CA2435730C - Xanthine derivatives, the preparation thereof and their use as pharmaceutical compositions - Google Patents

Xanthine derivatives, the preparation thereof and their use as pharmaceutical compositions Download PDF

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CA2435730C
CA2435730C CA2435730A CA2435730A CA2435730C CA 2435730 C CA2435730 C CA 2435730C CA 2435730 A CA2435730 A CA 2435730A CA 2435730 A CA2435730 A CA 2435730A CA 2435730 C CA2435730 C CA 2435730C
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group
alkyl
methyl
substituted
amino
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CA2435730A1 (en
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Frank Himmelsbach
Michael Mark
Matthias Eckhardt
Elke Langkopf
Roland Maier
Ralf Lotz
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Boehringer Ingelheim Pharma GmbH and Co KG
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Priority claimed from DE2001109021 external-priority patent/DE10109021A1/en
Priority claimed from DE2001117803 external-priority patent/DE10117803A1/en
Priority claimed from DE10140345A external-priority patent/DE10140345A1/en
Priority claimed from DE2002103486 external-priority patent/DE10203486A1/en
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    • C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
    • C07D473/06—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3
    • C07D473/08—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3 with methyl radicals in positions 1 and 3, e.g. theophylline
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    • C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
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    • C07D473/10—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3 with methyl radicals in positions 3 and 7, e.g. theobromine
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    • C07D473/12—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3 with methyl radicals in positions 1, 3, and 7, e.g. caffeine

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Abstract

The present invention relates to substituted xanthines of general formula (see formula I) wherein R1 is, for example, H, optionally substituted alkyl, alkenyl, alkynyl, an aryl or a heterocylic group; R 2 is, for example, H, an optionally substituted alkyl or alkenyl, alkynyl cycloalkyl, an aryl or a heterocyclic group; R3 is, for example, optionally substituted alkyl, optionally substituted alkenyl, alkynyl, or aryl; and R4 is a substituted heterocyclic group; the tautomers and the stereoisomers thereof, mixtures thereof, the prodrugs and the salts thereof which have valuable pharmacological properties, particularly an inhibiting effect on the activity of the enzyme dipeptidylpeptidase-IV (DPP-IV).

Description

DEMANDES OU BREVETS VOLUMINEUX
LA PRESENTE PARTIE DE CETTE DEMANDE OU CE BREVETS
COMPREND PLUS D'UN TOME.
CECI EST LE TOME DE _2 NOTE: Pour les tomes additionels, veillez contacter le Bureau Canadien des Brevets.

JUMBO APPLICATIONS / PATENTS

THIS SECTION OF THE APPLICATION / PATENT CONTAINS MORE
THAN ONE VOLUME.

NOTE: For additional volumes please contact the Canadian Patent Office.

75092pct.206 Boehringer Ingelheim Pharma KG Case 5/1315-EG
D-55216 Ingelheim/Rhein PCT text Xanthine derivatives, the preparation thereof and their use as pharmaceutical compositions The present invention relates to substituted xanthines of general formula I

RN N
I />- R4 O N N
I

the tautomers, the stereoisomers, the mixtures thereof and the salts thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases which have valuable pharmacological properties, particularly an inhibiting effect on the activity of the enzyme dipeptidylpeptidase-IV (DPP-IV), the preparation thereof, the use thereof for preventing or treating illnesses or conditions connected with an increased DPP-IV activity or capable of being prevented or alleviated by reducing the DPP-lV activity, particularly type I or type II
diabetes mellitus, the pharmaceutical compositions containing a compound of general formula (I) or a physiologically acceptable salt thereof and processes for the preparation thereof.

