

Mass spectrometry (ESI)⁺)：m/z＝522[M+H]⁺

(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

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (ESI)⁺)：m/z＝495[M+H]⁺

(80)1- [ (quinazolin-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (ESI)⁺)：m/z＝459[M+H]⁺

(81)1- [ (quinazolin-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((S) -3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (ESI)⁺)：m/z＝459[M+H]⁺

(82)1- [ (quinazolin-2-yl) methyl ] -3-methyl-7- ((E) -2-buten-1-yl) -8- ((S) -3-amino-piperidin-1-yl) -xanthine

R_fThe value: 0.12 (silica gel, dichloromethane/methanol/concentrated ammonia 95:5:0.1)

Mass spectrometry (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-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride; the product still contains about 15% of the Z isomer)

Mass spectrometry (ESI)⁺)：m/z＝461[M+H]⁺

(84)1- [ (3-methyl-isoquinolin-1-yl) methyl ] -3-methyl-7- ((E) -2-buten-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride; the product still contains about 17% of the Z isomer)

R_fThe value: 0.54 (silica gel, dichloromethane/methanol/concentrated ammonia 90:10:1)

Mass spectrometry (ESI)⁺)：m/z＝474[M+H]⁺

(85)1- [ (3-methyl-isoquinolin-1-yl) methyl ] -3-methyl-7- ((E) -2-buten-1-yl) -8- ((S) -3-amino-piperidin-1-yl) -xanthine

Mass spectrometry (ESI)⁺)：m/z＝474[M+H]⁺

(86)1- (2- {2- [ (ethylamino carbonyl) methoxy ] -phenyl } -2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine

Mass spectrometry (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-amino-piperidin-1-yl) -xanthine

Mass spectrometry (ESI)⁺)：m/z＝478[M+H]⁺

(88)1- (2-phenyl-2-oxo-ethyl) -3-methyl-7- [ (1-cyclopenten-1-yl) methyl ] -8- (3-amino-piperidin-1-yl) -xanthine

Mass spectrometry (ESI)⁺)：m/z＝463[M+H]⁺

(89)1- (2- {2- [ (methylaminocarbonyl) methoxy ] -phenyl } -2-oxo-ethyl) -3-methyl-7- [ (1-cyclopenten-1-yl) methyl ] -8- (3-amino-piperidin-1-yl) -xanthine

Mass spectrometry (ESI)⁺)：m/z＝550[M+H]⁺

(90) 1-methyl-3-isopropyl-7- (2-cyano-benzyl) -8- (3-amino-piperidin-1-yl) -xanthine

R_fThe value: 0.40 (silica gel, dichloromethane/methanol ═ 9:1)

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

(91)1- (2- {2- [ (methylaminocarbonyl) methoxy ] -phenyl } -2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

Mass spectrometry (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 spectrometry (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- (3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

R_fThe value: 0.50 (ready-made reverse phase TLC plate (E.Merck), acetonitrileWater/trifluoroacetic acid 50:50:1)

Mass spectrometry (ESI)⁺)：m/z＝505[M+H]⁺

(94)1- (2- {2- [ (isopropylaminocarbonyl) methoxy ] -phenyl } -2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

R_fThe value: 0.30 (silica gel, dichloromethane/methanol ═ 9:1)

Mass spectrometry (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-piperidin-1-yl) -xanthine

Mass spectrometry (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-amino-piperidin-1-yl) -xanthine

(the product contains about 10% of the Z isomer)

Mass spectrometry (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% of the Z isomer)

R_fThe value: 0.30 (silica gel, dichloromethane/methanol ═ 9:1)

Mass spectrometry (ESI)⁺)：m/z＝437[M+H]⁺

(98)1- (2- {2- [ (isopropyloxycarbonyl) methoxy ] -phenyl } -2-oxo-ethyl) ] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

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

(99)1- (2- {2- [ (methylaminocarbonyl) methoxy ] -phenyl } -2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine

Mass spectrometry (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

(product contains about 10% Z-iso shopping)

Mass spectrometry (ESI)⁺)：m/z＝522[M+H]⁺

(101)1- (2- {2- [ (methylaminocarbonyl) methoxy ] -phenyl } -2-oxo-ethyl) -3-methyl-7- ((E) -2-buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

(product contains about 8% Z-iso shopping)

R_fThe value: 0.51 (ready-to-use reverse phase TLC plate (e.merck), acetonitrile/water/trifluoroacetic acid 50:50:0.1)

Mass spectrometry (ESI)⁺)：m/z＝524[M+H]⁺

(102)1- (2- {2- [ (ethylamino carbonyl) methoxy ] -phenyl } -2-oxo-ethyl) -3-methyl-7- (-2-butyn-1-yl) -8- ((S) -3-amino-piperidin-1-yl) -xanthine

Mass spectrometry (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 spectrometry (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-amino-piperidin-1-yl) -xanthine

R_fThe value: 0.54 (ready-to-use reverse phase TLC plate (e.merck), acetonitrile/water/trifluoroacetic acid 50:50:0.1)

Mass spectrometry (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

R_fThe value: 0.48 (ready-to-use reverse phase TLC plate (e.merck), acetonitrile/water/trifluoroacetic acid 50:50:0.1)

Mass spectrometry (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-piperidin-1-yl) -xanthine

Mass spectrometry (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 spectrometry (ESI)⁺)：m/z＝522[M+H]⁺

(108)1- (2-phenyl-2-oxo-ethyl) -3-methyl-7- ((E) -2-buten-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine

(the product contains about 22% of the Z isomer)

Mass spectrometry (ESI)⁺)：m/z＝437[M+H]⁺

(109)1- (2- {2- [ (ethylamino-carbonyl) methoxy ] -phenyl } -2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

R_fThe value: 0.40 (silica gel, dichloromethane/methanol ═ 9:1)

Mass spectrometry (ESI)⁺)：m/z＝536[M+H]⁺

(110)1- [2- (2-acetylamino-phenyl) -2-oxo-ethyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

R_fThe value: 0.23 (silica gel, dichloromethane/methanol/concentrated ammonia 90:10:1)

Mass spectrometry (ESI)⁺)：m/z＝492[M+H]⁺

(111)1- (2- {2- [ 2-oxo-2- (pyrrolidin-1-yl) -ethoxy ] -phenyl } -2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

R_fThe value: 0.20 (silica gel, dichloromethane/methanol ═ 9:1)

Mass spectrometry (ESI)⁺)：m/z＝562[M+H]⁺

(112)1- (2- {2- [ (methylaminocarbonyl) methoxy ] -phenyl } -2-oxo-ethyl) -3-methyl-7- (3-methyl-2-buten-1-yl) -8- ((S) -3-amino-piperidin-1-yl) -xanthine

Mass spectrometry (ESI)⁺)：m/z＝538[M+H]⁺

(113)1- (2-phenyl-2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine

Mass spectrometry (ESI)⁺)：m/z＝435[M+H]⁺

(114)1- (2- {2- [ (ethylamino carbonyl) methoxy ] -phenyl } -2-oxo-ethyl) -3-methyl-7- ((E) -2-buten-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine

(the product contains about 30% of the Z isomer)

Mass spectrometry (ESI)⁺)：m/z＝538[M+H]⁺

(115) 1-methyl-7- (2-cyano-benzyl) -8- (3-amino-piperidin-1-yl) -xanthine

Mass spectrometry (ESI)⁺)：m/z＝380[M+H]⁺

(116)1- (2- {2- [ (isopropylcarbonyl) amino ] -phenyl } -2-oxo-ethyl) -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

R_fThe value: 0.40 (ready-to-use reverse phase TLC plate (e.merck), acetonitrile/water/trifluoroacetic acid 50:50:0.1)

Mass spectrometry (ESI)⁺)：m/z＝536[M+H]⁺

(117)1- (2-phenyl-2-oxo-ethyl) -3-methyl-7- ((E) -2-buten-1-yl) -8- ((S) -3-amino-piperidin-1-yl) -xanthine

(the product contains about 23% of the Z isomer)

R_fThe value: 0.42 (ready-to-use reverse phase TLC plate (e.merck), acetonitrile/water/trifluoroacetic acid 50:50:0.1)

Mass spectrometry (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

R_fThe value: 0.20 (silica gel, dichloromethane/methanol/concentrated ammonia 90:10:1)

Mass spectrometry (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-amino-piperidin-1-yl) -xanthine

R_fThe value: 0.15 (silica gel, dichloromethane/methanol/concentrated ammonia 90:10:1)

Mass spectrometry (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 spectrometry (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

Mass spectrometry (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

R_fThe value: 0.14 (silica gel, dichloromethane/methanol/concentrated ammonia 90:10:1)

Mass spectrometry (ESI)⁺)：m/z＝501，503[M+H]⁺

(123)1- (2- {2- [ (methoxycarbonyl) amino ] -phenyl } -2-oxo-ethyl) -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

Mass spectrometry (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

Mass spectrometry (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

R_fThe value: 0.18 (silica gel, dichloromethane/methanol/concentrated 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 spectrometry (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 spectrometry (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 spectrometry (ESI)⁺)：m/z＝435[M+H]⁺

(129)1- [ (3-methyl-isoquinolin-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((S) -3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Melting point: 155-156.5 DEG C

Mass spectrometry (ESI)⁺)：m/z＝472[M+H]⁺

(130)1- [ (3-methyl-isoquinolin-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (ESI)⁺)：m/z＝472[M+H]⁺

(131)1- [ (4-methyl-isoquinolin-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((S) -3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (ESI)⁺)：m/z＝472[M+H]⁺

(132)1- [ (4-methyl-isoquinolin-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

R_fThe value: 0.46 (silica gel, dichloromethane/methanol/concentrated ammonia: 94:10:1)

Mass spectrometry (ESI)⁺)：m/z＝472[M+H]⁺

(133)1- [ (4-methyl-isoquinolin-1-yl) methyl ] -3-methyl-7- ((E) -2-buten-1-yl) -8- ((S) -3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (ESI)⁺)：m/z＝474[M+H]⁺

(134)1- [ (4-methyl-isoquinolin-1-yl) methyl ] -3-methyl-7- ((E) -2-buten-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Melting point: 167.5-172 deg.C

Mass spectrometry (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- ((R) -amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (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- (S) -3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (ESI)⁺)：m/z＝493[M+H]⁺

(137)1- [ (4-methoxy-naphthalen-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((S) -3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (ESI)⁺)：m/z＝487[M+H]⁺

(138)1- [ (4-methoxy-naphthalen-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (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-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

R_fThe value: 0.41 (silica gel, dichloromethane/methanol/concentrated ammonia 90:10:1)

Mass spectrometry (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- ((S) -3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (ESI)⁺)：m/z＝479[M+H]⁺

(141)1- [ (4-methyl-quinazolin-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3- (S) -amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (ESI)⁺)：m/z＝473[M+H]⁺

(142)1- [ (4-methyl-quinazolin-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3- (R) -amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Melting point: 198-202 deg.C

Mass spectrometry (ESI)⁺)：m/z＝473[M+H]⁺

(143)1- [2- (3-methyl-2-oxo-2, 3-dihydro-benzooxazol-4-yl) -2-oxo-ethyl ] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

R_fThe value: 0.53 (silica gel, dichloromethane/methanol/concentrated ammonia 90:10:1)

Mass spectrometry (ESI)⁺)：m/z＝522[M+H]⁺

(144)1- (2- {2- [ (ethylamino carbonyl) methoxy ] -phenyl } -2-oxo-ethyl) -3-methyl-7- ((E) -2-buten-1-yl) -8- ((S) -3-amino-piperidin-1-yl) -xanthine

Mass spectrometry (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- ((S) -3-amino-piperidin-1-yl) -xanthine

R_fThe value: 0.49 (ready-to-use reverse phase TLC plate (e.merck), acetonitrile/water/trifluoroacetic acid 50:50:0.1)