In the above formula I

R1 denotes a hydrogen atom, a C1.8-alkyl group, a C3_8-alkenyl group, a C3-4-alkenyl group which is substituted by a C1.2-alkyloxy-carbonyl, aminocarbonyl, C1_3-alkylamino-carbonyl, di-(C1.3-alkyl)-amino-carbonyl, pyrrolidin-l-ylcarbonyl, piperidin-1-ylcarbonyl or morpholin-4-ylcarbonyl- group, a C3_8-alkynyl group, I
a C1_6-alkyl group substituted by a group Ra, wherein Ra denotes a C3_7-cycloalkyl, heteroaryl, cyano, carboxy, C1_3-alkyloxy-carbonyl, aminocarbonyl, C1_3-alkylamino-carbonyl, di-(C,.3-alkyl)-amino-carbonyl, pyrrolidin-l-ylcarbonyl, piperidin-l-ylcarbonyl, morpholin-4-ylcarbonyl, piperazin-1 -ylcarbonyl, 4-methylpiperazin-1 -ylcarbonyl or 4-ethylpiperazin-1-ylcarbonyl group, a C1.6-alkyl group substituted by a phenyl group, wherein the phenyl ring is substituted by the groups R10 to R14 and R10 denotes a hydrogen atom, a fluorine, chlorine, bromine or iodine atom, a C1-4-alkyl, hydroxy, or C1..a-alkyloxy group, a nitro, amino, C1_3-alkylamino, di-(C1.3-alkyl)amino, cyano-Cl-3-alkylamino, [N-(cyano-C1.3-alkyl)-N-C1.3-alkyl-amino], C1.3-alkyloxy-carbonyl-C1.3-alkylamino, pyrrolidin-1-yl, piperidin-1-yl, morpholin-4-yl, piperazin-1-yl or4-(C1.3-al kyl)-piperazin-1-yl group, a C,.3-alkyl-carbonylamino, arylcarbonylamino, aryl-C,.3-alkyl-carbonylamino, C,.3-alkyloxy-carbonylamino, aminocarbonylamino, C,-3-alkyl-aminocarbonyl-amino, di-(C,.3-alkyl)aminocarbonylamino, pyrrolidin-1-yl-carbonylamino, piperidin-1-yl-carbonylamino, morpholin-4-yl-carbonylamino, piperazin-l -yl-carbonylamino or 4-(C,.3-alkyl)-piperazin-1-yl-carbonylamino, C,-alkyl-sulphonylamino, bis-(C,_3-alkylsulphonyl)-amino, aminosuiphonylamino, C1.3-alkylamino-sulphonylamino, di-(C,.3-alkyl)amino-sulphonylamino, pyrrolidin-1-yl-sulphonylamino, piperidin-1-yl-sulphonylamino, morpholin-4-yl-sulphonylamino, piperazin-l-yl-sulphonylamino or 4-(C,.3-alkyl)-piperazin-1-yl-sulphony lamino, (C,.3-alkylamino)thiocarbonylamino, (C,.3-alkyloxy-carbonylamino)carbonylamino, arylsulphonylamino or aryl-C,.3-alkyl-suiphonylamino group, an N-(C,.3-alkyl)-C,_3-alkyl-carbonylamino, N-(C,.3-alkyl)-arylcarbonylamino, N-(C,.3-alkyl)-aryl-C,.3-alkyl-carbonylamino, N-(C,.3-alkyl)-C,_3-alkyloxy-carbonyl-amino, N-(aminocarbonyl)-C,.3-alkylamino, N-(C,.3-alkyl-aminocarbonyl)-C,.3-alkylamino, N-[di-(C,.3-alkyl)aminocarbonyl]-C1.3-alkylamino, N-(C,.3-alkyl)-C1.3-alkyl-sulphonylamino, N-(C,.3-alkyl)-arylsulphonylamino or N-(C,.3-alkyl)-aryl-C1_3-alkyl-sulphonylamino group, a 2-oxo-imidazolidin-1-yl, 2,4-dioxo-imidazolidin-1 -yl, 2,5-dioxo-imidazolidin- 1 -yl or 2-oxo-hexahydropyrimidin-1 -yl group wherein the nitrogen atom in the 3 position in each case may be substituted by a methyl or ethyl group, a cyano, carboxy, C,.3-alkyloxy-carbonyl, aminocarbonyl, C,_3-alkyl-aminocarbonyl, di-(C,.3-alkyl)-aminocarbonyl, pyrrolidin-1-yl-carbonyl, piperidin-1 -yl-carbonyl, morpholin-4-yl-carbonyl, piperazin-1-yl-carbonyl or 4-(C,.3-alkyl)-piperazin-1-yl-carbonyl group, a C,_3-alkyl-carbonyl or an arylcarbonyl group, a carboxy-C,.3-alkyl, C,.3-alkyloxy-carbonyl-C,.3-alkyl, cyano-C,.3-alkyl, aminocarbonyl-C1-3-alkyl, C1.3-alkyl-aminocarbonyl-C1.3-alkyl, di-(C, -alkyl)-aminocarbonyl-C,_3-alkyl, pyrrolidin-l -yl-carbonyl-C,.3-alkyl, piperidin-1-yl-carbonyl-C,_3-alkyl, morpholin-4-yl-carbonyl-C1.3-alkyl, piperazin-1-yl-carbonyl-C,.3-alkyl or 4-(C1.3-alkyl)-piperazin-1-yl-carbonyl-C,_3-alkyl group, a carboxy-C1.3-alkyloxy, C,_3-alkyloxy-carbonyl-C1.3-alkyloxy, cyano-C,_3-alkyloxy, aminocarbonyl-Cl.3-alkyloxy, C,_3-alkyl-aminocarbonyl-C1.3-alkyloxy, di-(C1.3-alkyl)-aminocarbonyl-C,-3-alkyloxy, pyrrolidin-1-yl-carbonyl-C,.3-alkyl-oxy, piperidin-1-yl-carbonyl-C1.3-alkyloxy, morpholin-4-yl-carbonyl-C1.3-alkyl-oxy, piperazin-l -yl-carbonyl-C,_3-alkyloxy or 4-(C1.3-alkyl)-piperazin-l -yl-carbonyl-C,_3-alkyloxy group, a hydroxy-Cl-3-alkyl, C,.3-alkyloxy-C,.3-alkyl, amino-C1.3-alkyl, C,_3-alkylamino-C1.3-alkyl, di-(C1_3-alkyl)-amino-C,_3-alkyl, pyrrolidin-1-yI-C1.3-alkyl, piperidin-1 -yl-C,_3-alkyl, morpholin-4-yI-C,.3-alkyl, piperazin-l-yl-C1.3-alkyl, 4-(C1.3-alkyl)-piperazin-1-yI-C,_3-alkyl group, a hydroxy-C,.3-alkyloxy, C,_3-alkyloxy-Cl-3-alkyloxy, C1_3-alkylsulphanyl-C,_3-alkyloxy, C,_3-alkylsulphinyl-C1.3-alkyloxy, C1_3-alkylsulphonyl-C,.3-alkyloxy, amino-C1.3-alkyloxy, C,_3-alkylamino-C1.3-alkyloxy, di-(C1.3-alkyl)-amino-C,_3-alkyloxy, pyrrolidin-1-yI-C1_3-alkyloxy, piperidin-1-yI-C13-alkyloxy, morpholin-4-yl-C,_3-alkyloxy, piperazin-1-yI-C,_3-alkyloxy, 4-(C,.3-alkyl)-piperazin-1-yI-C,.3-alkyloxy group, a mercapto, C1.3-alkylsulphanyl, C,.3-alkysulphinyl, C,-3-alkylsulphonyl, C1.3-alkylsulphonyloxy, arylsulphonyloxy,.trifluoromethylsulphanyl, trifluoromethylsulphinyl or trifluoromethylsulphonyl group, a suipho, aminosuiphonyl, C,_3-alkyl-aminosulphonyl, di-(C1.3-alkyl)-amino-sulphonyl, pyrrolidin-1-yl-suiphonyl, piperidin-1-yl-sulphonyl, morpholin-4-yi-sulphonyl, piperazin-1-yl-sulphonyl or 4-(C1-3-alkyl)-piperazin-1-yl-suiphonyl group, a methyl or methoxy group substituted by 1 to 3 fluorine atoms, an ethyl or ethoxy group substituted by 1 to 5 fluorine atoms, a C2.4-alkenyl or C2.4-alkynyl group, a C3.4-alkenyloxy or C3-4-alkynyloxy group, a Cis-cycloalkyl or C3.6-cycloalkyloxy group, a C3_6-cycloalkyl-C1.3-alkyl or C3.6-cycloalkyl-C,_3-alkyloxy group or an aryl, aryloxy, aryl-C1.3-alkyl or aryl-C1.3-alkyloxy group, R" and R12, which may be identical or different, each denote a hydrogen atom, a fluorine, chlorine, bromine or iodine atom, a C1.3-alkyl, trifluoromethyl, hydroxy or C1.3-alkyloxy group or a cyano group, or R11 together with R12, if they are bound to adjacent carbon atoms, also denote a methylenedioxy, difluoromethylenedioxy or a straight-chain C3.5-alkylene group, and R13 and R14, which may be identical or different, each denote a hydrogen atom, a fluorine, chlorine or bromine atom, a trifluoromethyl, C1.3-alkyl or C1.3-alkyloxy group, a phenyl-C1.4-alkyl group wherein the alkyl moiety is substituted by a cyano, carboxy, Cis-alkyloxy-carbonyl, aminocarbonyl, C1_3-alkyl-aminocarbonyl, di-(C1.3-alkyl)-aminocarbonyl, pyrrolidin-1-yl-carbonyl, piperidin-1-yl-carbonyl, morpholin-4-yl-carbonyl group and the phenyl moiety is substituted by the groups R1 to R14, wherein R10 to R14 are as hereinbefore defined, a phenyl group substituted by the groups R10 to R14, wherein R10 to R14 are as hereinbefore defined, a phenyl-C2.3-alkenyl group wherein the phenyl moiety is substituted by the groups R10 to R14, wherein R10 to R14 are as hereinbefore defined, a phenyl-(CH2)m-A-(CH2)n-group wherein the phenyl moiety is substituted by R10 to R14, wherein R10 to R14 are as hereinbefore defined and A denotes a carbonyl, cyanoiminomethylene, hydroxyiminomethylene or C1.3-alkyloxyiminomethylene group, m denotes the number 0, 1 or 2 and n denotes the number 1, 2 or 3, a phenylcarbonylmethyl group wherein the phenyl moiety is substituted by R10 to R14, wherein R10 to R14 are as hereinbefore defined and the methyl moiety is substituted by a C1_3-alkyl group, a phenyl-(CH2)m B-(CH2)õ group wherein the phenyl moiety is substituted by R10 to A14, wherein R10 to R14, m and n are as hereinbefore defined and B denotes a methylene group which is substituted by a hydroxy, C1.3-alkyloxy, amino, C1.3-alkylamino, di-(C1.3-alkyl)-amino, mercapto, C1.3-alkylsulphanyl, C1.3-alkylsulphinyl or C1_3-alkylsulphonyl group and is optionally additionally substituted by a methyl or ethyl group, a naphthyl-C1.3-alkyl group wherein the naphthyl moiety is substituted by the groups R10 to R14, wherein R10 to R'4 are as hereinbefore defined, a naphthyl-(CH2),,,-A-(CH2)n group wherein the naphthyl moiety is substituted by R10 to R14, wherein R10 to R14, A, m and n are as hereinbefore defined, a naphthyl-(CH2)m-B-(CH2)n group wherein the naphthyl moiety is substituted by to R14, wherein R10 to R14, B, m and n are as hereinbefore defined, a [1,4]naphthoquinon-2-yl, chromen-4-on-3-yi, 1-oxoindan-2-yl, 1,3-dioxoindan-2-yi-or 2,3-dihydro-3-oxo-benzofuran-2-yl group a heteroaryl-(CH2)m-A-(CH2)n group, wherein A, m and n are as hereinbefore defined, a heteroaryl-(CH2)m-B-(CH2)n group, wherein B, m and n are as hereinbefore defined, a C1.6-alkyl-A-(CH2)n group, wherein A and n are as hereinbefore defined, a C3_,-cycloalkyl-(CH2)m A-(CH2)n group, wherein A, m and n are as hereinbefore defined, a C3.,-cycloalkyl-(CH2)m B-(CH2)n group, wherein B, m and n are as hereinbefore defined, an R21-A-(CH2)n group wherein R21 denotes a C1.3-alkyloxycarbonyl, aminocarbonyl, C1.3-alkylaminocarbonyl, di-(C1.3-al kyl)aminocarbonyl, pyrrolidin-1 -yl-carbonyl, piperidin-1-yl-carbonyl or morpholin-4-yl-carbonyl, piperazin-1-yl-carbonyl, 4-methylpiperazin-1-yl-carbonyl or 4-ethylpiperazin-1-yl-carbonyl group and A
and n are as hereinbefore defined, a phenyl-(CH2)m-D-C1.3-alkyl group wherein the phenyl moiety is substituted by the groups R10 to R14, wherein R10 to R14 and m are as hereinbefore defined and D
denotes an oxygen or sulphur atom, an imino, C1.3-alkylimino, sulphinyl or suiphonyl group, a naphthyl-(CH2)m-D-C1.3-alkyl group wherein the naphthyl moiety is substituted by the groups R10 to R14, wherein R10 to R14, D and m are as hereinbefore defined, a C2-6-alkyl group substituted by a group Rb, wherein Rb is isolated by at least two carbon atoms from the cyclic nitrogen atom in the 1 position of the xanthine skeleton and Rb denotes a hydroxy, C1.3-alkyloxy, mercapto, C1.3-alkylsulphanyl, C1-3-alkylsulphinyl, C1.3-alkylsulphonyl, amino, C1.3-alkylamino, di-(C1.3-alkyl)-amino, pyrrolidin-1-yl, piperidin-1-yl, morpholin-4-yl, piperazin-1-yl or4-(C1.3-alkyl)-piperazin-1-yl group, a C3_6-cycloalkyl group, or an amino or arylcarbonylamino group, R2 denotes a hydrogen atom, a C1.8-alkyl group, a C2.6-alkenyl group, a C3_6-alkynyl group, a C1.6-alkyl group substituted by a group Ra, wherein Ra is as hereinbefore defined, a tetrahydrofuran-3-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, tetrahydrofuranyl-C1.3-alkyl or tetrahydropyranyl-C1.3-alkyl group, a C1.6-alkyl group substituted by a phenyl group, wherein the phenyl ring is substituted by the groups R10 to R14 and R10 to R14 are as hereinbefore defined, a phenyl group substituted by the groups R10 to R14, wherein R10 to R'4 are as hereinbefore defined, a phenyl-C2.3-alkenyl group wherein the phenyl moiety is substituted by the groups R10 to R14, wherein R10 to R14 are as hereinbefore defined, a phenyl-(CH2)m A-(CH2)ngroup wherein the phenyl moiety is substituted by R10 to R14, wherein R10 to R14, A, m and n are as hereinbefore defined, a phenyl-(CH2)m-B-(CH2)õ group wherein the phenyl moiety is substituted by R10 to R74, wherein R10 to R14, B, m and n are as hereinbefore defined, a heteroaryl-(CH2)m A-(CH2)ngroup, wherein A, m and n are as hereinbefore defined, a heteroaryl-(CH2)m-B-(CH2)n group, wherein B, m and n are as hereinbefore defined, a C1_6-alkyl-A-(CH2)õ group, wherein A and n are as hereinbefore defined, a C3_7-cycloalkyl-(CH2)m-A-(CH2)n group, wherein A, m and n are as hereinbefore defined, a C3.7-cycloalkyl-(CH2)m-B-(CH2)ngroup, wherein B, m and n are as hereinbefore defined, an R21-A-(CH2)n group wherein R21, A and n are as hereinbefore defined, a phenyl-(CH2)m-D-C1.3-alkyl group wherein the phenyl moiety is substituted by the groups R10 to R14, wherein R10 to R14, m and D are as hereinbefore defined, a C2.6-alkyl group substituted by a group Rb, wherein Rb is isolated by at least two carbon atoms from the cyclic nitrogen atom in the 3 position of the xanthine skeleton and is as hereinbefore defined, or a C3.6-cycloalkyl group, R3 denotes a C1.8-alkyl group, a C1.4-alkyl group substituted by the group R0, wherein Rc denotes a C3.7-cycloalkyl group optionally substituted by one or two C1.3-alkyl groups, a C5.7-cycloalkenyl group optionally substituted by one or two C1.3-alkyl groups, an aryl group, or a furanyl, thienyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyridyl, pyridazinyl, pyrimidyl or pyrazinyl group, wherein the abovementioned heterocyclic groups may each be substituted by one or two C1.3-alkyl groups or by a fluorine, chlorine, bromine or iodine atom or by a