Mass spectrometry (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- ((R) -3-amino-piperidin-1-yl) -xanthine

Mass spectrometry (ESI)⁺)：m/z＝508[M+H]⁺

(147)1- [2- (2-acetylamino-phenyl) -2-oxo-ethyl) -3-methyl-7- ((E) -2-buten-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine

Mass spectrometry (ESI)⁺)：m/z＝494[M+H]⁺

(148)1- (2- {2- [ (methylaminocarbonyl) methoxy ] -phenyl } -2-oxo-ethyl) -3-methyl-7- ((E) -2-buten-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine

Mass spectrometry (ESI)⁺)：m/z＝524[M+H]⁺

(149)1- [2- (2-acetylamino-phenyl) -2-oxo-ethyl ] -3-methyl-7- ((E) -2-buten-1-yl) -8- ((S) -3-amino-piperidin-1-yl) -xanthine

Mass spectrometry (ESI) ⁺)：m/z＝494[M+H]⁺

(150)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

Mass spectrometry (ESI)⁺)：m/z＝524[M+H]⁺

(151)1- (2- {2- [ (isopropylcarbonyl) amino ] -phenyl } -2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine

Mass spectrometry (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- ((R) -3-amino-piperidin-1-yl) -xanthine

Mass spectrometry (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-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

Mass spectrometry (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- ((S) -3-amino-piperidin-1-yl) -xanthine

Rf value: 0.50 (ready-to-use reverse phase TLC plate (e.merck), acetonitrile/water/trifluoroacetic acid 50:50:0.1)

Mass spectrometry (ESI)⁺)：m/z＝508[M+H]⁺

(155)1- (2- {2- [ (ethylcarbonyl) amino ] -phenyl } -2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine

Mass spectrometry (ESI)⁺)：m/z＝506[M+H]⁺

(156)1- (2- {2- [ (ethylcarbonyl) amino ] -phenyl } -2-oxo-ethyl) -3-methyl-7- (2-butyn-1-yl) -8- ((S) -3-amino-piperidin-1-yl) -xanthine

Mass spectrometry (ESI)⁺)：m/z＝506[M+H]⁺

(157)1- [2- (2-acetylamino-phenyl) -2-oxo-ethyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine

Mass spectrometry (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

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (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

Mass spectrometry (ESI)⁺)：m/z＝556[M+H]⁺

(160)1- [ (2-acetyl-benzofuran-3-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

(obtained as the main product when 1- {2- [2- (2-oxo-propoxy) -phenyl ] -2-oxo-ethyl } -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine is treated with trifluoroacetic acid in dichloromethane)

Mass spectrometry (ESI)⁺)：m/z＝489[M+H]⁺

(161)1- {2- [2- (1-ethoxycarbonyl-1-methyl-ethoxy) -phenyl ] -2-oxo-ethyl } -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

Mass spectrometry (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

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (ESI)⁺)：m/z＝496[M+H]⁺

(163)1- [ (4-dimethylamino-quinazolin-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

R_fThe value: 0.30 (silica gel, dichloromethane/methanol/concentrated ammonia 90:10:0.1)

Mass spectrometry (ESI)⁺)：m/z＝502[M+H]⁺

(164)1- [2- (2-oxo-2, 3-dihydro-benzoxazol-7-yl) -2-oxo-ethyl ] -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

Mass spectrometry (ESI)⁺)：m/z＝508[M+H]⁺

(165)1- (2- {2- [ (ethoxycarbonyl) methylamino ] -phenyl } -2-oxo-ethyl) -3-methyl-7- ((E) -2-buten-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine

Mass spectrometry (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) -xanthine

Mass spectrometry (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) -xanthine

R_fThe value: 0.59 (silica gel, dichloromethane/methanol/concentrated ammonia 80:20:1)

Mass spectrometry (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-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (ESI)⁺)：m/z＝447[M+H]⁺

(169)1- [ (quinoxalin-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (ESI)⁺)：m/z＝459[M+H]⁺

(170)1- [2- (1, 3-dimethyl-2-oxo-2, 3-dihydro-1H-benzimidazol-4-yl) -2-oxo-ethyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (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

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (ESI)⁺)：m/z＝459[M+H]⁺

(172)1- [ (2-cyano-benzofuran-3-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

Mass spectrometry (ESI)⁺)：m/z＝472[M+H]⁺

(173)1- [2- (2-oxo-2, 3-dihydro-benzooxazol-4-yl) -2-oxo-ethyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

Mass spectrometry (ESI)⁺)：m/z＝492[M+H]⁺

(174)1- [ (3-methyl-quinoxalin-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

Melting point: 188.5-191 deg.C

Mass spectrometry (ESI)⁺)：m/z＝473[M+H]⁺

(175)1- [ (3-phenyl-isoquinolin-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

R_fThe value: 0.45 (ready-to-use reverse phase TLC plate (e.merck), acetonitrile/water/trifluoroacetic acid 50:50:1)

Mass spectrometry (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 spectrometry (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

(generated when 1- { [2- (tert-butylcarbonyl) -benzofuran-3-yl ] methyl } -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butoxycarbonylamino) -piperidin-1-yl ] -xanthine was treated with trifluoroacetic acid in dichloromethane)

Mass spectrometry (ESI)⁺)：m/z＝447[M+H]⁺

(178)1- [ (3, 4-methyl-isoquinolin-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine-hydrochloride

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

R_fThe value: 0.75 (aluminum oxide, dichloromethane/methanol ═ 10:1)

Mass spectrometry (ESI)⁺)：m/z＝486[M+H]⁺

(179)1- [ (benzofuran-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine

Mass spectrometry (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-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

R_fThe value: 0.45 (silica gel, dichloromethane/methanol/concentrated ammonia 90:10:0.1)

Mass spectrometry (ESI)⁺)：m/z＝544[M+H]⁺

(181)1- { [4- (piperidin-1-yl) -quinazolin-2-yl ] methyl } -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (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-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

R_fThe value: 0.23 (silica gel, dichloromethane/methanol/concentrated ammonia 90:10:0.1)

Mass spectrometry (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-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

R_fThe value: 0.50 (silica gel, dichloromethane/methanol/concentrated ammonia 90:10:0.1)

Mass spectrometry (ESI)⁺)：m/z＝528[M+H]⁺

(184)1- [2- (3-methyl-2-oxo-2, 3-dihydro-1H-benzimidazol-4-yl) -2-oxo-ethyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (ESI)⁺)：m/z＝505[M+H]⁺

(185)1- [ (4-cyano-naphthalen-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine

Mass spectrometry (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-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

R_fThe value: 0.37 (silica gel, dichloromethane/methanol/concentrated ammonia 90:10:1)

Mass spectrometry (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-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (ESI)⁺)：m/z＝461[M+H]⁺

(188)1- [ (4-amino-quinazolin-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (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 spectrometry (ESI)⁺)：m/z＝437[M+H]⁺

(190)1- [ (8-methoxy-quinolin-5-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine x 2 trifluoroacetic acid

R_fThe value: 0.45 (silica gel, dichloromethane/methanol ═ 5:1)

Mass spectrometry (ESI)⁺)：m/z＝488[M+H]⁺

(191)1- [ (5-methoxy-quinolin-8-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine x trifluoroacetic acid

R_fThe value: 0.20 (silica gel, ethyl acetate/methanol ═ 1:1)

Mass spectrometry (ESI)⁺)：m/z＝488[M+H]⁺

(192)1- [ (4-phenyl-quinazolin-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

R_fThe value: 0.60 (silica gel, dichloromethane/methanol/concentrated ammonia 90:10:1)

Mass spectrometry (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-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (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

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

R_fThe value: 0.55 (ready-to-use reverse phase TLC plate (e.merck), acetonitrile/water/trifluoroacetic acid 50:50:1)

Mass spectrometry (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 spectrometry (ESI)⁺)：m/z＝463[M+H]⁺

(196)1- (2- {2- [ (methylaminocarbonyl) methylamino ] -phenyl } -2-oxo-ethyl) -3-methyl-7- ((E) -2-buten-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine

R_fThe value: 0.52 (ready-to-use reverse phase TLC plate (e.merck), acetonitrile/water/trifluoroacetic acid 50:50:0.1)

Mass spectrum (E)SI⁺)：m/z＝523[M+H]⁺

(197)1- [2- (2-oxo-2, 3-dihydro-1H-benzimidazol-4-yl) -2-oxo-ethyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

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

(198)1- [ (3-difluoromethyl-isoquinolin-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine x trifluoroacetic acid

R_fThe value: 0.75 (silica gel, dichloromethane/methanol ═ 10:1)

Mass spectrometry (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

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

R_fThe value: 0.80 (silica gel, dichloromethane/methanol/concentrated ammonia 96:4:0.5)

Mass spectrometry (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-amino-piperidin-1-yl) -xanthine

R_f-moisture: 0.45 (silica gel, dichloromethane/methanol/concentrated ammonia 90:10:1)

Mass spectrometry (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- ((S) -3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (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-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (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-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Melting point: 176.5-178 deg.C

Mass spectrometry (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-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Melting point: 201 ℃ to 204 DEG C

Mass spectrometry (ESI)⁺)：m/z＝537[M+H]⁺

(205)1- [ (4-isopropyl-quinazolin-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (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-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

R_fThe value: 0.65 (silica gel, dichloromethane/methanol/concentrated ammonia 90:10:1)

Mass spectrometry (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

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (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

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (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-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (ESI)⁺)：m/z＝523[M+H]⁺

(210)1- [ (1H-indol-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine-hydrochloride

Mass spectrometry (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

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (ESI)⁺)：m/z＝485[M+H]⁺

(212)1- [ (5-methoxy-isoquinolin-8-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine x trifluoroacetic acid

R_fThe value: 0.50 (silica gel, dichloromethane/methanol ═ 5:1)

Mass spectrometry (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

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

R_fThe value: 0.25 (ready-to-use reverse phase TLC plate (e.merck), acetonitrile/water/trifluoroacetic acid 50:50:1)

Mass spectrometry (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-trifluoroacetic acid (E/Z-mixture)

Mass spectrometry (ESI)⁺)：m/z＝459[M+H]⁺

(215)1- [ (1H-benzimidazol-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine x trifluoroacetic acid

Mass spectrometry (ESI)⁺)：m/z＝447[M+H]⁺

(216)1- [ (1-methyl-1H-benzimidazol-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

Mass spectrometry (ESI)⁺)：m/z＝461[M+H]⁺

(217)1- [ (4-phenyl-quinazolin-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((R) 3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (ESI)⁺)：m/z＝535[M+H]⁺

(218)1- [ (2, 3-dimethyl-quinoxalin-6-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (ESI)⁺)：m/z＝487[M+H]⁺

(219)1- [ (2-methyl-1H-benzimidazol-5-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

R_fThe value: 0.35(silica gel, dichloromethane/methanol/concentrated ammonia ═ 90:10:0.1)

Mass spectrometry (ESI)⁺)：m/z＝461[M+H]⁺

(220)1- [ (4-phenyl-quinazolin-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((S) -3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (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-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (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-trifluoroacetic acid

R_fThe value: 0.25 (alumina, dichloromethane/methanol ═ 20:1)

Mass spectrometry (ESI)⁺)：m/z＝476[M+H]⁺

(223)1- [ (3, 4-dimethyl-5, 6, 7, 8-tetrahydro-isoquinolin-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine-trifluoroacetic acid

R_fThe value: 0.50 (alumina, dichloromethane/methanol ═ 20:1)

Mass spectrometry (ESI)⁺)：m/z＝490[M+H]⁺

(224)1- [2- (1H-indol-4-yl) -2-oxo-ethyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

Mass spectrometry (ESI)⁺)：m/z＝474[M+H]⁺

(225)1- [ (1H-benzimidazol-5-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

Mass spectrometry (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-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (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