trifluoromethyl, cyano or C1.3-alkyloxy group, a C3.8-alkenyl group, a C3.6-alkenyl group substituted by a fluorine, chlorine or bromine atom or a trifluoromethyl group, a C3.8-alkynyl group, an aryl group or an aryl-C2.4-alkenyl group, and R4 denotes an azetidin-1-yl or pyrrolidin-1-yl group which is substituted in the 3 position by an R NRd group and may additionally be substituted by one or two C1.3-alkyl groups, wherein R. denotes a hydrogen atom or a C1.3-alkyl group and Rd denotes a hydrogen atom, a C1.3-alkyl group, an Rf-C,.3-alkyl group or an Rg-C2.3-alkyl group, wherein Rf denotes a carboxy, C1.3-alkyloxy-carbonyl, aminocarbonyl, C1.3-alkyl-amino-carbonyl, di-(C1.3-alkyl)-aminocarbonyl, pyrrolidin-1-yl-carbonyl, 2-cyanopyrrolidin-1 -yl-carbonyl, 2-carboxypyrrolidin-1-yl-carbonyl, 2-methoxycarbonylpyrrolidin-1-yl-carbonyl, 2-ethoxycarbonylpyrrolidin-1-yl-carbonyl, 2-aminocarbonylpyrrolidin-1-yl-carbonyl, 4-cyanothiazolidin-3-yl-carbonyl, 4-carboxythiazolidin-3-yl-carbonyl, 4-methoxycarbonylthiazolidin-3-yl-carbonyl, 4-ethoxy-carbonylthiazol idin-3-yl-carbonyl, 4-aminocarbonylthiazolidin-3-yl-carbonyl, piperidin-1-yl-carbonyl, morpholin-4-yl-carbonyl, piperazin-1-yl-carbonyl, 4-methyl-piperazin-1-yl-carbonyl or 4-ethyl-piperazin-1-yl-carbonyl group and Rg, which is separated by two carbon atoms from the nitrogen atom of the R8NRd group, denotes a hydroxy, methoxy or ethoxy group, a piperidin-1-yl or hexahydroazepin-1-yl group which is substituted in the 3 position or in the 4 position by an RQNRd group and may additionally be substituted by one or two C1.3-alkyl groups, wherein R. and Rd are as hereinbefore defined, a 3-amino-piperidin-1-yl group wherein the piperidin-1-yl moiety is additionally substituted by an aminocarbonyl, C1.2-alkyl-aminocarbonyl, di-(C1.2 al kyl)aminocarbonyl, pyrrolidin-1-yl-carbonyl, (2-cyano-pyrrolidin-1-yl-)carbonyl, thiazolidin-3-yi-carbonyl, (4-cyano-thiazolidin-3-yl)carbonyl, piperidin-l-ylcarbonyl or morpholin-4-ylcarbonyl group, a 3-amino-piperidin-1-yl group wherein the piperidin-1-yl moiety in the 4 position or in the 5 position is additionally substituted by a hydroxy or methoxy group, a 3-amino-piperidin-1-yl group wherein the methylene group in the 2 position or in the 6 position is replaced by a carbonyl group, a piperidin-1-yl or hexahydroazepin-1-yl- group substituted in the 3 position by an amino, C1-3-alkylamino or di-(C1.3-alkyl)-amino group, wherein in each case two hydrogen atoms at the carbon skeleton of the piperidin-1 -yl or hexahydroazepin-1-yl-group are replaced by a straight-chain alkylene bridge, this bridge containing 2 to 5 carbon atoms if the two hydrogen atoms are located on the same carbon atom, or to 4 carbon atoms if the hydrogen atoms are located on adjacent carbon atoms, or 1 to 4 carbon atoms, if the hydrogen atoms are located at carbon atoms separated by one atom, or 1 to 3 carbon atoms if the two hydrogen atoms are located at carbon atoms separated by two atoms, an azetidin-1-yl, pyrrolidin-1-yl, piperidin-1-yl or hexahydroazepin-1-yl group which is substituted by an amino-C1.3-alkyl, C1_3-alkylamino-C1.3-alkyl or a -(C1.3-alkyl)amino-C1.3-alkyl group, a piperazin-1-yl or [1,4]diazepan-1-yl group optionally substituted at the carbon skeleton by one or two C1_3-alkyl groups, a 3-imino-piperazin-1-yl, 3-imino-[1,4]diazepan-1-yl or 5-imino-[1,4]diazepan-1-yl group optionally substituted at the carbon skeleton by one or two C1.3-alkyl groups, a [1,4]diazepan-1-yl group optionally substituted by one or two C1.3-alkyl groups, which is substituted in the 6 position by an amino group, a C3_,-cycloalkyl group which is substituted by an amino, C1.3-alkylamino or di-(C1.3-alkyl)-amino group, a C3_7-cycloalkyl group which is substituted by an amino-C1.3-alkyl, C1.3-alkylamino-C1.3-alkyl or a di-(C1.3-alkyl)amino-Cl.3-alkyl group, a C3_7-cycloalkyl-C1.2-alkyl group wherein the cycloalkyl moiety is substituted by an amino, C1.3-alkylamino or di-(C,.3-alkyl)-amino group, a C3_,-cycloalkyl-C1_2-alkyl group wherein the cycloalkyl moiety is substituted by an amino-C1.3-alkyl, C1.3-alkylamino-C1_3-alkyl or a di-(C1.3-alkyl)amino-C1.3-alkyl group, a C3_,-cycloalkylamino group wherein the cycloalkyl moiety is substituted by an amino, C1.3-alkylamino or di-(C1.3-alkyl)-amino group, wherein the two nitrogen atoms on the cycloalkyl moiety are separated from one another by at least two carbon atoms, an N-(C3a-cycloalkyl)-N-(C1.3-alkyl)-amino group wherein the cycloalkyl moiety is substituted by an amino, C1.3-alkylamino or di-(C1.3-alkyl)-amino group, wherein the two nitrogen atoms on the cycloalkyl moiety are separated from one another by at least two carbon atoms, a C3.,-cycloalkylamino group wherein the cycloalkyl moiety is substituted by an amino-C1_3-alkyl, C1.3-alkylamino-C1.3-alkyl or a di-(C1.3-alkyl)amino-C1.3-alkyl group, an N-(C3.7-cycloalkyl)-N-(C,.3-alkyl)-amino group wherein the cycloalkyl moiety is substituted by an amino-C1.3-alkyl, C1.3-alkylamino-C1.3-alkyl or a di-(C,.3-alkyl)amino-C1.3-alkyl group, a C3_7-cycloalkyl-Cl.2-alkyl-amino group wherein the cycloalkyl moiety is substituted by an amino, C1.3-alkylamino or di-(C1.3-alkyl)-amino group, an N-(C3.7-cycloalkyl-Cl.2-alkyl)-N-(C,.2-alkyl)-amino group wherein the cycloalkyl moiety is substituted by an amino, C1.3-alkylamino or di-(C1.3-alkyl)-amino group, a C3.a-cycloalkyl-Cl.2-alkyl-amino group wherein the cycloalkyl moiety is substituted by an amino-C1.3-alkyl, C1.3-alkylamino-C1.3-alkyl or a di-(C1.3-alkyl)amino-C1.3-alkyl group, an N-(C3.7-cycloalkyl-Cl.2-alkyl)-N-(C,.2-alkyl)-amino group wherein the cycloalkyl moiety is substituted by an amino-C,.3-alkyl, C1.3-alkylamino-C,.3-alkyl or a di-(C1.3-alkyl)amino-C,.3-alkyl group, an amino group substituted by the groups R15 and R16 wherein R15 denotes a C1.6-alkyl group, a C3.6-cycloalkyl, C3.6-cycloalkyl-Cl.3-alkyl, aryl or aryl-C1.3-alkyl group and R16 denotes an R17-C2.3-alkyl group, wherein the C2.3-alkyl moiety is straight-chained and may be substituted by one to four C1.3-alkyl groups, which may be identical or different, or by an aminocarbonyl, C1.2-alkyl-aminocarbonyl, di-(C1.2-alkyl)aminocarbonyl, pyrrolidin-1-yl-carbonyl, (2-cyano-pyrrolidin-l -yl)carbonyl, thiazolidin-3-yl-carbonyl, (4-cyano-thiazolidin-3-yl)carbonyl, piperidin-1 -ylcarbonyl or morpholin-4-ylcarbonyl group and R17 denotes an amino, C1.3-alkylamino or di-(C1.3-alkyl)-amino group, wherein, if R3 denotes a methyl group, R" cannot represent a di-(C1.3-alkyl)-amino group, an amino group substituted by R20, wherein R20 denotes an azetidin-3-yl, azetidin-2-ylmethyl, azetidin-3-ylmethyl, pyrrolidin-3-yl, pyrrolidin-2-ylmethyl, pyrrolidin-3-ylmethyl, piperidin-3-yl, piperidin-4-yi, piperidin-2-ylmethyl, piperidin-3-ylmethyl or piperidin-4-ylmethyl group, while the groups mentioned for R20 may each be substituted by one or two C1.3-alkyl groups, an amino group substituted by the groups R15 and R20, wherein R15 and R20 are as hereinbefore defined, while the groups mentioned for R20 may each be substituted by one or two C1.3-alkyl groups, an R19-C3-4-alkyl group wherein the C3-4-alkyl moiety is straight-chained and may be substituted by the group R15 and may additionally be substituted by one or two C1.3-alkyl groups, wherein R15 is as hereinbefore defined and R19 denotes an amino, C1.3-alkylamino or di-(C1-3-alkyl)-amino group, a 3-amino-2-oxo-piperidin-5-yl or 3-amino-2-oxo-l-methyl-piperidin-5-yl group, a pyrrolidin-3-yl, piperidin-3-yl, piperidin-4-yl, hexahydroazepin-3-yl or hexahydroazepin-4-yl group which is substituted in the 1 position by an amino, C1.3-alkylamino or di-(C1.3-alkyl)amino group, or an azetidin-2-yl-C1.2-alkyl, azetidin-3-yl-C1.2-alkyl, pyrrolidin-2-yl-C1.2-alkyl, pyrrolidin-3-yl, pyrrolidin-3-yl-C1.2-alkyl, piperidin-2-yl-C1.2-alkyl, piperidin-3-yl, piperidin-3-yl-C1.2-alkyl, piperidin-4-yl or piperidin-4-yl-C1.2-alkyl group, wherein the abovementioned groups may each be substituted by one or two C1_3-alkyl groups, while by the aryl groups mentioned in the definition of the groups mentioned above are meant phenyl or naphthyl groups which may be mono- or disubstituted by Rh independently of one another, while the substituents may be identical or different and Rh denotes a fluorine, chlorine, bromine or iodine atom, a trifluoromethyl, cyano, nitro, amino, aminocarbonyl, aminosulphonyl, methylsulphonyl, acetylamino, methylsulphonylamino, C1.3-alkyl, cyclopropyl, ethenyl, ethynyl, hydroxy, C1.3-alkyloxy, difluoromethoxy or trifluoromethoxy group, by the heteroaryl groups mentioned in the definition of the groups mentioned above is meant a pyrrolyl, furanyl, thienyl, pyridyl, indolyl, benzofuranyl, benzothiophenyl, quinolinyl or isoquinolinyl group, or a pyrrolyl, furanyl, thienyl or pyridyl group wherein one or two methyne groups are replaced by nitrogen atoms, or an indolyl, benzofuranyl, benzothiophenyl, quinolinyl or isoquinolinyl group wherein one to three methyne groups are replaced by nitrogen atoms, or a 1,2-dihydro-2-oxo-pyridinyl, 1,4-dihydro-4-oxo-pyridinyl, 2,3-dihydro-3-oxo-pyridazinyl, 1,2,3,6-tetrahydro-3,6-dioxo-pyridazinyl, 1,2-dihydro-2-oxo-pyrimidinyl, 3,4-dihydro-4-oxo-pyrimidinyl, 1,2,3,4-tetrahydro-2,4-dioxo-pyrimidinyl, 1,2-dihydro-2-oxo-pyrazinyl, 1,2,3,4-tetrahydro-2,3-dioxo-pyrazinyl, 2,3-dihydro-2-oxo-indolyl, 2,3-di hydrobenzofuranyl, 2,3-dihydro-2-oxo-1 H-benzimidazolyl, 2,3-dihydro-2-oxo-benzoxazolyl, 1,2-dihydro-2-oxo-quinolinyl, 1,4-dihydro-4-oxo-quinolinyl, 1,2-dihydro-1-oxo-isoquinolinyl, 1,4-dihydro-4-oxo-cinnolinyl, 1,2-dihydro-2-oxo-quinazolinyl, 1,4-dihydro-4-oxo-quinazolinyl, 1,2,3,4-tetrahydro-2,4-dioxo-quinazolinyl, 1,2-dihydro-2-oxoquinoxalinyl, 1,2,3,4-tetrahydro-2,3-dioxo-quinoxalinyl, 1,2-dihydro-l -oxo-phthalazinyl, 1,2,3,4-tetrahydro-1,4-dioxo-phthalazinyl, chromanyl, cumarinyl, 2,3-dihydro-benzo[1,4]dioxinyl or 3,4-dihydro-3-oxo-2H-benzo[1,4]oxazinyl group, wherein the abovementioned heteroaryl groups may be substituted by R10 to R14, wherein R10 to R14 are as hereinbefore defined, while, unless otherwise stated, the abovementioned alkyl, alkenyl and alkynyl groups may be straight-chain or branched, as well as the derivatives which are N-oxidised or methylated or ethylated at the cyclic nitrogen atom in the 9 position of the xanthine skeleton, as well as the derivatives wherein the 2-oxo, the 6-oxo- or the 2-oxo- and the 6-oxo group of the xanthine skeleton are replaced by thioxo groups, with the proviso that the compounds wherein R1 denotes a hydrogen atom, a methyl, propyl, 2-hydroxypropyl, aminocarbonyl-methyl or benzyl group, R2 denotes a methyl group, R3 denotes a C,_8-alkyl group, a benzyl group optionally substituted by a fluorine, chlorine or bromine atom or by a methyl group, a 1-phenylethyl or 2-phenylethyl group, a 2-propen-1-yl, 2-buten-1 -yl, 3-chloro-2-buten-1 -yl or 2-methyl-2-propen-1 -yl group and R4 denotes a piperazin-1-yl group, are excluded, and with the proviso that the compounds wherein R1 denotes a hydrogen atom or a methyl group, R2 denotes a hydrogen atom or a methyl group, R3 denotes a methyl group and R4 denotes a 3-aminopropyl, 3-[di-(C1.3-alkyl)amino]-propyl, 1-phenyl-3-[di-(C1-3-alkyl)amino]-propyl, 1-phenyl-3-methyl-3-(dimethylamino)-propyl, 1-(4-chlorophenyl)-3-(dimethylami no)-propyl, 1-phenyl-2-methyl-3-(dimethylamino)-propyl, 1-(3-methoxyphenyl)-3-(dimethylamino)-propyl or a 4-aminobutyl group, are excluded, and with the proviso that the compound 1,3,7-trimethyl-8-(1-aminocyclohexyl)-xanthine is excluded, the tautomers, enantiomers, diastereomers, mixtures thereof and the salts thereof.
The carboxy groups mentioned in the definition of the abovementioned groups may be replaced by a group which can be converted into a carboxy group in vivo or by a group which is negatively charged under physiological conditions, and furthermore the amino and imino groups mentioned in the definition of the abovementioned groups may be substituted by a group which can be cleaved in vivo. Such groups are described for example in WO 98/46576 and by N.M. Nielsen et al. in International Journal of Pharmaceutics 39, 75-85 (1987).