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (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-amino-piperidin-1-yl) -xanthine

Mass spectrometry (ESI)⁺)：m/z＝474[M+H]⁺

(229)1- [ (2, 3, 8-trimethyl-quinoxalin-6-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (ESI)⁺)：m/z＝501[M+H]⁺

(230)1- [ (8-methyl-quinoxalin-6-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (ESI)⁺)：m/z＝473[M+H]⁺

(231)1- [ (4-methyl-2, 3-naphthyridin-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (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-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

R_fThe value: 0.40 (ready-made reverse phase TLC plate (E).Merck), acetonitrile/water/trifluoroacetic acid 50:50:1)

Mass spectrometry (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

Mass spectrometry (ESI)⁺)：m/z＝437[M+H]⁺

(234)1- [ (4-difluoromethoxy-naphthalen-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine

R_fThe value: 0.08 (silica gel, dichloromethane/methanol/concentrated ammonia 95:5:1)

Mass spectrometry (ESI)⁺)：m/z＝523[M+H]⁺

(235)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

Mass spectrometry (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-amino-piperidin-1-yl) -xanthine

Mass spectrometry (ESI)⁺)：m/z＝478[M+H]⁺

(237)1- ((E) -3-pentafluorophenyl-2-propen-1-yl) -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

Mass spectrometry (ESI)⁺)：m/z＝523[M+H]⁺

(238)1- [ (4-Nitro-naphthalen-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine

Mass spectrometry (ESI)⁺)：m/z＝502[M+H]⁺

(239)1- { [1- (2-cyano-ethyl) -1H-benzimidazol-2-yl ] methyl } -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine-hydrochloride

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

R_fThe value: 0.55 (ready-to-use reverse phase TLC plate (e.merck), acetonitrile/water/trifluoroacetic acid 50:50:0.1)

Mass spectrometry (ESI)⁺)：m/z＝500[M+H]⁺

(240)1- ({1- [ (methylaminocarbonyl) methyl ] -1H-benzimidazol-2-yl } methyl) -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine-trifluoroacetic acid

Mass spectrometry (ESI)⁺)：m/z＝518[M+H]⁺

(241)1- [ (1-benzyl-1H-benzimidazol-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

R_fThe value: 0.47 (ready-to-use reverse phase TLC plate (e.merck), acetonitrile/water/trifluoroacetic acid 50:50:0.1)

Mass spectrum (ESI +): 537[ M + H ] M/z]⁺

(242)1- [ (benzoxazol-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine-trifluoroacetic acid

Mass spectrometry (ESI)⁺)：m/z＝448[M+H]⁺

(243)1- [ (5-nitro-benzoxazol-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

Mass spectrometry (ESI)⁺)：m/z＝493[M+H]⁺

(244)1- [ (3-methyl-isoquinolin-1-yl) methyl ] -3-methyl-7- (3-methyl-1-buten-1-yl) -8- ((R-3-amino-piperidin-1-yl) -xanthine

Mass spectrometry (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

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (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

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (ESI)⁺)：m/z＝459[M+H]⁺

(247)1- [ (8-methyl-quinoxalin-6-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((R) 3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (ESI)⁺)：m/z＝473[M+H]⁺

(248)1- [ (2, 3, 8-trimethyl-quinoxalin-6-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((R) 3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (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

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (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

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

R_fThe value: 0.45 (silica gel, dichloromethane/methanol/concentrated ammonia 90:10:1)

Mass spectrometry (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-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (ESI)⁺)：m/z＝475[M+H]⁺

(252)1- [ ([1, 5] naphthyridin-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (ESI)⁺)：m/z＝459[M+H]⁺

(253)1- [2- (3-methyl-2-oxo-2, 3-dihydro-benzooxazol-4-yl) -2-oxo-ethyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Melting point: 187 ℃ C. (189 ℃ C.)

Mass spectrometry (ESI)⁺)：m/z＝506[M+H]⁺

(254)1- [ (8-phenyl-quinoxalin-6-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((R) 3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (ESI)⁺)：m/z＝535[M+H]⁺

(255)1- [ ([1, 5] naphthyridin-4-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

R_fThe value: 0.52 (silica gel, dichloromethane)Alkane/methanol/concentrated ammonia water 90:10:1)

Mass spectrometry (ESI)⁺)：m/z＝459[M+H]⁺

(256)1- ((E) -3-pentafluorophenyl-allyl) -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine

Mass spectrometry (ESI)⁺)：m/z＝523[M+H]⁺

(257)1- [ (E) -3- (2-trifluoromethyl-phenyl) -allyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine

Mass spectrometry (ESI)⁺)：m/z＝501[M+H]⁺

(258)1- [ (E) -3- (3-trifluoromethyl-phenyl) -allyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine

Mass spectrometry (ESI)⁺)：m/z＝501[M+H]⁺

(259)1- [ (E) -3- (4-trifluoromethyl-phenyl) -allyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine

Mass spectrometry (ESI)⁺)：m/z＝501[M+H]⁺

(260)1- [ (3-trifluoromethyl-isoquinolin-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine x trifluoroacetic acid

Mass spectrometry (ESI)⁺)：m/z＝526[M+H]⁺

(261)1- [ (3-methyl-isoquinolin-1-yl) methyl ] -3-isopropyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine

(262)1- [ (3-methyl-isoquinolin-1-yl) methyl ] -3- (4-fluorophenyl) -7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine

(263)1- [ (3-methyl-isoquinolin-1-yl) methyl ] -3-methyl-7- (2-cyano-benzyl) -8- (3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

R_fThe value: 0.51 (ready-to-use reverse phase TLC plate (E.Merck), acetonitrile/water/trifluoroacetic acid 50:1)

Mass spectrometry (ESI)⁺)：m/z＝535[M+H]⁺

(264)1- [ (3-difluoromethyl-isoquinolin-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine

Mass spectrometry (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-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (ESI)⁺)：m/z＝522，524[M+H]⁺

R_fThe value: 0.40 (ready-to-use reverse phase TLC plate (e.merck), acetonitrile/water/trifluoroacetic acid 50:50:1)