By a group which can be converted in vivo into a carboxy group is meant, for example, a hydroxymethyl group, a carboxy group esterified with an alcohol wherein the alcohol moiety is preferably a C1.6-alkanol, a phenyl-C1_3-alkanol, a C3-9-cycloalkanol, while a C5.8-cycloalkanol may additionally be substituted by one or two C1.3-alkyl groups, a C5_8-cycloalkanol wherein a methylene group in the 3 or 4 .19-position is replaced by an oxygen atom or by an imino group optionally substituted by a C1.3-alkyl, phenyl-C1.3-alkyl, phenyl-C1.3-alkoxycarbonyl or C2.6-alkanoyl group and the cycloalkanol moiety may additionally be substituted. by one or two C1.3-alkyl groups, a C4.7-cycloalkenol, a C3.5-alkenol, a phenyl-C3.5-alkenol, a C3.5-alkynol or phenyl-C3.5-alkynol with the proviso that no bonds to the oxygen atom start from a carbon atom which carries a double or triple bond, a C3.8-cycloalkyl-C1.3-alkanol, a bicycloalkanol with a total of 8 to 10 carbon atoms which may additionally be substituted in the bicycloalkyl moiety by one or two C1.3-alkyl groups, a 1,3-dihydro-3-oxo-1-isobenzofuranol or an alcohol of formula Rp-CO-O-(RgCRr)-OH, wherein Rp denotes a C1.8-alkyl, C5.7-cycloalkyl, phenyl or phenyl-Cl.3-alkyl group, Rq denotes a hydrogen atom, a C1.3-alkyl, C5 rcycloalkyl or phenyl group and Rr denotes a hydrogen atom or a C1_3-alkyl group, by a group which is negatively charged under physiological conditions is meant, for "7 example, a tetrazol-5-yl, phenylcarbonylaminocarbonyl, trifluoromethylcarbonylaminocarbonyl, C1.6-alkylsulphonylamino, phenylsulphonylamino, bhnzylsulphonylamino, trifluoromethylsulphonylamino, C1.6-alkylsulphonylaminocarbonyl, phenylsulphonylaminocarbonyl, bhezylsulphonylaminocarbonyl or perfluoro-Cl.6-alkylsulphonylaminocarbonyl group and by a group which can be cleaved in vivo from an imino or amino group is meant, for example, a hydroxy group, an acyl group such as a phenylcarbonyl group optionally mono- or disubstituted by fluorine, chlorine, bromine or iodine atoms, by C1.3-alkyl or C1.3-alkoxy groups, while the substituents may be identical or different, a pyridinoyl group or a C1.16-alkanoyl group such as the formyl, acetyl, propionyl, butanoyl, pentanoyl or hexanoyl group, a 3,3,3-trichioropropionyl or allyloxycarbonyl group, a C,_16-alkoxycarbonyl or C1.16-alkylcarbonyloxy group, wherein hydrogen atoms may be wholly or partially replaced by fluorine or chlorine atoms such as the methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, tert.butoxycarbonyl, pentoxycarbonyl, hexoxycarbonyl, 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 group, a phenyl-Cl.6-alkoxycarbonyl group such as the benzyloxycarbonyl, phenylethoxycarbonyl or phenylpropoxycarbonyl group, a 3-amino-propionyl group wherein the amino group may be mono- or disubstituted by C1.6-alkyl or C3_7-cycloalkyl groups and the substituents may be identical or different, a C1.3-alkylsulphonyl-C2.4-alkoxycarbonyl, C1.3-alkoxy-C2.4-alkoxy-C2.4-alkoxycarbonyl, RP CO-O-(RgCRr)-O-CO, C1.6-alkyl-CO-NH-(RSCRt)-O-CO- or C1.6-alkyl-CO-O-(RCR1)-(R$CRt)-O-CO- group, wherein Rp to Rr are as hereinbefore defined, RS and Rt, which may be identical or different, denote hydrogen atoms or C1.3-alkyl groups.

Moreover, unless otherwise stated, the saturated alkyl and alkoxy moieties containing more than 2 carbon atoms mentioned in the definitions above also include the branched isomers thereof such as the isopropyl, tert.butyl, isobutyl group, etc.

R1 and R2 may denote, for example a hydrogen atom, a methyl, ethyl, propyl, 2-propyl, butyl, 2-butyl, 2-methylpropyl, 2-propen-1-yl, 2-propyn-1-yl, cyclopropylmethyl, benzyl, 2-phenylethyl, phenylcarbonylmethyl, 3-phenylpropyl, 2-hydroxyethyl, 2-methoxyethyl, 2-ethoxyethyl, 2-(dimethylamino)ethyl, 2-(di-ethylami no) ethyl, 2-(pyrrolidino)ethyl, 2-(piperidino)ethyl, 2-(morpholino)ethyl, 2-(piperazino)ethyl, 2-(4-methyl piperazino)ethyl, 3-hydroxypropyl, 3-methoxypropyl, 3-ethoxypropyl, 3-(dimethylamino)propyl, 3-(diethylamino)propyl, 3-(pyrrolidino)propyl, 3-(piperidino)propyl, 3-(morpholino)propyl, 3-(piperazino)-propyl, 3-(4-methylpiperazino)propyl, carboxymethyl, (methoxycarbonyl)methyl, (ethoxycarbonyl)methyl, 2-carboxyethyl, 2-(methoxycarbonyl)ethyl, 2-(ethoxy-carbonyl)ethyl, 3-carboxypropyl, 3-(methoxycarbonyl)propyl, 3-(ethoxycarbonyl)-propyl, (aminocarbonyl)methyl, (methylaminocarbonyl)methyl, (dimethylamino-carbonyl)methyl, (pyrrolidinocarbonyl)methyl, (piperidinocarbonyl)methyl, (morpholinocarbonyl)methyl, 2-(aminocarbonyl)ethyl, 2-(methylaminocarbonyl)ethyl, 2-(dimethylaminocarbonyl)ethyl, 2-(pyrrolidinocarbonyl)ethyl, 2-(piperidinocarbonyl)-ethyl, 2-(morpholinocarbonyl)ethyl, cyanomethyl or 2-cyanoethyl group.

R3 may denote, for example, a methyl, ethyl, propyl, 2-propyl, butyl, 2-butyl, methylpropyl, pentyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, cyclopropylmethyl, (1-methylcyclopropyl)methyl, (2-methylcyclopropyl)methyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, 2-(cyclopropyl)ethyl, 2-propen-1-yl, 2-methyl-2-propen-1-yl, 3-phenyl-2-propen-1-yl, 2-buten-1-yl, 4,4,4-trifluoro-2-buten-1-yl, 3-buten-1-yl, 2-chloro-2-buten-1-yl, 2-bromo-2-buten-1-yl, 3-chloro-2-buten-1-yl, 3-bromo-2-buten-1-yl, 2-methyl-2-buten-1-yl, 3-methyl-2-buten-1-yl, 2,3-dimethyl-2-buten-1-yl, 3-trifluoromethyl-2-buten-1-yl, 3-methyl-3-buten-l-yl,1-cyclopenten-1-ylmethyl, (2-methyl-l -cyclopenten-1-yl)methyl, 1 -cyclohexen-l -ylmethyl, 2-(1-cyclopenten-1-yl)ethyl, 2-propyn-1-yl, 2-butyn-1-yl, 3-butyn-1-yl, phenyl, methylphenyl, benzyl, a fluorobenzyl, chlorobenzyl, bromobenzyl, methylbenzyl, methoxybenzyl, 1-phenylethyl, 2-phenylethyl, 3-phenylpropyl, 2-furanylmethyl, 3-furanylmethyl, 2-thienylmethyl- or 3-thienylmethyl group.

R4 may denote, for example, a 3-aminopyrrolidin-1-yl, 3-aminopiperidin-1-yl, 3-(methylamino)-piperidin-1-yl, 3-(ethylamino)-piperidin-1-yl, 3-(dimethylamino)-piperidin-1-yl, 3-(diethylamino)-piperidin-1-yl, 3-[(2-hydroxyethyl)amino]-piperidin-l -yl, 3-[N-methyl-N-(2-hydroxyethyl)-amino]-piperidin-1-yl, 3-[(3-hydroxypropyl)amino]-piperidin-1-yl, 3-[N-methyl-N-(3-hydroxypropyl)-amino}-piperidin-1-yl, 3-[(carboxy-methyl)amino]-piperidin-1-yl, 3-[(methoxycarbonylmethyl)amino]-piperidin-1-yi, 3-[(ethoxycarbonylmethyl)amino]-piperidin-1-yl, 3-[N-methyl-N-(methoxycarbonyl-methyl)-amino]-piperidin-1-yl, 3-[N-methyl-N-(ethoxycarbonylmethyl)-amino]-piperidin-1-yl, 3-[(2-carboxyethyl)amino]-piperidin-1-yl, 3-{[2-(methoxycarbonyl)ethyl]amino}-piperidin-1-yl, 3-{[2-(ethoxycarbonyl)ethyl]amino}-piperidin-1-yl, 3-{N-methyl-N-[2-(methoxycarbonyl)ethyl]-amino}-piperidin-1-yl, 3-{N-methyl-N-[2-(ethoxycarbonyl)ethyl]-amino}-piperidin-1-yl, 3-[(aminocarbonylmethyl)-amino]-piperidin-1-yl, 3-[(methylaminocarbonylmethyl)amino]-piperidin-1-yl, 3-[(dimethylaminocarbonylmethyl)amino]-piperidin-1-yl, 3-[(ethylaminocarbonylmethyl)amino]-piperidin-1-yl, 3-[(diethyl aminocarbonylmethyl)amino]-piperidin-1-yl, 3-[(pyrrolidin-1-ylcarbonyl-methyl)amino]-piperidin-1-yl, 3-[(2-cyanopyrrolidin-1-ylcarbonylmethyl)amino]-piperidin-1-yl, 3-[(4-cyanothiazolidin-3-ylcarbonylmethyl)amino]-piperidin-1-yl, 3-[(2-aminocarbonylpyrrolidin-1-ylcarbonylmethyl)amino]-piperidin-1-yl, 3-[(2-carboxypyrrolidin-1-ylcarbonylmethyl)amino]-piperidin-1-yi, 3-[(2-methoxycarbonylpyrrolidin-1-ylcarbonylmethyl)amino]-piperidin-1-yl, 3-[(2-ethoxycarbonylpyrrolidin-1-ylcarbonylmethyl)amino]-piperidin-1-yl, 3-[(piperidin-1-ylcarbonylmethyl)amino]-piperidin-1-yl, 3-[(morpholin-4-ylcarbonylmethyl)amino]-pi-peridin-1-yl, 3-amino-2-methyl-piperidin-1 -yl, 3-amino-3-methyl-piperidin-1-yl, 3-amino-4-methyl-piperidin-1-yl, 3-amino-5-methyl-piperidin-1-yl, 3-amino-6-methyl-piperidin-1-yl, 2-amino-8-aza-bicyclo[3.2.1 ]oct-8-yl, 6-amino-2-aza-bicyclo[2.2.2]oct-2-yl, 4-aminopiperidin-1-yl, 3-amino-hexahydroazepin-1-yl, 4-amino-hexahydroazepin-1-yl, piperazin-1-yl, [1,4]diazepan-1-yl, 3-aminocyclopentyl, aminocyclohexyl, 3-(methylamino)-cyclohexyl, 3-(ethylamino)-cyclohexyl, 3-(dimethylami no)-cyclohexyl, 3-(diethylamino)-cyclohexyl, 4-aminocyclohexyl, (2-aminocyclopropyl)amino, (2-aminocyclobutyl)amino, (3-aminocyclobutyl)amino, (2-aminocyclopentyl)amino, (3-aminocyclopentyl)amino, (2-aminocyclohexyl)amino or (3-aminocyclohexyl)amino group.

A sub-group deserving special mention relates to those compounds of general formula I wherein R' to R4 are as hereinbefore defined, with the extra proviso that the compounds wherein R4 denotes an optionally substituted piperazin-1 -yl or [1,4]diazepan-1-yl group are excluded, the tautomers, enantiomers, diastereomers, mixtures thereof and the salts thereof.

- 22a-In an invention embodiment, there is particularly provided a compound of formula N
N C
/R4 (I), O N N
I

a tautomer, enantiomer, diastereomer, mixture thereof or a salt thereof, wherein R1 denotes a hydrogen atom, a C1_6-alkyl group, a C3_6-alkenyl group, a C3_4-alkenyl group which is substituted by a C1_2-alkyloxy-carbonyl group, a C3_6-alkynyl group, a C3_6-cycloalkyl-C1.3-alkyl group, a phenyl group which may be substituted by a fluorine, chlorine or bromine atom or by a methyl, trifluoromethyl, hydroxy or methoxy group, a phenyl-C1_4-alkyl group wherein the phenyl moiety is substituted by R10 to R12, wherein R10 denotes a hydrogen atom, a fluorine, chlorine or bromine atom, - 22b-a C1-4-alkyl, trifluoromethyl, hydroxymethyl, C3-6-cycloalkyl, ethynyl or phenyl group, a hydroxy, C1.4-alkyloxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, phenoxy, benzyloxy, 2-propen-1-yloxy, 2-propyn-1-yloxy, cyano-C1.2-alkyloxy, C1_2-alkylsulphonyloxy, phenylsulphonyloxy, carboxy-C1-3-alkyloxy, C1_3-alkyloxy-carbonyl-C1.3-alkyloxy, aminocarbonyl-C1-3-alkyloxy, C1-2-alkyl-aminocarbonyl-C1-3-alkyloxy, di-(C1-2-alkyl)aminocarbonyl-C1-3-alkyloxy, pyrrolidin-1-yl-carbonyl-C1-3-alkyloxy, piperidin-1-ylcarbonyl-C1-3-alkyloxy, morpholin-4-ylcarbonyl-C1-3-alkyloxy, methylsulphanylmethoxy, methylsulphinylmethoxy, methylsulphonylmethoxy, C3_6-cycloalkyloxy or C3-6-cycloalkyl-C1-2-alkyloxy group, a carboxy, C1-3-alkyloxycarbonyl, carboxy-C1.3-alkyl, C1-3-alkyloxy-carbonyl-C1_3-alkyl, aminocarbonyl, C1.2-alkylaminocarbonyl, di-(C1-2-alkyl)aminocarbonyl, morpholin-4-ylcarbonyl or cyano group, a nitro, amino, C1_2-alkylamino, di-(C1_2-alkylamino, cyano-C1-2-alkylamino, [N-(cyano-Cl-2-alkyl)-N-C1-2-alkyl-amino], C1-2-alkyloxy-carbonyl-C1-2-alkylamino, C1-2-alkyl-carbonylamino, C1-2-alkyloxy-carbonylamino, C1-3-alkylsulphonylamino, bis-(C1.2-alkylsulphonyl)-amino, aminosuiphonylamino, C1-2-alkylamino-sulphonylamino, di-(C1.2-alkyl)amino-sulphonylamino, morpholin-4-yl-sulphonylamino, (C1-2-alkylamino)thiocarbonylamino, (C1.2-alkyloxy-carbonylamino)carbonylamino, aminocarbonylamino, C1.2-alkylaminocarbonylamino, di-(C1-2-alkyl)aminocarbonylamino or morpholin-4-ylcarbonylamino group, a 2-oxo-imidazolidin-1-yl, 3-methyl-2-oxo-imidazolidin-1-yl, 2,4-dioxo-imidazolidin-1-yl, 3-methyl-2,4-dioxo-imidazolidin-1-yl, 2,5-dioxo-imidazolidin-1-yl, 3-methyl-2,5-dioxo-imidazolidin-1-yl, 2-oxo-hexahydropyrimidin-1-yl or 3-methyl-2-oxo-hexahydropyrimidin-1-yl group, - 22c-or a C1_2-alkylsulphanyl, C1_2-alkylsulphinyl, C1_2-alkylsulphonyl, aminosulphonyl, C1_2-alkylaminosulphonyl or di-(C1_2-alkyl)aminosulphonyl group, and R11 and R12, which may be identical or different, denote a hydrogen, fluorine, chlorine or bromine atom or a methyl, cyano, trifluoromethyl or methoxy group, or, R11 together with R12, if they are bound to adjacent carbon atoms, also denote a methylenedioxy, difluoromethylenedioxy, 1,3-propylene or 1,4-butylene group, a phenyl-C1.3-alkyl group wherein the alkyl moiety is substituted by a carboxy, C1.2-alkyloxy-carbonyl, aminocarbonyl, C1_2-alkylaminocarbonyl or di-(C1_2-alkyl)aminocarbonyl group, a phenyl-C2_3-alkenyl group, wherein the phenyl moiety may be substituted by a fluorine, chlorine or bromine atom or by a methyl, trifluoromethyl or methoxy group, a phenyl-(CH2)m-A-(CH2)ngroup wherein the phenyl moiety is substituted by R10 to R12, wherein R10 to R12 are as hereinbefore defined and A denotes a carbonyl, hydroxyiminomethylene or C1_2-alkyloxyiminomethylene group, m denotes the number 0 or 1 and n denotes the number 1 or 2, 25771-826(S) - 22d -a phenylcarbonylmethyl group wherein the phenyl moiety is substituted by R10 to R12, wherein R10 to R12 are as hereinbefore defined and the methyl moiety is substituted by a methyl or ethyl group, a phenylcarbonylmethyl group wherein two adjacent hydrogen atoms of the phenyl moiety are replaced by a -0-CO-NH, -NH-CO-NH, -N=CH-NH, -N=CH-O or -O-CH2-CO-NH- bridge, wherein the abovementioned bridges may be substituted by one or two methyl groups, a phenyl-(CH2)m-B-(CH2)n group wherein the phenyl moiety is substituted by R10 to R12, wherein R10 to R'2, m and n are as hereinbefore defined and B denotes a methylene group which is substituted by a hydroxy or C1_2-alkyloxy group and is optionally additionally substituted by a methyl group, a naphthylmethyl or naphthylethyl group, wherein the naphthyl moiety is substituted in each case by R10 to R12, wherein R'0 to R12 are as hereinbefore defined, a [1,4]naphthoquinon-2-yl, chromen-4-on-3-yl or 1-oxoindan-2-yl group, a heteroaryl-C1.3-alkyl group, wherein by the term heteroaryl is meant a pyrrolyl, furanyl, thienyl, pyridyl, indolyl, benzofuranyl, benzothiophenyl, quinolinyl or isoquinolinyl group, or a pyrrolyl, furanyl, thienyl or pyridyl group wherein one or two methyne groups are replaced by nitrogen atoms, or an indolyl, benzofuranyl, benzothiophenyl, quinolinyl or isoquinolinyl group wherein one to three methyne groups are replaced by nitrogen atoms, - 22e-or a 1,2-dihydro-2-oxo-pyridinyl, 1,4-dihydro-4-oxo-pyridinyl, 2,3-dihydro-3-oxo-pyridazinyl, 1,2,3,6-tetrahydro-3,6-dioxo-pyridazinyl, 1,2-dihydro-2-oxo-pyrimidinyl, 3,4-dihydro-4-oxo-pyrimidinyl, 1,2,3,4-tetrahydro-2,4-dioxo-pyrimidinyl, 1,2-dihydro-2-oxo-pyrazinyl, 1,2,3,4-tetrahydro-2,3-dioxo-pyrazinyl, 2,3-dihydro-2-oxo-indolyi, 2,3-dihydrobenzofuranyl, 2,3-dihydro-2-oxo-1 H-benzimidazolyl, 2,3-dihydro-2-oxo-benzoxazolyl, 1,2-dihydro-2-oxo-quinolinyl, 1,4-dihydro-4-oxo-quinolinyl, 1,2-dihydro-1-oxo-isoquinolinyl, 1,4-dihydro-4-oxo-cinnolinyl, 1,2-dihydro-2-oxo-quinazolinyl, 1,4-dihydro-4-oxo-quinazolinyl, 1,2,3,4-tetrahydro-2,4-dioxo-quinazolinyl, 1,2-dihydro-2-oxoquinoxalinyl, 1,2,3,4-tetrahydro-2,3-dioxo-quinoxalinyl, 1,2-dihydro-l-oxo-phthalazinyl, 1,2,3,4-tetrahydro-1,4-dioxo-phthalazinyl, chromanyl, cumarinyl, 2,3-dihydro-benzo[1,4]dioxinyl or 3,4-dihydro-3-oxo-2H-benzo[1,4]oxazinyl group, wherein the abovementioned heteroaryl groups may be substituted by R10 to R12, wherein R10 to R12 are as hereinbefore defined, a furanyl-A-CH2, thienyl-A-CH2, thiazolyl-A-CH2 or pyridyl-A-CH2 group, wherein A
is as hereinbefore defined, a furanyl-B-CH2, thienyl-B-CH2, thiazolyl-B-CH2 or pyridyl-B-CH2 group, wherein B
is as hereinbefore defined, a C1_4-alkyl-A-(CH2)n group, wherein A and n are as hereinbefore defined, a C3_6-cycloalkyl-(CH2)m-A-(CH2)n group, wherein A, m and n are as hereinbefore defined, a C3_6-cycloalkyl-(CH2)m-B-(CH2)n group, wherein B, m and n are as hereinbefore defined, a R21-A-(CH2)n group wherein R21 denotes a C1.2-alkyloxycarbonyl, aminocarbonyl, C1_2-alkylaminocarbonyl, di-(C1_2-alkyl)aminocarbonyl, pyrrolidin-1-- 22f-yl-carbonyl, piperidin-1-yl-carbonyl or morpholin-4-yl-carbonyl group and A
and n are as hereinbefore defined, a phenyl-D-C1.3-alkyl group wherein the phenyl moiety is optionally substituted by a fluorine, chlorine or bromine atom, a methyl, trifluoromethyl or methoxy group and D denotes an oxygen or sulphur atom, a sulphinyl or sulphonyl group, a C1.4-alkyl group substituted by a group Ra, wherein Ra denotes a cyano, carboxy, C1.3-alkyloxy-carbonyl, aminocarbonyl, C1.2-alkyl-aminocarbonyl, di-(C1_2-alkyl)aminocarbonyl, pyrrolidin-1-yl-carbonyl, piperidin-1-ylcarbonyl or morpholin-4-ylcarbonyl group, a C2_4-alkyl group substituted by a group Rb, wherein Rb denotes a hydroxy, C1.3-alkyloxy, amino, C1.3-alkylamino, di-(C1_3-alkyl)-amino, pyrrolidin-1-yl, piperidin-1-yl, morpholin-4-yl, piperazin-1-yl, 4-methyl-piperazin-1-yl or 4-ethyl-piperazin-1-yl group and is isolated from the cyclic nitrogen atom in the 1 position of the xanthine skeleton by at least two carbon atoms, or an amino or benzoylamino group, R2 denotes a hydrogen atom, a C1_6-alkyl group, a C2_4-alkenyl group, a C3_4-alkynyl group, a C3_6-cycloalkyl group, - 22g-a C3_6-cycloalkyl-C1_3-alkyl group, a tetra hyd rofu ran -3-yl, tetra hydropyran-3-yl, tetra hydropyran-4-yl, tetrahydrofuranylmethyl or tetrahydropyranylmethyl group, a phenyl group which is optionally substituted by a fluorine, chlorine or bromine atom or by a methyl, trifluoromethyl, hydroxy, methoxy, difluoromethoxy or trifluoromethoxy group, a phenyl-C1.4-alkyl group wherein the phenyl moiety is optionally substituted by a fluorine, chlorine or bromine atom, a methyl, trifluoromethyl, dimethylamino, hydroxy, methoxy, difluoromethoxy or trifluoromethoxy group, a phenyl-C2_3-alkenyl group, wherein the phenyl moiety may be substituted by a fluorine, chlorine or bromine atom or by a methyl, trifluoromethyl or methoxy group, a phenylcarbonyl-C1.2-alkyl group wherein the phenyl moiety is optionally substituted by a fluorine, chlorine or bromine atom, a methyl, trifluoromethyl, hydroxy, methoxy, difluoromethoxy or trifluoromethoxy group, a heteroaryl-C1_3-alkyl group, wherein the term heteroaryl is as hereinbefore defined, a furanylcarbonylmethyl, thienylcarbonylmethyl, thiazolylcarbonylmethyl or pyridylcarbonylmethyl group, a C1_4-alkyl-carbonyl-C1_2-alkyl group, a C3_6-cycloalkyl-carbonyl-C1_2-alkyl group, - 22h-a phenyl-D-C1_3-alkyl group wherein the phenyl moiety is optionally substituted by a fluorine, chlorine or bromine atom, a methyl, trifluoromethyl, hydroxy, methoxy, difluoromethoxy or trifluoromethoxy group, and D is as hereinbefore defined, or a C1_4-alkyl group substituted by a group Ra, wherein Ra is as hereinbefore defined, or a C2_4-alkyl group substituted by a group Rb, wherein Rb is as hereinbefore defined and is isolated from the cyclic nitrogen atom in the 3 position of the xanthine skeleton by at least two carbon atoms, R3 denotes a C1.3-alkyl group substituted by the group Rc, wherein R, denotes a C3_7-cycloalkyl group optionally substituted by one or two C1_3-alkyl groups, a C5_7-cycloalkenyl group optionally substituted by one or two C1_3-alkyl groups or an aryl group or a furanyl, thienyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyridyl, pyridazinyl, pyrimidyl or pyrazinyl group, wherein the abovementioned heterocyclic groups may each be substituted by one or two C1_3-alkyl groups or by a fluorine, chlorine, bromine or iodine atom or by a trifluoromethyl, cyano or C1_3-alkyloxy group, a C3_8-alkenyl group, a C3_6-alkenyl group substituted by a fluorine, chlorine or bromine atom, or a trifluoromethyl group, a C3_8-alkynyl group, - 22i-an aryl group or an aryl-C2_4-alkenyl group, and R4 denotes an azetidin-1-yl or pyrrolidin-1-yl group which is substituted in the 3 position by an ReNRd group and may additionally be substituted by one or two C1_3-alkyl groups, wherein Re denotes a hydrogen atom or a C1.3-alkyl group and Rd denotes a hydrogen atom or a C1.3-alkyl group, a piperidin-1-yl or hexahydroazepin-1-yl group which is substituted in the 3 position or in the 4 position by an ReNRd group and may additionally be substituted by one or two C1_3-alkyl groups, wherein Re and Rd are as hereinbefore defined, a 3-amino-piperidin-1-yl group wherein the piperidin-1-yl moiety is additionally substituted by an aminocarbonyl, C1.2-alkyl-aminocarbonyl, di-(C1_2-alkyl)aminocarbonyl, pyrrolidin-1-yl-carbonyl, (2-cyano-pyrrolidin-1-yl-)carbonyl, thiazolidin-3-yl-carbonyl, (4-cyano-thiazolidin-3-yl)carbonyl, piperidin-1-ylcarbonyl or morpholin-4-ylcarbonyl group, a 3-amino-piperidin-1-yl group wherein the piperidin-1-yl moiety is additionally substituted in the 4 position or in the 5 position by a hydroxy or methoxy group, a 3-amino-piperidin-1-yI group wherein the methylene group is replaced in the position or in the 6 position by a carbonyl group, - 22j-a piperidin-1-yl or hexahydroazepin-1-yl group substituted in the 3 position by an amino, C1_3-alkylamino or di-(C1-3-alkyl)-amino group, wherein in each case two hydrogen atoms on the carbon skeleton of the piperidin-1-yl or hexahydroazepin-1-yl group are replaced by a straight-chain alkylene bridge, this bridge containing 2 to 5 carbon atoms if the two hydrogen atoms are located on the same carbon atom, or 1 to 4 carbon atoms if the hydrogen atoms are located on adjacent carbon atoms, or 1 to 4 carbon atoms if the hydrogen atoms are located on carbon atoms which are separated by one atom, or 1 to 3 carbon atoms if the two hydrogen atoms are located on carbon atoms separated by two atoms, an azetidin-1-yl, pyrrolidin-1-yl, piperidin-1-yl or hexahydroazepin-1-yl group which is substituted by an amino-C1-3-alkyl, C1-3-alkylamino-C1-3-alkyl or a di-(C1_3-alkyl)amino-Cl-3-alkyl group, a 3-imino-piperazin-1-yl, 3-imino-[1,4]diazepan-1-yl or 5-imino-[1,4]diazepan-1-yl group optionally substituted by one or two C1_3-alkyl groups on the carbon skeleton, a [1,4]diazepan-1-yl group optionally substituted by one or two C1-3-alkyl groups, which is substituted in the 6 position by an amino group, a C3-7-cycloalkyl group which is substituted by an amino, C1-3-alkylamino or di-(C1-3-alkyl)-amino group, a C3-7-cycloalkyl group which is substituted by an amino-C1-3-alkyl, C1-3-alkylamino-C1-3-alkyl or a di-(C1_3-alkylamino-C1-3-alkyl group, a C3_7-cycloalkyl-C1.2-alkyl group wherein the cycloalkyl moiety is substituted by an amino, C1-3-alkylamino or di-(C1_3-alkyl)-amino group, a C3_7-cycloalkyl-C1-2-alkyl group wherein the cycloalkyl moiety is substituted by an amino-C1-3-alkyl, C1_3-alkylamino-C1_3-alkyl or a di-(C1_3-alkyl)amino-C1.3-alkyl group, - 22k-a C3_7-cycloalkylamino group wherein the cycloalkyl moiety is substituted by an amino, C1.3-alkylamino or di-(C1.3-alkyl)-amino group, wherein the two nitrogen atoms are separated from one another at the cycloalkyl moiety by at least two carbon atoms, a N-(C3.7-cycloalkyl)-N-(C1_3-alkyl)-amino group wherein the cycloalkyl moiety is substituted by an amino, C1_3-alkylamino or di-(C1_3-alkyl)-amino group, wherein the two nitrogen atoms are separated from one another at the cycloalkyl moiety by at least two carbon atoms, a C3_7-cycloalkylamino group wherein the cycloalkyl moiety is substituted by an amino-C1.3-alkyl, C1_3-alkylamino-C1_3-alkyl or a di-(C1_3-alkyl)amino-C1_3-alkyl group, a N-(C3_7-cycloalkyl)-N-(C1_3-alkyl)-amino group wherein the cycloalkyl moiety is substituted by an amino-C1_3-alkyl, C1_3-alkylamino-C1.3-alkyl or a di-(C1_3-alkyl)amino-C1_3-alkyl group, a C3_7-cycloalkyl-C1.2-alkyl-amino group wherein the cycloalkyl moiety is substituted by an amino, C1.3-alkylamino or di-(C1_3-alkyl)-amino group, a N-(C3_7-cycloalkyl-C1_2-alkyl)-N-(C1_2-alkyl)-amino group wherein the cycloalkyl moiety is substituted by an amino, C1_3-alkylamino or di-(C1_3-alkyl)-amino group, a C3_7-cycloalkyl-C1_2-alkyl-amino group wherein the cycloalkyl moiety is substituted by an amino-C1.3-alkyl, C1_3-alkylamino-C1_3-alkyl or a di-(C1_3-alkyl)amino-C1.3-alkyl group, an N-(C3_7-cycloalkyl-C1_2-alkyl)-N-(C1_2-alkyl)-amino group wherein the cycloalkyl moiety is substituted by an amino-C1_3-alkyl, C1_3-alkylamino-C1_3-alkyl or a di-(C1.3-alkyl)amino-C1_3-alkyl group, an amino group substituted by the groups R15 and R16 wherein R15 denotes a C1_3-alkyl group and R16 denotes a R17-C2_3-alkyl group, wherein the C2.3-alkyl moiety is straight-chained and may be substituted by one to four C1_3-alkyl groups, which may be identical or different, or by an aminocarbonyl, C1.2-alkyl-aminocarbonyl, di-(C1_2-alkyl)aminocarbonyl, pyrrolidin-1-yl-carbonyl, (2-cyano-pyrrolidin-1-yl)carbonyl, thiazolidin-3-yl-carbonyl, (4-cyano-thiazolidin-3-yl)carbonyl, piperidin-1-ylcarbonyl or morpholin-4-ylcarbonyl group and R17 denotes an amino, C1_3-alkylamino or di-(C1_3-alkyl)-amino group, an amino group substituted by the group R20, wherein R20 denotes an azetidin-3-yl, azetidin-2-ylmethyl, azetidin-3-ylmethyl, pyrrolidin-3-yl, pyrrolidin-2-ylmethyl, pyrrolidin-3-ylmethyl, piperidin-3-yl, piperidin-4-yl, piperidin-2-ylmethyl, piperidin-3-ylmethyl or piperidin-4-ylmethyl group, wherein the groups mentioned for R20 may each be substituted by one or two C1_3-alkyl groups, an amino group substituted by the groups R15 and R20, wherein R15 and R20 are as hereinbefore defined, wherein the groups mentioned for R20 may each be substituted by one or two C1_3-alkyl groups, a R19-C3.4-alkyl group wherein the C34-alkyl moiety is straight-chained and may be substituted by the group R15 and may additionally be substituted by one or two C1.3-alkyl groups, wherein R15 is as hereinbefore defined and R19 denotes an amino, C1_3-alkylamino or di-(C1.3-alkyl)-amino group, a 3-amino-2-oxo-piperidin-5-yl or 3-amino-2-oxo-1-methyl-piperidin-5-yI group, - 22m-a pyrrolidin-3-yl, piperidin-3-yl, piperidin-4-yl, hexahydroazepin-3-yl or hexahydroazepin-4-yl group, which is substituted in the 1 position by an amino, C1_3-alkylamino or di-(C1_3-alkyl)amino group, or an azetidin-2-yl-C1_2-alkyl, azetidin-3-yI-C1_2-alkyl, pyrrolidin-2-yl-C1_2-alkyl, pyrrolidin-3-yl, pyrrolidin-3-yl-C1.2-alkyl, piperidin-2-yl-C1_2-alkyl, piperidin-3-yl, piperidin-3-yl-C1_2-alkyl, piperidin-4-yl or piperidin-4-yl-C1.2-alkyl group, wherein the abovementioned groups may each be substituted by one or two C1_3-alkyl groups, while by the aryl groups mentioned in the definition of the groups mentioned above are meant phenyl or naphthyl groups which may be mono- or disubstituted independently of one another by Rh, while the substituents may be identical or different and Rh denotes a fluorine, chlorine, bromine or iodine atom, a trifluoromethyl, cyano, nitro, amino, C1.3-alkyl, cyclopropyl, ethenyl, ethynyl, hydroxy, C1_3-alkyloxy, difluoromethoxy or trifluoromethoxy group and unless otherwise stated, the abovementioned alkyl and alkenyl groups may be straight-chained or branched, with the proviso that the compounds 1,3-diethyl-7-(4-methoxybenzyl)-8-[(piperidin-4-yl)amino]-xanthine, and 1,3-diethyl-7-(4-hydroxybenzyl)-8-[(piperidin-4-yl)amino]-xanthine are excluded.