(266)1- [ (4-ethoxyquinazolin-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

(by conversion into 1M ethereal hydrochloric acid)

R_fThe value: 0.60 (ready-to-use reverse phase TLC plate (e.merck), acetonitrile/water/trifluoroacetic acid 50:50:1)

Mass spectrometry (ESI)⁺)：m/z＝503[M+H]⁺

(267)1- [ (4-Isopropyloxy-quinazolin-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (ESI)⁺)：m/z＝517[M+H]⁺

(268)1- [ (2-methyl-benzothiazol-6-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Melting point: 167 deg.C

Mass spectrometry (ESI)⁺)：m/z＝478[M+H]⁺

(269)1- [ (3-phenyl-isoquinolin-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (ESI)⁺)：m/z＝534[M+H]⁺

(270)1- [ (4-Phenyloxy-quinazolin-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (ESI)⁺)：m/z＝551[M+H]⁺

(271)1- [ (4-phenyl-quinazolin-2-yl) methyl ] -3-cyclopropyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (ESI)⁺)：m/z＝561[M+H]⁺

(272)1- [ (3-methyl-isoquinolin-1-yl) methyl ] -3-cyclopropyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (ESI)⁺)：m/z＝498[M+H]⁺

(273)1- [ (2-phenyl-quinazolin-4-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

R_fThe value: 0.50 (ready-to-use reverse phase TLC plate (e.merck), acetonitrile/water/trifluoroacetic acid 50:50:1)

Mass spectrometry (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-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (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-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (ESI)⁺)：m/z＝465[M+H]⁺

(276)1- [2- (3-trifluoromethoxy-phenyl) -2-oxo-ethyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (ESI)⁺)：m/z＝519[M+H]⁺

(277)1- [2- (biphenyl-2-yl) -2-oxo-ethyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (ESI)⁺)：m/z＝511[M+H]⁺

(278)1- [2- (biphenyl-3-yl) -2-oxo-ethyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (ESI)⁺)：m/z＝511[M+H]⁺

(279)1- [2- (3-Isopropyloxy-phenyl) -2-oxo-ethyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (ESI)⁺)：m/z＝493[M+H]⁺

(280)1- [ (3-methyl-isoquinolin-1-yl) methyl ] -3-cyclopropyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (ESI)⁺)：m/z＝498[M+H]⁺

(281)1- [ (4-phenyl-quinazolin-2-yl) methyl ] -3-cyclopropyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (ESI)⁺)：m/z＝561[M+H]⁺

(282)1- [ (4-cyano-naphthalen-1-yl) methyl ] -3-cyclopropyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Melting point: 191 deg.C

Mass spectrometry (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-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (ESI)⁺)：m/z＝527[M+H]⁺

(284)1- [2- (3-ethoxyphenyl) -2-oxo-ethyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (ESI)⁺)：m/z＝479[M+H]⁺

(285)1- [2- (3-methoxy-phenyl) -2-oxo-ethyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

R_fThe value: 0.28 (silica gel, dichloromethane/methanol/concentrated ammonia 90:10:1)

Mass spectrometry (ESI)⁺)：m/z＝465[M+H]⁺

(286)1- [2- (2-methoxy-phenyl) -2-oxo-ethyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (ESI)⁺)：m/z＝465[M+H]⁺

(287)1- [ (3-methyl-isoquinolin-1-yl) methyl ] -3-methyl-7- (2-chloro-benzyl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine

Mass spectrometry (ESI)⁺)：m/z＝544，546[M+H]⁺

(288)1- [ (3-methyl-isoquinolin-1-yl) methyl ] -3-methyl-7- (2-bromo-benzyl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine

Mass spectrometry (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-amino-piperidin-1-yl) -xanthine x trifluoroacetic acid

R_fThe value: 0.75 (aluminum oxide, dichloromethane/methanol ═ 10:1)

Mass spectrometry (ESI)⁺)：m/z＝512[M+H]⁺

(290)1- [2- (3-difluoromethoxy-phenyl) -2-oxo-ethyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine

(hydrochloric acid isopropanolaminated 5-6M in methylene chloride)

Mass spectrometry (ESI)⁺)：m/z＝501[M+H]⁺

(291)1- [ (3-methyl-isoquinolin-1-yl) methyl ] -3-methyl-7- (2-ethynyl-benzyl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine

(292)1- [ (3-methyl-isoquinolin-1-yl) methyl ] -3-phenyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine

(293)1- [ (phenanthren-9-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine

(294)1- [ (4-methyl-quinazolin-2-yl) methyl ] -3-methyl-7- (2-chloro-benzyl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine

R_fThe value: 0.35 (silica gel, dichloromethane/methanol/triethylamine ═ 90:10:1)

Mass spectrometry (ESI)⁺)：m/z＝545，547[M+H]⁺

(295)1- [ (4-phenyl-quinazolin-2-yl) methyl ] -3-methyl-7- (2-chloro-benzyl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine

R_fThe value: 0.40 (silica gel, dichloromethane/methanol/triethylamine ═ 90:10:1)

Mass spectrometry (ESI)⁺)：m/z＝607，609[M+H]⁺

Example 3

1- [2- (3-carboxylmethyl-phenyl) -2-oxo-ethyl]-3-methyl-7- (3-methyl-2-butene-1-) Base) -8- (3-amino-piperidin-1-yl) -xanthine

Prepared by saponification of 70 mg of 1- (2- {3- [ (methoxycarbonyl) methoxy ] -phenyl } -2-oxo-ethyl) -3-methyl-7- (3-methyl-2-buten-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine in a mixture of 1 ml of tetrahydrofuran and 0.5 ml of methanol at ambient temperature with 0.10 ml of 4M potassium hydroxide solution.