In a further embodiment, R4 is an azetidin-1-yl or pyrrolidin-1-yl group which is substituted in the 3 position by an ReNRd group and may additionally be substituted by one or two C1_3-alkyl groups, wherein Re denotes a hydrogen atom or a C1_3-alkyl group and - 22n-Rd denotes a hydrogen atom or a C1.3-alkyl group, a piperidin-1-yl or hexahydroazepin-1-yl group which is substituted in the 3 position or in the 4 position by an ReNRd group and may additionally be substituted by one or two C1_3-alkyl groups, wherein Re and Rd are as hereinbefore defined.

In another embodiment, R2 is C1.6 alkyl.

A second sub-group deserving special mention relates to those compounds of general formula I wherein R1 denotes a hydrogen atom, a C,.6-alkyl group, a C3.6-alkenyl group, r a C3.4-alkenyl group which is substituted by a C1.2-alkyloxy-carbonyl group, a C3.6-alkynyl group, a C3.6-cycloalkyl-C,.3-alkyl group, a phenyl group which may be substituted by a fluorine, chlorine or bromine atom or by a methyl, trifluoromethyl, hydroxy or methoxy group, a phenyl-C1.4-alkyl group wherein the phenyl moiety is substituted by R10 to R12, wherein R10 denotes a hydrogen atom, a fluorine, chlorine or bromine atom, a C1.4-alkyl, trifluoromethyl, hydroxymethyl, C3.6-cycloalkyl, ethynyl or phenyl group, a hydroxy, C1.4-alkyloxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, phenoxy, benzyloxy, 2-propen-1-yloxy, 2-propyn-1-yloxy, cyano-Cl.2-alkyloxy, C1.2-alkylsulphonyloxy, phenylsulphonyloxy, carboxy-C,.3-alkyloxy, C,_3-alkyloxy-carbonyl-C1.3-alkyloxy, aminocarbonyl-C,.3-alkyloxy, C1.2-alkyl-aminocarbonyl-C1.3-alkyloxy, di-(C1.2-alkyl)aminocarbonyl-C1.3-alkyloxy, pyrrolidin-1-yl-carbonyl-C,.3-alkyloxy, pipe ridin-1-ylcarbonyl-C,_3-alkyloxy, morpholin-4-ylcarbonyl-C,_3-alkyloxy, methylsuiphanylmethoxy, methylsulphinylmethoxy, methylsulphonylmethoxy, C3_6-cycloalkyloxy or C3_6-cycloalkyl-C,_2-alkyloxy group, a carboxy, C1_3-alkyloxycarbonyl, carboxy-C,.3-alkyl, C1_3-alkyloxy-carbonyl-C1_3-alkyl, aminocarbonyl, C1_2-al kylaminocarbonyl, di-(C1.2-alkyl)aminocarbonyl, morpholin-4-ylcarbonyl or cyano group, a nitro, amino, C,_2-alkylamino, di-(C1.2-alkyl)amino, cyano-C1.2-alkylamino, [N-(cyano-C,_2-alkyl)-N-C,_2-alkyl-amino], C,.2-alkyloxy-carbonyl-C1.2-alkylamino, C,_2-alkyl-carbonylamino, C1_2-alkyloxy-carbonylamino, C,_3-al kylsulphonylamino, bis-(C1_2-alkylsulphonyl)-amino, aminosulphonylamino, C1.2-alkylamino-sulphonylamino, di-(C1.2-alkyl)amino-sulphonylamino, morpholin-4-yl-sulphonylamino, (C1.2-alkylamino)thiocarbonylamino, (C1.2-alkyloxy-carbonylamino)carbonylamino, aminocarbonylamino, C,.2-alkyl-aminocarbonylamino, di-(C,.2-alkyl)aminocarbonylamino or morpholin-4-ylcarbonylamino group, a 2-oxo-imidazolidin-1-yl, 3-methyl-2-oxo-imidazolidin-1-yl, 2,4-dioxo-imidazolidin-1-yl, 3-methyl-2,4-dioxo-imidazolidin-1-yl, 2,5-dioxo-imidazolidin-1 -yl, 3-methyl-2,5-dioxo-imidazolidin- 1 -yl, 2-oxo-hexahydropyrimidin-1 -yl or 3-methyl-2-oxo-hexahydropyrimidin-1-yl group, or a C1.2-alkylsulphanyl, C,_2-alkylsulphinyl, C,_2-alkylsulphonyl, aminosulphonyl, C1_2-alkylaminosulphonyl or di-(C,.2-alkyl)aminosulphonyl group, and R" and R12, which may be identical or different, denote a hydrogen, fluorine, chlorine or bromine atom or a methyl, cyano, trifluoromethyl or methoxy group, or, R" together with R12, if they are bound to adjacent carbon atoms, also denote a methylenedioxy, difluoromethylenedioxy, 1,3-propylene or 1,4-butylene group, a phenyl-C1.3-alkyl group wherein the alkyl moiety is substituted by a carboxy, C1.2-alkyloxy-carbonyl, aminocarbonyl, C1_2-alkylaminocarbonyl or di-(C1_2-alkyl)amino-carbonyl group, a PhenYl-C2.3-alkenYI group, wherein the phenyl moiety may be substituted by a fluorine, chlorine or bromine atom or by a methyl, trifluoromethyl or methoxy group, a phenyl-(CH2)m-A-(CH2)n group wherein the phenyl moiety is substituted by R10 to R12, wherein R10 to A12 are as hereinbefore defined and A denotes a carbonyl, hydroxyiminomethylene or C1.2-al kyloxyiminomethylene group, m denotes the number 0 or 1 and n denotes the number 1 or 2, a phenylcarbonylmethyl group wherein the phenyl moiety is substituted by R10 to R12, wherein R10 to R12 are as hereinbefore defined and the methyl moiety is substituted by a methyl or ethyl group, a phenylcarbonylmethyl group wherein two adjacent hydrogen atoms of the phenyl moiety are replaced by a -0-CO-NH, -NH-CO-NH, -N=CH-NH, -N=CH-O or O-CH2-CO-NH- bridge, wherein the abovementioned bridges may be substituted by one or two methyl groups, a phenyl-(CH2)m-B-(CH2)n group wherein the phenyl moiety is substituted by R10 to R12, wherein R10 to R12, m and n are as hereinbefore defined and B denotes a methylene group which is substituted by a hydroxy or C1.2-alkyloxy group and is optionally additionally substituted by a methyl group, a naphthylmethyl or naphthylethyl group, wherein the naphthyl moiety is substituted in each case by R10 to R12, wherein R10 to 812 are as hereinbefore defined, a [1,4]naphthoquinon-2-yl, chromen-4-on-3-yl or 1-oxoindan-2-yl group, a heteroaryl-C1.3-alkyl group, wherein the term heteroaryl denotes a pyrrolyl, imidazolyl, triazolyl, furanyl, thienyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, benzimidazolyl, 2,3-dihydro-2-oxo-1 H-benzimidazolyl, indazolyl, benzofuranyl, 2,3-dihydrobenzofuranyl, benzoxazolyl, dihydro-2-oxo-benzoxazolyl, benzoisoxazolyl, benzothiophenyl, benzothiazolyl, benzoisothiazolyl, quinolinyl, 1,2-dihydro-2-oxo-quinolinyl, isoquinolinyl, 1,2-dihydro-1-oxo-isoquinolinyl, cinnolinyl, quinazolinyl, 1,2-dihydro-2-oxo-quinazolinyl, 1,2-dihydro-1-oxo-phthalazin-4-yl, cumarinyl or 3,4-dihydro-3-oxo-2H-benzo[1,4]oxazinyl group, wherein the abovementioned heteroaryl groups may be substituted at carbon atoms by a fluorine, chlorine or bromine atom, by a methyl, trifluoromethyl, cyano, aminocarbonyl, aminosuiphonyl, methylsuiphonyl, nitro, amino, acetylamino, methylsulphonylamino, methoxy, difluoromethoxy or trifluoromethoxy group and the imino groups of the abovementioned heteroaryl groups may be substituted by methyl or ethyl groups, a furanyl-A-CH2, thienyl-A-CH2, thiazolyl-A-CH2 or pyridyl-A-CH2 group, wherein A is as hereinbefore defined, a furanyl-B-CH2, thienyl-B-CH2, thiazolyl-B-CH2 or pyridyl-B-CH2 group, wherein B is as hereinbefore defined, a C1_4-alkyl-A-(CH2)n group, wherein A and n are as hereinbefore defined, a C3.6-cycloalkyl-(CH2),,,-A-(CH2)n group, wherein A, m and n are as hereinbefore defined, a C3.6-cycloalkyl-(CH2)m-B-(CH2)õ group, wherein B, m and n are as hereinbefore defined, a R21-A-(CH2)õ group wherein R21 denotes a C1.2-alkyloxycarbonyl, aminocarbonyl, C1.2-alkylaminocarbonyl, di-(C1.2-alkyl)aminocarbonyl, pyrrolidin-1-yl-carbonyl, piperidin-1-yl-carbonyl or morpholin-4-yl-carbonyl group and A and n are as hereinbefore defined, a phenyl-D-C1.3-alkyl group wherein the phenyl moiety is optionally substituted by a fluorine, chlorine or bromine atom, a methyl, trifluoromethyl or methoxy group and D
denotes an oxygen or sulphur atom, a sulphinyl or sulphonyl group, a C1.4-alkyl group substituted by a group Ra, wherein R. denotes a cyano, carboxy, C1.3-alkyloxy-carbonyl, aminocarbonyl, C1.2-alkyl-aminocarbonyl, di-(C1.2-alkyl)aminocarbonyl, pyrrolidin-1-yl-carbonyl, piperidin-1-ylcarbonyl or morpholin-4-ylcarbonyl group, a C2.4-alkyl group substituted by a group Rb, wherein Rb denotes a hydroxy, C1.3-alkyloxy, amino, C1.3-alkylamino, di-(C1.3-alkyl)-amino, pyrrolidin-1-yl, piperidin-1-yl, morpholin-4-yl, piperazin-1-yl, 4-methyl-piperazin-1 -yl or 4-ethyl-piperazin-1 -yl group and is isolated from the cyclic nitrogen atom in the 1 position of the xanthine skeleton by at least two carbon atoms, or an amino or benzoylamino group, R 2 denotes a hydrogen atom, a C1.6-alkyl group, a C2F4-alkenyl group, a C3.4-alkynyl group, a C3_6-cycloalkyl group, a Ca.6-cycloalkyl-C1.3-alkyl group, a tetrahydrofuran-3-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, tetrahydrofuranylmethyl or tetrahydropyranylmethyl group, a phenyl group which is optionally substituted by a fluorine, chlorine or bromine atom or by a methyl, trifluoromethyl, hydroxy, methoxy, difluoromethoxy or trifluoromethoxy group, a phenyl-C1.4-alkyl group wherein the phenyl moiety is optionally substituted by a fluorine, chlorine or bromine atom, a methyl, trifluoromethyl, dimethylamino, hydroxy, methoxy, difluoromethoxy or trifluoromethoxy group, a phenyl-C2-ralkenyl group, wherein the phenyl moiety may be substituted by a fluorine, chlorine or bromine atom or by a methyl, trifluoromethyl or methoxy group, a phenylcarbonyl-C1.2-alkyl group wherein the phenyl moiety is optionally substituted by a fluorine, chlorine or bromine atom, a methyl, trifluoromethyl, hydroxy, methoxy, difluoromethoxy or trifluoromethoxy group, a heteroaryi-Cl.3-alkyl group, wherein the term heteroaryl is as hereinbefore defined, a fu ranylcarbonylmethyl, thienylcarbonylmethyl, thiazolylcarbonylmethyl or pyridylcarbonylmethyl group, a C1.4-alkyl-carbonyl-Cl.2-alkyl group, a C3_6-cycloalkyl-carbonyl-Cl.2-alkyl group, a phenyl-D-C1.3-alkyl group wherein the phenyl moiety is optionally substituted by a fluorine, chlorine or bromine atom, a methyl, trifluoromethyl, hydroxy, methoxy, difluoromethoxy or trifluoromethoxy group, and D is as hereinbefore defined, or a C1.4-alkyl group substituted by a group Ra, wherein R. is as hereinbefore defined, or a C2_4-alkyl group substituted by a group Rb, wherein Rb is as hereinbefore defined and is isolated from the cyclic nitrogen atom in the 3 position of the xanthine skeleton by at least two carbon atoms, R3 denotes a C1_3-alkyl group substituted by the group Rc, wherein Rc denotes a C3.7-cycloalkyl group optionally substituted by one or two C1.3-alkyl groups, a C&7-cycloalkenyl group optionally substituted by one or two C1.3-alkyl groups or an aryl group or a furanyl, thienyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyridyl, pyridazinyl, pyrimidyl or pyrazinyl group, wherein the abovementioned heterocyclic groups may each be substituted by one or two C1.3-alkyl groups or by a fluorine, chlorine, bromine or iodine atom or by a trifluoromethyl, cyano or C1.3-alkyloxy group, a C3.8-alkenyl group, a C3.6-alkenyl group substituted by a fluorine, chlorine or bromine atom, or a trifluoromethyl group, a C3_8-alkynyl group, I
an aryl group or an aryl-C2.4-alkenyl group, and R4 denotes an azetidin-1-yl or pyrrolidin-1-yl group which is substituted in the 3 position by an ReNRd group and may additionally be substituted by one or two C1.3-alkyl groups, wherein R. denotes a hydrogen atom or a C1.3-alkyl group and Rd denotes a hydrogen atom or a C1_3-alkyl group, a piperidin-1 -yl or hexahydroazepin-1 -yl group which is substituted in the 3 position or in the 4 position by an ReNRd group and may additionally be substituted by one or two C1.3-alkyl groups, wherein Re and Rd are as hereinbefore defined, a 3-amino-piperidin-1 -yl group wherein the piperidin-1 -yl moiety is additionally substituted by an aminocarbonyl, C1_2-alkyl-aminocarbonyl, di-(C1.2-alkyl)aminocarbonyl, pyrrolidin-1-yl-carbonyl, (2-cyano-pyrrolidin-1-yl-)carbonyl, thiazolidin-3-yl-carbonyl, (4-cyano-thiazolidin-3-yl)carbonyl, piperidin-1-ylcarbonyl or morpholin-4-ylcarbonyl group, a 3-amino-piperidin-1 -yl group wherein the piperidin-1 -yl moiety is additionally substituted in the 4 position or in the 5 position by a hydroxy or methoxy group, a 3-amino-piperidin-1-yl group wherein the methylene group is replaced in the position or in the 6 position by a carbonyl group, a piperidin-1 -yl or hexahydroazepin-1 -yl group substituted in the 3 position by an amino, C1.3-alkylamino or di-(C1.3-alkyl)-amino group, wherein in each case two hydrogen atoms on the carbon skeleton of the piperidin-1-yl or hexahydroazepin-1-yl group are replaced by a straight-chain alkylene bridge, this bridge containing 2 to 5 carbon atoms if the two hydrogen atoms are located on the same carbon atom, or to 4 carbon atoms if the hydrogen atoms are located on adjacent carbon atoms, or 1 to 4 carbon atoms if the hydrogen atoms are located on carbon atoms which are separated by one atom, or 1 to 3 carbon atoms if the two hydrogen atoms are located on carbon atoms separated by two atoms, an azetidin-1-yl, pyrrolidin-1-yl, piperidin-1-yl or hexahydroazepin-1-yl group which is substituted by an amino-C1.3-alkyl, C1.3-alkylamino-C1.3-alkyl or a di-(C1.3-alkyl)amino-C1.3-alkyl group, a 3-imino-piperazin-1-yl, 3-imino-[1,4]diazepan-1-yl or 5-imino-[1,4]diazepan-1-yl group optionally substituted by one or two C1.3-alkyl groups on the carbon skeleton, a [1,4]diazepan-1-yl group optionally substituted by one or two C1.3-alkyl groups, which is substituted in the 6 position by an amino group, a C3.,-cycloalkyl group which is substituted by an amino, C1.3-alkylamino or di-(C1.3-alkyl)-amino group, = -32-a C3a-cycloalkyl group which is substituted by an amino-C1.3-alkyl, C1.3-alkylamino-C1-3-alkyl or a di-(C1.3-alkyl)amino-Cl-3-alkyl group, a C3.7-cycloalkyl-Cl.2-alkyl group wherein the cycloalkyl moiety is substituted by an amino, C1.3-alkylamino or di-(Ct.3-alkyl)-amino group, a C3.7-cycloalkyl-C1_2-alkyl group wherein the cycloalkyl moiety is substituted by an amino-Cl.3-alkyl, C1-3-alkylamino-C13-alkyl or a di-(C1.3-alkyl)amino-Cl.3-alkyl group, a C3.7-cycloalkylamino group wherein the cycloalkyl moiety is substituted by an amino, C1.3-alkylamino or di-(C1.3-alkyl)-amino group, wherein the two nitrogen atoms are separated from one another at the cycloalkyl moiety by at least two carbon atoms, a N-(C3.7-cycloalkyl)-N-(C1.3-alkyl)-amino group wherein the cycloalkyl moiety is substituted by an amino, C1.3-alkylamino or di-(C1.3-alkyl)-amino group, wherein the two nitrogen atoms are separated from one another at the cycloalkyl moiety by at least two carbon atoms, a C3.7-cycloalkylamino group wherein the cycloalkyl moiety is substituted by an amino-Cl.3-alkyl, C1.3-alkylamino-Cl.3-alkyl or a di-(C1.3-alkyl)amino-Cl.3-alkyl group, a N-(C3.7-cycloalkyl)-N-(C1.3-alkyl)-amino group wherein the cycloalkyl moiety is substituted by an amino-C1.3-alkyl, C1.3-alkylamino-Cl.3-alkyl or a di-(C1.3-alkyl)amino-C1.3-alkyl group, a C3_,-cycloalkyl-Cl.2-alkyl-amino group wherein the cycloalkyl moiety is substituted by an amino, C1.3-alkylamino or di-(C1-3-alkyl)-amino group, a N-(C3.7-cycloalkyl-Cl.2-alkyl)-N-(C1.2-alkyl)-amino group wherein the cycloalkyl moiety is substituted by an amino, C1.3-alkylamino or di-(C1.3-alkyl)-amino group, a C3.7-cycloalkyl-Cl.2-alkyl-amino group wherein the cycloalkyl moiety is substituted by an amino-C1.3-alkyl, C,_3-alkylamino-C1.3-alkyl or a di-(C1.3-alkyl)amino-C1.3-alkyl group, an N-(C3.7-cycloalkyl-C1.2-alkyl)-N-(C,.2-alkyl)-amino group wherein the cycloalkyl moiety is substituted by an amino-C1.3-alkyl, C1.3-alkylamino-C1.3-alkyl or a di-(C1.3-alkyl)amino-C1.3-alkyl group, an amino group substituted by the groups R15 and R16 wherein r R15 denotes a C1.3-alkyl group and R16 denotes a R17-C2.3-alkyl group, wherein the C2.3-alkyl moiety is straight-chained and may be substituted by one to four C1.3-alkyl groups, which may be identical or different, or by an aminocarbonyl, C1.2-alkyl-aminocarbonyl, di-(C1.2-al kyl)aminocarbonyl, pyrrolidin-1-yl-carbonyl, (2-cyano-pyrrolidin-l -yl)carbonyl, thiazolidin-3-yl-carbonyl, (4-cyano-thiazolidin-3-yl)carbonyl, piperidin-l-ylcarbonyl or morpholin-4-ylcarbonyl group and R17 denotes an amino, C1.3-alkylamino or di-(C1_3-alkyl)-amino group, an amino group substituted by the group R20, wherein R20 denotes an azetidin-3-yl, azetidin-2-ylmethyl, azetidin-3-ylmethyl, pyrrolidin-3-yl, pyrrolidin-2-ylmethyl, pyrrolidin-3-ylmethyl, piperidin-3-yl, piperidin-4-yl, piperidin-2-ylmethyl, piperidin-3-ylmethyl or piperidin-4-ylmethyl group, wherein the groups mentioned for R20 may each be substituted by one or two C1.3-alkyl groups, an amino group substituted by the groups R15 and R20, wherein _34-_15 and R20 are as hereinbefore defined, wherein the groups mentioned for R20 may each be substituted by one or two C1.3-alkyl groups, a R19-C3.4-alkyl group wherein the C3.4-alkyl moiety is straight-chained and may be substituted by the group R15 and may additionally be substituted by one or two C1.3-alkyl groups, wherein R15 is as hereinbefore defined and R19 denotes an amino, C1.3-alkylamino or di-(C1.3-alkyl)-amino group, a 3-amino-2-oxo-piperidin-5-yl or 3-amino-2-oxo-1 -methyl-piperidin-5-yl group, a pyrrolidin-3-yl, piperidin-3-yl, piperidin-4-yl, hexahydroazepin-3-yl or hexahydro-azepin-4-yl group, which is substituted in the 1 position by an amino, C1.3-alkylamino or di-(C1.3-alkyl)amino group, or an azetidin-2-yl-C1.2-alkyl, azetidin-3-yl-C1.2-alkyl, pyrrolidin-2-yl-C,_2-alkyl, pyrrolidin-3-yl, pyrrolidin-3-yl-C1.2-alkyl, piperidin-2-yl-C1.2-alkyl, piperidin-3-yl, piperidin-3-yl-C1.2-alkyl, piperidin-4-yl or piperidin-4-yl-C1.2-alkyl group, wherein the abovementioned groups may each be substituted by one or two C1_3-alkyl groups, while by the aryl groups mentioned in the definition of the groups mentioned above are meant phenyl or naphthyl groups which may be mono- or disubstituted independently of one another by Rh, while the substituents may be identical or different and Rh denotes a fluorine, chlorine, bromine or iodine atom, a trifluoromethyl, cyano, nitro, amino, C,.3-alkyl, cyclopropyl, ethenyl, ethynyl, hydroxy, C1_3-alkyloxy, difluoromethoxy or trifluoromethoxy group and unless otherwise stated, the abovementioned alkyl and alkenyl groups may be straight-chained or branched, the tautomers, enantiomers, diastereomers, mixtures thereof and the salts thereof.