Yield: 57 mg (84% of theory)

Mass spectrometry (ESI)⁺)：m/z＝525[M+H]⁺

The following compounds are obtained in a similar manner to example 3:

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

(by sodium hydroxide solution)

Mass spectrometry (ESI)^-)：m/z＝523[M-H]^-

Example 4

Coated tablet containing 75 mg of active substance

1 tablet core contains:

75.0 mg of active substance

Calcium phosphate 93.0 mg

Corn starch 35.5 mg

Polyvinylpyrrolidone 10.0 mg

Hydroxypropyl methylcellulose 15.0 mg

Magnesium stearate1.5 mg

230.0 mg

Preparation:

the active substance is mixed with calcium phosphate, corn starch, polyvinylpyrrolidone, hydroxypropylmethylcellulose and half the amount of magnesium stearate specified. Tablets of 13 mm diameter are made in a tablet machine and then, using a suitable machine, are rubbed through a screen having a mesh size of 1.5 mm and mixed with the remaining magnesium stearate. The granules are compressed in a tableting machine to form tablets of the desired shape.

Core weight: 230 mg of

A punch: 9 mm, convex

The tablet cores so produced are coated with a film consisting essentially of hydroxypropylmethylcellulose. The final film coated tablets were polished with beeswax.

Weight of coated tablet: 245 mg of

Example 5

Tablet containing 100 mg of active substance

Consists of the following components:

1 tablet contained:

active substance 100.0 mg

Lactose 80.0 mg

Corn starch 34.0 mg

Polyvinylpyrrolidone 4.0 mg

Magnesium stearate2.0 mg

220.0 mg

The preparation method comprises the following steps:

the active substance, lactose and starch were mixed and uniformly moistened with an aqueous solution of polyvinylpyrrolidone. After the moist composition has been sieved (2.0 mm mesh size) and dried in a shelf dryer at 50 ℃, it is sieved again (1.5 mm mesh size) and the lubricant is added. The final finished mixture is compressed to form tablets.

Tablet weight: 220 mg of

Diameter: 10 mm, biplane, with ground-down sides and a notch on one side.

Example 6

Tablet containing 150 mg of active substance

Consists of the following components:

1 tablet contained:

150.0 mg of active substance

Powdered lactose 89.0 mg

Corn starch 40.0 mg

Colloidal silica 10.0 mg

Polyvinylpyrrolidone 10.0 mg

Magnesium stearate1.0 mg

300.0 mg

Preparation:

the active substance was mixed with lactose, corn starch and silicon dioxide, moistened with a 20% aqueous solution of polyvinylpyrrolidone and passed through a screen having a mesh size of 1.5 mm. The granulate, which had been dried at 45 ℃, was again passed through the same sieve and mixed with the specified amount of magnesium stearate. Tablets were compressed from the mixture.

Tablet weight: 300 mg of

A punch: 10 mm, flat

Example 7

Hard gelatin capsules containing 150 mg of active substance

1 capsule contains:

150.0 mg of active substance

Corn starch (dry) about 80.0 mg

Lactose (as powder) about 87.0 mg

Magnesium stearate3.0 mg

About 420.0 mg

Preparation:

the active substance is mixed with the excipients, passed through a screen having a mesh size of 0.75 mm, and mixed homogeneously using a suitable apparatus. The final mixture was filled into size 1 hard gelatin capsules.

Filling materials of the capsule: about 320 mg

Capsule shell: hard gelatin capsule No. 1

Example 8

Suppository containing 150 mg of active substance

1 suppository contains:

150.0 mg of active substance

1500550.0 mg of polyethylene glycol

6000460.0 mg of polyethylene glycol

Polyoxyethylene sorbitan monostearate 840.0 mg

2,000.0 mg

Preparation:

after melting the suppository base, the active substance is distributed homogeneously therein and the melt is poured into a cooled mold.

Example 9

Suspension containing 50 mg of active substance

100 ml of suspension contained:

active substance 1.00 g

Carboxymethyl cellulose-Na-salt 0.10 g

0.05 g of methyl p-hydroxybenzoate

Propyl p-hydroxybenzoate 0.01 g

10.00 g of cane sugar

Glycerol 5.00 g

20.00 g of 70% sorbitol solution

0.30 g of flavoring agent

Distilled water is added to 100 ml

Preparation:

distilled water was heated to 70 ℃. Methyl and propyl p-hydroxybenzoate, glycerol and sodium carboxymethyl cellulose are dissolved in the solution under stirring, the solution is cooled to ambient temperature, and the active substance is added and uniformly dispersed therein under stirring. After the sugar, sorbitol solution and flavor have been added and dissolved, the suspension is evacuated under stirring to remove air.

5 ml of suspension contain 50 mg of active substance.

Example 10

Ampoule containing 10 mg of active substance

Consists of the following components:

active substance 10.0 mg

Proper amount of 0.01N hydrochloric acid

Double distilled water to 2.0 ml

Preparation:

the active substance was dissolved in the necessary amount of 0.01N HCl, made isotonic with common salt, filter sterilized and transferred to a 2 ml ampoule.

Example 11

Ampoule containing 50 mg of active substance

Consists of the following components:

active substance 50.0 mg

Proper amount of 0.01N hydrochloric acid

Redistilled water to 10.0 ml

Preparation:

the active substance was dissolved in the necessary amount of 0.01N HCl, made isotonic with common salt, filter sterilized and transferred to a 10 ml ampoule.

Claims

1. A compound of the general formula I

Wherein

R¹Represents a 4-methoxy-1-naphthylmethyl group,

2-quinolylmethyl, 4-quinolylmethyl or 6-quinolylmethyl,

2-quinazolinylmethyl, 4-methyl-2-quinazolinylmethyl, or 4-quinazolinylmethyl,

R²represents a methyl group, and

R³represents 2-buten-1-yl or 2-butyn-1-yl,

enantiomers, diastereomers, mixtures thereof, or salts thereof.

2. Compounds of general formula I according to claim 1:

1- [ (4-methoxy-naphthalen-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine,

1- [ (4-methoxy-naphthalen-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((S) -3-amino-piperidin-1-yl) -xanthine,

1- [ (4-methoxy-naphthalen-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine,

enantiomers, diastereomers, mixtures thereof, or salts thereof.