A third sub-group deserving special mention relates to those compounds of general formula I wherein R1, R2 and R3 are as hereinbefore defined and R4 denotes an azetidin-1-yl or pyrrolidin-1-yl group which is substituted in the 3 position by a ReNRd group and may additionally be substituted by one or two C1.3-alkyl groups, wherein '"'"' R. denotes a hydrogen atom or a C1_3-alkyl group and Rd denotes a hydrogen atom or a C1_3-alkyl group, a piperidin-1-yl or hexahydroazepin-1-yl group which is substituted in the 3 position or in the 4 position by a ReNRd group and may additionally be substituted by one or two C1.3-alkyl groups, wherein R. and Rd are as hereinbefore defined, a 3-amino-piperidin-1 -yl group wherein the piperidin-1-yl moiety is additionally substituted by an aminocarbonyl, C1.2-alkyl-aminocarbonyl, di-(C1.2-alkyl)aminocarbonyl, pyrrolidin-1-yl-carbonyl, (2-cyano-pyrrolidin-1-yl-)carbonyl, e7 thiazolidin-3-yi-carbonyl, (4-cyano-thiazolidin-3-yl)carbonyl, piperidin-1-ylcarbonyl or morpholin-4-ylcarbonyl group, a 3-amino-piperidin-1-yl group wherein the piperidin-1-yl moiety is additionally substituted in the 4 position or in the 5 position by a hydroxy or methoxy group, a 3-amino-piperidin-1-yl group wherein the methylene group in the 2 position or in the 6 position is replaced by a carbonyl group, a piperidin-1 -yl or hexahydroazepin-1-yl group substituted in the 3 position by an amino, C1.3-alkylamino or di-(C1.3-alkyl)-amino group, wherein in each case two hydrogen atoms on the carbon skeleton of the piperidin-1-yl or hexahydroazepin-1-yl group are replaced by a straight-chain alkylene bridge, this bridge containing 2 to 5 carbon atoms if the two hydrogen atoms are located on the same carbon atom, or to 4 carbon atoms, if the hydrogen atoms are located on adjacent carbon atoms, or 1 to 4 carbon atoms, if the hydrogen atoms are located on carbon atoms separated by one atom, or 1 to 3 carbon atoms if the two hydrogen atoms are located on carbon atoms separated by two atoms, an azetidin-1-yl, pyrrolidin-1-yl, piperidin-1-yl or hexahydroazepin-1-yl group which is substituted by an amino-C1.3-alkyl, C1.3-alkylamino-Cl.3-alkyl or a di-(C1.3-alkyl)-amino-Cl.3-alkyl group, a C3.7-cycloalkyl group which is substituted by an amino, C1.3-alkylamino or di-(C1.3-alkyl)-amino group, a C3_7-cycloalkyl group which is substituted by an amino-C1.3-alkyl, C1.3-alkylamino-C1.3-alkyl or a di-(C1.3-alkyl)amino-C1.3-alkyl group, a C3.7-cycloalkyl-C1_2-alkyl group wherein the cycloalkyl moiety is substituted by an amino, C1.3-alkylamino or di-(C1.3-alkyl)-amino group, a C3.7-cycloalkyl-Cl.2-alkyl group wherein the cycloalkyl moiety is substituted by an amino-C1-3-alkyl, C1.3-alkylamino-Cl.3-alkyl or a di-(C1.3-alkyl)amino-Cl.3-alkyl group, a C3_,-cycloalkylamino group wherein the cycloalkyl moiety is substituted by an amino, C1.3-alkylamino or di-(C1.3-alkyl)-amino group, wherein the two nitrogen atoms at the cycloalkyl moiety are separated from one another by at least two carbon atoms, a N-(C3_7-cycloalkyl)-N-(C1.3-alkyl)-amino group wherein the cycloalkyl moiety is substituted by an amino, C1.3-alkylamino or di-(C1.3-alkyl)-amino group, wherein the two nitrogen atoms at the cycloalkyl moiety are separated from one another by at least two carbon atoms, a C3_rcycloalkylamino group wherein the cycloalkyl moiety is substituted by an amino-Cl.3-alkyl, C1.3-alkylamino-C1.3-alkyl or a di-(C,.3-alkyl)amino-C,.3-alkyl group, a N-(C3.7-cycloalkyl)-N-(C,.3-alkyl)-amino group wherein the cycloalkyl moiety is substituted by an amino-C1.3-alkyl, C1.3-alkylamino-C,.3-alkyl or a di-(C1.3-alkyl)amino-C,.3-alkyl group, a C3.7-cycloalkyl-C,.2-alkyl-amino group wherein the cycloalkyl moiety is substituted by an amino, C1.3-alkylamino or di-(C7.3-alkyl)-amino group, a N-(C3.7-cycloalkyl-C1.2-alkyl)-N-(C,.2-alkyl)-amino group wherein the cycloalkyl moiety is substituted by an amino, C1.3-alkylamino or di-(C1.3-alkyl)-amino group, a C3.7-cycloalkyl-C,.2-alkyl-amino group wherein the cycloalkyl moiety is substituted by an amino-C1.3-alkyl, C,_3-alkylamino-C7.3-alkyl or a di-(C1.3-alkyl)amino-C,.3-alkyl group, a N-(C3.7-cycloalkyl-C7.2-alkyl)-N-(C1 2-alkyl)-amino group wherein the cycloalkyl moiety is substituted by an amino-C13-alkyl, C,_3-alkylamino-C,.3-alkyl or a di-(C,.3-alkylamino-Cl.3-alkyl group, an amino group substituted by the groups R15 and R16 wherein R15 denotes a C7.4-alkyl group and R16 denotes a R17-C2.3-alkyl group, wherein the C2.3-alkyl moiety is straight-chained and may be substituted by one to four C1.3-alkyl groups, which may be identical or different, or may be substituted by an aminocarbonyl, C,.2-alkyl-aminocarbonyl, di-(C,.2-alkyl)aminocarbonyl, pyrrolidin-1-yi-carbonyl, (2-cyano-pyrrolidin-1-yl-)carbonyl, thiazolidin-3-yl-carbonyl, (4-cyano-thiazolidin-3-yl)carbonyl, piperidin-1-ylcarbonyl or morpholin-4-ylcarbonyl group and R 17 denotes an amino, C1.3-alkylamino or di-(C1.3-alkyl)-amino group, an amino group substituted by the group R20, wherein R20 denotes an azetidin-3-yl, azetidin-2-ylmethyl, azetidin-3-ylmethyl, pyrrolidin-3-yl, pyrrolidin-2-ylmethyl, pyrrolidin-3-ylmethyl, piperidin-3-yl, piperidin-4-yl, piperidin-2-ylmethyl, piperidin-3-ylmethyl or piperidin-4-ylmethyl group, wherein the groups mentioned for R20 may each be substituted by one or two C1.3-alkyl groups, an amino group substituted by the groups R15 and R20 wherein R15 and R20 are as hereinbefore defined, wherein the groups mentioned for R20 may each be substituted by one or two C1.3-alkyl groups, an R19-C3.4-alkyl group wherein the C3_4-alkyl moiety is straight-chained and may be substituted by the group R15 and may additionally be substituted by one or two C1.3-alkyl groups, wherein R15 is as hereinbefore defined and R19 denotes an amino, C1.3-alkylamino or di-(C1.3-alkyl)-amino group, a 3-amino-2-oxo-piperidin-5-yl or 3-amino-2-oxo-1 -methyl-piperidin-5-yl group, a pyrrolidin-3-yi, piperidin-3-yi, piperidin-4-yl, hexahydroazepin-3-yl or hexahydroazepin-4-yl group, which is substituted in the 1 position by an amino, C1.3-alkylamino or di-(C1.3-alkyl)amino group, or an azetidin-2-yl-C1.2-alkyl, azetidin-3-yl-C1.2-alkyl, pyrrolidin-2-yl-C,.2-alkyl, pyrrolidin-3-yl, pyrrolidin-3-yl-C1.2-alkyl, piperidin-2-yl-C1.2-alkyl, piperidin-3-yl, piperidin-3-yl-C1.2-alkyl, piperidin-4-yl or pipe ridin-4-yl-C1.2-alkyl group, wherein the abovementioned groups may each be substituted by one or two C1.3-alkyl groups, the tautomers, enantiomers, diastereomers, mixtures thereof and the salts thereof.
Preferred compounds of the above general formula I are those wherein R1 denotes a hydrogen atom, a C,_6-alkyl group, a C3.6-alkenyl group, I
a C3-4-alkenyl group which is substituted by a C1.2-alkyloxy-carbonyl group, a C3_6-alkynyl group, a C3.6-cycloalkyl-C1 3-alkyl group, a phenyl group which may be substituted by a fluorine, chlorine or bromine atom or by a methyl, trifluoromethyl, hydroxy or methoxy group, a phenyl-C1.4-alkyl group wherein the phenyl moiety is substituted by R10 to R12, wherein R10 denotes a hydrogen atom, a fluorine, chlorine or bromine atom, a C1.4-alkyl, trifluoromethyl, hydroxymethyl, C3.6-cycloalkyl, ethynyl or phenyl group, a hydroxy, Ct_4-alkyloxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, phenoxy, benzyloxy, 2-propen-1-yloxy, 2-propyn-1-yloxy, cyano-C1.2-alkyloxy, Ct_2-al kylsulphonyloxy, phenylsulphonyloxy, carboxy-C1.
3-alkyloxy, C1.3-alkyloxy-carbonyl-C1.3-alkyloxy, aminocarbonyl-C1.3-alkyloxy, C1.2-alkyl-aminocarbonyl-Cl.3-alkyloxy, di-(C1.2-alkyl)aminocarbonyl-C1-3-alkyloxy, pyrrolidin-1-yl-carbonyl-C1.3-alkyloxy, piperidin-1-ylcarbonyl-C1-3-alkyloxy, morpholin-4-ylcarbonyl-Cl.3-alkyloxy, methylsulphanylmethoxy, methylsulphinylmethoxy, methylsuiphonylmethoxy, C3-6-cycloalkyloxy or Ca.-cycloalkyl-C,_2-alkyloxy group, a carboxy, C,_3-alkyloxycarbonyl, carboxy-CI_3-alkyl, C,_3-alkyloxy-carbonyl-C1.3-alkyl, aminocarbonyl, C,_2-alkylaminocarbonyl, di-(C,_2-alkyl)aminocarbonyl, morpholin-4-ylcarbonyl or cyano group, a nitro, amino, C,.2-alkylamino, di-(C1_2-alkyl)amino, cyano-C1.2-alkylamino, [N-(cyano-Ci_2-alkyl)-N-C,_2-alkyl-amino], C,_2-alkyloxy-carbonyl-C,_2-alkylamino, Ci_2-alkylcarbonylamino, Ci_2-alkyloxy-carbonylamino, C1.3-alkylsulphonylamino, bis-(C1-2-alkylsulphonyl)-amino, aminosuiphonylamino, C1.2-alkylamino-sulphonylamino, di-(C1.2-alkylamino-sulphonylamino, morpholin-4-yl-sulphonylamino, (C1.2-alkylamino)thiocarbonylamino, (C1.2-alkyloxy-carbonylami no)carbonylamino, aminocarbonylamino, C1.2-alkylaminocarbonylamino, di-(C1.2-alkyl)aminocarbonylamino or morpholin-4-ylcarbonylamino group, a 2-oxo-imidazolidin-1-yl, 3-methyl-2-oxo-imidazolidin-1-yl, 2,4-dioxo-imidazolidin-1-yl, 3-methyl-2,4-dioxo-imidazolidin-1-yl, 2,5-dioxo-imidazolidin-1-y1, 3-methyl-2,5-dioxo-imidazolidin-1-yl, 2-oxo-hexahydropyrimidin-1-yl or 3-methyl-2-oxo-hexahydropyrimidin-1-yl group, or a C1.2-alkylsulphanyl, C1.2-alkylsulphinyl, C1.2-alkylsulphonyl, aminosulphonyl, C1.2-alkylaminosulphonyl or di-(C1-2-alkyl)aminosulphonyl group, and R11 and R12, which may be identical or different, denote a hydrogen, fluorine, chlorine or bromine atom or a methyl, cyano, trifluoromethyl or methoxy group, or, R" together with R12, if they are bound to adjacent carbon atoms, also denote a methylenedioxy, difluoromethylenedioxy, 1,3-propylene or 1,4-butylene group, a phenyl-C1.3-alkyl group wherein the alkyl moiety is substituted by a carboxy, C1.2-alkyloxy-carbonyl, aminocarbonyl, C1.2-alkylaminocarbonyl or di-(C1.2-alkyl)amino-carbonyl group, a phenyl-C2.3-alkenyl group, wherein the phenyl moiety may be substituted by a fluorine, chlorine or bromine atom or by a methyl, trifluoromethyl or methoxy group, a phenyl-(CH2)m-A-(CH2)n group wherein the phenyl moiety is substituted by R10 to R12, wherein R10 to R'2 are as hereinbefore defined and A denotes a carbonyl, hydroxyiminomethylene or C,.2-alkyloxyiminomethylene group, m denotes the number 0 or 1 and n denotes the number 1 or 2, a phenylcarbonylmethyl group wherein the phenyl moiety is substituted by R10 to R12, wherein R10 to R12 are as hereinbefore defined and the methyl moiety is substituted by a methyl or ethyl group, a phenylcarbonylmethyl group wherein two adjacent hydrogen atoms of the phenyl moiety are replaced by a -0-CO-NH, -NH-CO-NH, -N=CH-NH, -N=CH-0 or -O-CH2-CO-NH- bridge, wherein the abovementioned bridges may be substituted by one or two methyl groups, a phenyl-(CH2)m-B-(CH2)n group wherein the phenyl moiety is substituted by R10 to R12, wherein R10 to R12, m and n are as hereinbefore defined and B denotes a methylene group which is substituted by a hydroxy or C,.2-alkyloxy group and is optionally additionally substituted by a methyl group, a naphthylmethyl or naphthylethyl group, wherein the naphthyl moiety is substituted in each case by R10 to R12, wherein R10 to R12 are as hereinbefore defined, a [1,4]naphthoquinon-2-yl, chromen-4-on-3-yl or 1-oxoindan-2-yl group, a heteroaryl-Cl.3-alkyl group, wherein by the term heteroaryl is meant a pyrrolyl, imidazolyl, triazolyl, furanyl, thienyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, benzimidazolyl, 2,3-dihydro-2-oxo-1 H-benzimidazolyl, indazolyl, benzofuranyl, 2,3-dihydrobenzofuranyl, benzoxazolyl, dihydro-2-oxo-benzoxazolyl, benzisoxazolyl, benzothiophenyl, benzothiazolyl, benzoisothiazolyl, quinolinyl, 1,2-dihydro-2-oxo-quinolinyl, isoquinolinyl, 1,2-dihydro-1-oxo-isoquinolinyl, cinnolinyl, quinazolinyl, 1,2-dihydro-2-oxo-quinazolinyl, 1,2-dihydro-1-oxo-phthalazin-4-yl, cumarinyl or 3,4-dihydro-3-oxo-2H-benzo[1,4]oxazinyl group, wherein the abovementioned heteroaryl groups may be substituted at carbon atoms by a fluorine, chlorine or bromine atom, by a methyl, trifluoromethyl, cyano, aminocarbonyl, aminosulphonyl, methylsuiphonyl, nitro, amino, acetylamino, methylsulphonylamino, methoxy, difluoromethoxy or trifluoromethoxy group and the imino groups of the abovementioned heteroaryl groups may be substituted by methyl or ethyl groups, a furanyl-A-CH2, thienyl-A-CH2, thiazolyl-A-CH2 or pyridyl-A-CH2 group, wherein A is as hereinbefore defined, a furanyl-B-CH2, thienyl-B-CH2, thiazolyl-B-CH2 or pyridyl-B-CH2 group, wherein B is as hereinbefore defined, a C1.4-alkyl-A-(CH2)õ group, wherein A and n are as hereinbefore defined, a C3_6-cycloalkyl-(CH2)m-A-(CH2)n group, wherein A, m and n are as hereinbefore defined, a C3.6-cycloalkyl-(CH2)m-B-(CH2)õ group, wherein B, m and n are as hereinbefore defined, an R21-A-(CH2)õ group wherein R21 denotes a C,_2-alkyloxycarbonyl, aminocarbonyl, C,_2-alkylaminocarbonyl, di-(C,_2-al kyl)aminocarbonyl, pyrrolidin-1-yl-carbonyl, piperidin-1-yl-carbonyl or morpholin-4-yl-carbonyl group and A and n are as hereinbefore defined, a phenyl-D-C,_3-alkyl group wherein the phenyl moiety is optionally substituted by a fluorine, chlorine or bromine atom, a methyl, trifluoromethyl or methoxy group and D
denotes an oxygen or sulphur atom, a sulphinyl or sulphonyl group, a C1_4-alkyl group substituted by a group Ra, wherein Ra denotes a cyano, carboxy, C,_3-alkyloxy-carbonyl, aminocarbonyl, C,.2-alkyl-aminocarbonyl, di-(C,.2-alkyl)aminocarbonyl, pyrrolidin-1-yl-carbonyl, piperidin-l-ylcarbonyl or morpholin-4-ylcarbonyl group, a C2.4-alkyl group substituted by a group Rb, wherein Rb denotes a hydroxy, C,_3-alkyloxy, amino, C,_3-alkylamino, di-(C,_3-alkyl)-amino, pyrrolidin-1-yl, piperidin-1-yl, morpholin-4-yl, piperazin-1-yl, 4-methyl-piperazin-1-yl or 4-ethyl-piperazin-1-yl group and is isolated by at least two carbon atoms from the cyclic nitrogen atom in the 1 position of the xanthine skeleton, or an amino or benzoylamino group, R2 denotes a hydrogen atom, a C1.6-alkyl group, a C2.4-alkenyl group, a C3.4-alkynyl group, a C3.6-cycloalkyl group, a C3_6-cycloalkyl-Cl.3-alkyl group, a tetrahydrofuran-3-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, tetrahydrofuranylmethyl or tetrahydropyranylmethyl group, a phenyl group which is optionally substituted by a fluorine, chlorine or bromine atom or by a methyl, trifluoromethyl, hydroxy, methoxy, difluoromethoxy or trifluoromethoxy group, a phenyl-Cl.4-alkyl group wherein the phenyl moiety is optionally substituted by a fluorine, chlorine or bromine atom, a methyl, trifluoromethyl, dimethylamino, hydroxy, methoxy, difluoromethoxy or trifluoromethoxy group, a phenyl-C2.3-alkenyl group, wherein the phenyl moiety may be substituted by a fluorine, chlorine or bromine atom or by a methyl, trifluoromethyl or methoxy group, a phenylcarbonyl-C1.2-alkyl group wherein the phenyl moiety is optionally substituted by a fluorine, chlorine or bromine atom, a methyl, trifluoromethyl, hydroxy, methoxy, difluoromethoxy or trifluoromethoxy group, a heteroaryl-Cl.3-alkyl group, wherein the term heteroaryl is as hereinbefore defined, a furanylcarbonylmethyl, thienylcarbonylmethyl, thiazolylcarbonylmethyl or pyridylcarbonylmethyl group, a C,.4-alkyl-carbonyl-C,.2-alkyl group, a C3_6-cycloalkyl-carbonyl-C1.2-alkyl group, a phenyl-D-C,.3-alkyl group wherein the phenyl moiety is optionally substituted by a fluorine, chlorine or bromine atom, a methyl, trifluoromethyl, hydroxy, methoxy, difluoromethoxy or trifluoromethoxy group, and D is as hereinbefore defined, or a C,_4-alkyl group substituted by a group Ra, wherein Ra is as hereinbefore defined, a C2.4-alkyl group substituted by a group Rb, wherein Rb is as hereinbefore defined and is isolated by at least two carbon atoms from the cyclic nitrogen atom in the 3 position of the xanthine skeleton, R3 denotes a C2.6-alkyl group, a C3.,-alkenyl group, a C3.5-alkenyl group which is substituted by a fluorine, chlorine or bromine atom or a trifluoromethyl group, a C3.6-alkynyl group, a C1.3-alkyl group substituted by the group Rc, wherein Rc denotes a C3.6-cycloalkyl group optionally substituted by one or two methyl groups, a C5.6-cycloalkenyl group optionally substituted by one or two methyl groups, a phenyl group optionally substituted by a fluorine, chlorine, bromine or iodine atom, by a methyl, trifluoromethyl, cyano, nitro, amino, hydroxy, methoxy, difluoromethoxy or trifluoromethoxy group, a phenyl group which is substituted by two fluorine atoms, a naphthyl group or a furanyl, thienyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl or pyridyl group optionally substituted by a methyl or trifluoromethyl group, a phenyl group optionally substituted by a fluorine, chlorine or bromine atom, by a methyl, trifluoromethyl, cyano, hydroxy, methoxy, difluoromethoxy or trifluoromethoxy group, a phenyl group which is substituted by two methyl groups, a naphthyl group or a phenyl-C2.3-alkenyl group and R4 denotes a pyrrolidin-1 -yl group which is substituted in the 3 position by an amino, methylamino or dimethylamino group, an azetidin- 1 -yl group which is substituted by an aminomethyl group, a pyrrolidin-1 -yl group which is substituted by an aminomethyl group, a piperidin-1 -yl group which is substituted in the 3 position or in the 4 position by an amino, methylamino, dimethylamino or [(2-cyano-pyrrolidin-1-yl-)carbonylmethyl]-amino group, wherein the piperidin-1-yl moiety may additionally be substituted by a methyl or ethyl group, a 3-amino-piperidin-1-yl group wherein the piperidin-1-yl moiety is additionally substituted by an aminocarbonyl, C1.2-alkyl-aminocarbonyl, di-(C,.2-alkyl)aminocarbonyl, pyrrolidin-1-yl-carbonyl, (2-cyano-pyrrolidin-1-yl-)carbonyl, thiazolidin-3-yl-carbonyl, (4-cyano-thiazolidin-3-yl)carbonyl, piperidin-1-ylcarbonyl or morpholin-4-ylcarbonyl group, a 3-amino-piperidin-1-yl group wherein the piperidin-1-yl moiety in the 4 position or in the 5 position is additionally substituted by a hydroxy or methoxy group, a 3-amino-piperidin-1 -yl group wherein the methylene group in the 2 position or in the 6 position is replaced by a carbonyl group, a 3-amino-piperidin-1 -yl group wherein a hydrogen atom in the 2 position together with a hydrogen atom in the 5 position is replaced by a -CH2-CH2- bridge, a 3-amino-piperidin-1 -yl group wherein a hydrogen atom in the 2 position together with a hydrogen atom in the 6 position is replaced by a -CH2-CH2- bridge, a 3-amino-piperidin-1 -yl group wherein a hydrogen atom in the 4 position together with a hydrogen atom in the 6 position is replaced by a -CH2-CH2- bridge, a piperidin-1-yl group which is substituted by an aminomethyl group, a piperidin-3-yl or piperidin-4-yl group, a piperidin-3-yl or piperidin-4-yl group which is substituted in the 1 position by an amino group, a hexahydroazepin-1-yl group which is substituted in the 3 position or in the position by an amino group, a piperazin-1 -yl or [1,4]diazepan-1-yl group optionally substituted at the carbon skeleton by one or two methyl groups, a 3-imino-piperazin-1-yl, 3-imino-[1,4]diazepan-1-yl or 5-imino-[1,4]diazepan-1-yl group, a [1,4]diazepan-1-yl group, which is substituted in the 6 position by an amino group, a C3.6-cycloalkyl-amino group wherein the cycloalkyl moiety is substituted by an amino, methylamino or dimethylamino group, wherein the two nitrogen atoms are isolated from one another at the cycloalkyl moiety by at least two carbon atoms, an N-(C3_6-cycloalkyl)-N-(C1-2-alkyl)-amino group wherein the cycloalkyl moiety is substituted by an amino, methylamino or dimethylamino group, wherein the two nitrogen atoms are isolated from one another at the cycloalkyl moiety by at least two carbon atoms, a C3.6-cycloalkyl-amino group wherein the cycloalkyl moiety is substituted by an aminomethyl or aminoethyl group, an N-(C3.6-cycloalkyl)-N-(C1.2-alkyl)-amino group wherein the cycloalkyl moiety is substituted by an aminomethyl or aminoethyl group, a C3_6-cycloalkyl-C1.2-alkyl-amino group wherein the cycloalkyl moiety is substituted by an amino, aminomethyl or aminoethyl group, an N-(C3.6-cycloalkyl-C1.2-alkyl)-N-(C1.2-alkyl)-amino group wherein the cycloalkyl moiety is substituted by an amino, aminomethyl or aminoethyl group, an amino group substituted by the groups R15 and R16 wherein R15 denotes a C1.4-alkyl group and R16 denotes a 2-aminoethyl, 2-(methylamino)ethyl or 2-(dimethylamino)ethyl group, wherein the ethyl moiety may in each case be substituted by one or two methyl or ethyl groups or by an aminocarbonyl, C1.2-alkyl-aminocarbonyl, di-(C1.2-alkyl)aminocarbonyl, pyrrolidin-1-yl-carbonyl, piperidin-l-ylcarbonyl or morpholin-4-ylcarbonyl group, an amino group wherein the nitrogen atom is substituted by a pyrrolidin-3-yl, piperidin-3-yl, piperidin-4-yl, pyrrolidin-2-ylmethyl, pyrrolidin-3-ylmethyl, piperidin-2-ylmethyl, piperidin-3-ylmethyl or piperidin-4-ylmethyl group, a C1_2-alkylamino group wherein the nitrogen atom is substituted by a pyrrolidin-3-yl, piperidin-3-yl, piperidin-4-yl, pyrrolidin-2-ylmethyl, pyrrolidin-3-ylmethyl, piperidin-2-ylmethyl, piperidin-3-ylmethyl or pipe ridi n-4-yl methyl group, a 3-amino-propyl, 3-methylamino-propyl or 3-dimethylamino-propyl group wherein the propyl moiety may be substituted by one or two methyl groups, a 4-amino-butyl, 4-methylamino-butyl or 4-dimethylamino-butyl group wherein the butyl moiety may be substituted by one or two methyl groups, a C1.2-alkyl group which is substituted by a 2-pyrrolidinyl, 3-pyrrolidinyl, 2-piperidinyl, 3-piperidinyl or 4-piperidinyl group, a 3-amino-2-oxo-piperidin-5-yl or 3-amino-2-oxo-1-methyl-piperidin-5-yl group, a C3.6-cycloalkyl group which is substituted by an amino, aminomethyl or aminoethyl group or .50-a Cis-cycloalkyl-C,_2-alkyl group wherein the cycloalkyl moiety is substituted by an amino, aminomethyl or aminoethyl group, while, unless otherwise stated, the abovementioned alkyl, alkenyl and alkynyl groups may be straight-chain or branched, with the proviso that the compounds wherein R' denotes a hydrogen atom, a methyl, propyl, 2-hydroxypropyl, aminocarbonyl-methyl or benzyl group, R2 denotes a methyl group, R3 denotes a C,_5-alkyl group, a benzyl group optionally substituted by a fluorine, chlorine or bromine atom or by a methyl group, a 1-phenylethyl or 2-phenylethyl group, a 2-propen-1-yi, 2-buten-1 -yl, 3-chloro-2-buten-1 -yl or 2-methyl-2-propen-1 -yl group and R4 denotes a piperazin-1 -yl group, are excluded, the tautomers, enantiomers, diastereomers, mixtures thereof and the salts thereof.
A sub-group of the preferred compounds of formula I deserving special mention relates to those compounds of general formula I wherein R' to R4 are as hereinbefore defined, with the additional proviso that the compounds wherein denotes an optionally substituted piperazin-1 -yl or [1,4]diazepan-1-yl group are excluded, the tautomers, enantiomers, diastereomers, mixtures thereof and the salts thereof.