3. Compounds of general formula I according to claim 1:

1- [ (quinolin-4-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine,

1- [ (quinolin-6-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine,

Enantiomers, diastereomers, mixtures thereof, or salts thereof.

4. Compounds of general formula I according to claim 1:

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

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

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

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

1- [ (4-methyl-isoquinolin-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine,

1- [ (4-methyl-isoquinolin-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((S) -3-amino-piperidin-1-yl) -xanthine,

1- [ (4-methyl-isoquinolin-1-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine,

enantiomers, diastereomers, mixtures thereof, or salts thereof.

5. Compounds of general formula I according to claim 1:

1- [ (quinazolin-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine,

1- [ (quinazolin-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- ((S) -3-amino-piperidin-1-yl) -xanthine,

1- [ (quinazolin-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine,

1- [ (4-methyl-quinazolin-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3- (S) -amino-piperidin-1-yl) -xanthine,

1- [ (4-methyl-quinazolin-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3- (R) -amino-piperidin-1-yl) -xanthine,

enantiomers, diastereomers, mixtures thereof, or salts thereof.

6. Compounds of general formula I according to claim 1:

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

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

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

1- [ (4-methyl-isoquinolin-1-yl) methyl ] -3-methyl-7- ((E) -2-buten-1-yl) -8- ((S) -3-amino-piperidin-1-yl) -xanthine,

1- [ (4-methyl-isoquinolin-1-yl) methyl ] -3-methyl-7- ((E) -2-buten-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine,

Enantiomers, diastereomers, mixtures thereof, or salts thereof.

7. Compounds of general formula I according to claim 1:

1- [ (quinazolin-2-yl) methyl ] -3-methyl-7- ((E) -2-buten-1-yl) -8- ((S) -3-amino-piperidin-1-yl) -xanthine,

1- [ (quinazolin-2-yl) methyl ] -3-methyl-7- ((E) -2-buten-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine,

enantiomers, diastereomers, mixtures thereof, or salts thereof.

8. A compound of the general formula I according to claim 1,

wherein

R¹Represents 4-methyl-2-quinazolinylmethyl,

R²represents a methyl group, and

R³represents a 2-butyn-1-yl group,

or a salt thereof.

9. Compounds of general formula I according to claim 5 or 8:

1- [ (4-methyl-quinazolin-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3- (R) -amino-piperidin-1-yl) -xanthine, or a salt thereof.

10. Compounds of general formula I according to claim 9:

1- [ (4-methyl-quinazolin-2-yl) methyl ] -3-methyl-7- (2-butyn-1-yl) -8- (3- (R) -amino-piperidin-1-yl) -xanthine.

11. Physiologically acceptable salts of compounds according to any of claims 1 to 10 with inorganic or organic acids or bases.

12. Physiologically acceptable salts of the compounds according to claim 9 with inorganic or organic acids.

13. A pharmaceutical composition comprising a compound according to any one of claims 1 to 10, or a physiologically acceptable salt according to claim 11 or 12, optionally together with one or more inert carriers and/or diluents.

14. A pharmaceutical composition comprising a compound according to claim 9, or a physiologically acceptable salt according to claim 12, optionally together with one or more inert carriers and/or diluents.

15. A pharmaceutical composition comprising a compound according to claim 10, optionally together with one or more inert carriers and/or diluents.

16. Use of a compound according to any one of claims 1 to 12 for the preparation of a pharmaceutical composition for the treatment of type I and type II diabetes, arthritis, obesity, allograft transplantation and calcitonin induced osteoporosis.

17. Use of a compound according to any one of claims 9, 10 and 12 for the preparation of a pharmaceutical composition for the treatment of type II diabetes or obesity.

18. Use of a compound according to claim 10 for the preparation of a pharmaceutical composition for the treatment of type II diabetes.

19. A process for the preparation of a pharmaceutical composition according to any one of claims 13 to 15, characterized in that a compound according to any one of claims 1 to 12 is incorporated by non-chemical means into one or more inert carriers and/or diluents.

20. A process for the preparation of a pharmaceutical composition according to claim 14, characterized in that a compound according to claim 9 or 12 is incorporated into one or more inert carriers and/or diluents.

21. A process for the preparation of a pharmaceutical composition according to claim 15, characterized in that a compound according to claim 10 is incorporated into one or more inert carriers and/or diluents.

22. A process for the preparation of compounds of the general formula I according to any one of claims 1 to 12, characterized in that

a) Reacting a compound of formula (II) with 3-aminopiperidine, an enantiomer or a salt thereof,

in the formula (II)

R¹To R³Is as defined in claim 1 or 8, and

Z¹represents a leaving group, or

b) Deprotection of the compound of formula (III)

Wherein R is¹、R²And R³Is as defined in claim 1 or 8, and/or

Followed by, if desired, cleaving any protecting groups used during the reaction, and/or

Separating the compound of the general formula I thus obtained into its enantiomers or diastereomers, and/or

The compound of formula I thus obtained is converted into its salt with an inorganic or organic acid or base.

23. A process for the preparation of compounds of the general formula I according to claim 9, characterized in that

a) Reacting a compound of the general formula (II) with (R) -3-aminopiperidine or a salt thereof,

wherein

R¹Represents 4-methyl-2-quinazolinylmethyl,

R²represents a methyl group, and

R³represents but-2-yn-1-yl, and

Z¹represents a leaving group, or

b) Deprotection of the compound of formula (IIIa)

Wherein

R¹Represents 4-methyl-2-quinazolinylmethyl,

R²represents a methyl group, and

R³represents but-2-yn-1-yl, and/or

24. A method according to claim 22 or 23, wherein Z is¹Represents a halogen atom, a substituted hydroxy group, a mercapto group, a sulfinyl groupA group, sulfonyl group or sulfonyloxy group.

25. The process according to any one of claims 22 to 24, wherein the compound of formula I obtained is converted into a physiologically acceptable salt.

26. A compound according to claim 8 which is

Or a physiologically acceptable salt thereof.