A second sub-group of the preferred compounds of formula I deserving special mention relates to those compounds of general formula I wherein R1 denotes a hydrogen atom, a C1-4-alkyl group, a C3.5-alkenyl group, a 2-propen-1-yl group which is substituted by a methoxycarbonyl group, a C3.5-alkynyl group, a phenyl-C1.4-alkyl group wherein the phenyl moiety is substituted by R10 to R12, wherein R10 denotes a hydrogen atom, a fluorine, chlorine or bromine atom, a methyl, ethyl, trifluoromethyl or ethynyl group, a hydroxy, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, phenoxy, benzyloxy, 2-propen-1-yloxy, 2-propyn-1-yloxy, cyano-Cl.2-alkyloxy, C1.2-alkyl-sulphonyloxy, phenylsulphonyloxy, carboxy-C1.2-alkyloxy, C1.2-alkyloxy-carbonyl-Cl.2-alkyloxy, aminocarbonyl-C1.2-alkyloxy, C1.2-alkyl-aminocarbonyl-Cl-2-alkyloxy, di-(C1-2-alkyl)aminocarbonyl-C1.2-alkyloxy, pyrrolidin-1-ylcarbonyl-Cl-2-alkyloxy, piperidin-1-ylcarbonyl-C1.2-alkyloxy, morpholin-4-ylcarbonyl-C1.2-alkyloxy group, a carboxy, C1.2-alkyloxy-carbonyl, aminocarbonyl, C1.2-alkylaminocarbonyl, di-(C1.2-alkyl)aminocarbonyl, morpholin-4-ylcarbonyl or cyano group, a nitro, amino, C1.2-alkylamino, di-(C1.2-alkyl)amino, cyano-C1.2-alkylamino, [N-(cyano-Cl.2-alkyl)-N-methyl-amino], C1.2-alkyloxy-carbonyl-C1.2-alkylamino, C1 _2-alkyl-carbonylamino, C1.2-alkyloxy-carbonylamino, C1.2-alkylsulphonylamino, bis-(C1.2-alkylsulphonyl)-amino, aminosulphonylamino, C1_2-alkylamino-sulphonylamino, di-(C1.2-alkyl)amino-sulphonylamino, morpholin-4-yl-sulphonylamino, (C1.2-alkylamino)thiocarbonylamino, (C1.2-al kyloxy-carbonylamino)carbonylamino, aminocarbonylamino, C1.2-alkylaminocarbonylamino, di-(C,.2-alkyl)aminocarbonylamino or morpholin-4-yl-carbonylamino group, a 2-oxo-imidazolidin-1-yl, 3-methyl-2-oxo-imidazolidin-1-yl, 2,4-dioxo-imidazolidin-1-yl, 3-methyl-2,4-dioxo-imidazolidin-1-yl, 2,5-dioxo-imidazolidin-1-yl, 3-methyl-2,5-dioxo-imidazolidin-1-yl, 2-oxo-hexahydropyrimidin-1 -yl or methyl-2-oxo-hexahydropyrimidin-1-yl group, or a C1.2-alkylsulphanyl, C1.2-alkylsulphinyl, C1.2-alkylsulphonyl, aminosulphonyl, C1_2-alkylaminosulphony[ or di-(C1_2-alkyl)aminosulphonyl group, and R" and R12, which may be identical or different, denote a hydrogen, fluorine, chlorine or bromine atom or a methyl, cyano or methoxy group, or, R" together with R12, if they are bound to adjacent carbon atoms, also denote a methylenedioxy group, a phenylmethyl group wherein the methyl moiety is substituted by a carboxy, methoxycarbonyl or aminocarbonyl group, a 2-phenylethyl group wherein the ethyl moiety is substituted by a carboxy, methoxycarbonyl or aminocarbonyl group, a 2-phenylethyl group wherein the ethyl moiety is substituted in the 2 position by a hydroxy, methoxy, hydroxyimino or methoxyimino group, a 2-phenylethyl group wherein the ethyl moiety is substituted in the 2 position by a hydroxy group and a methyl group, a phenylcarbonylmethyl group wherein the phenyl moiety is substituted by R10 to R12, wherein R10 to R12 are as hereinbefore defined, a 1 -(phenylcarbonyl) ethyl or 2-(phenylcarbonyl)ethyl group, a 2-phenylethenyl group, a phenylsuiphanylmethyl or phenylsuiphinylmethyl group, a 2-(phenyloxy)ethyl group, a naphthylmethyl or naphthylethyl group, wherein the naphthyl moiety may be substituted in each case by a methyl, nitro, amino, acetylamino, methylsuiphonylamino, cyano, aminocarbonyl or aminosulphonyl group, a [1,4]naphthoquinon-2-yl, chromen-4-on-3-yl or 1-oxoindan-2-yl group an oxazolylmethyl, isoxazolylmethyl, thiazolylmethyl, pyridylmethyl, benzo-furanylmethyl, 2,3-dihydrobenzofuranylmethyl, benzo[d]isoxazolylmethyl, benzo-[d]isothiazolylmethyl, (1H-indazol-3-yl)methyl, quinolinylmethyl, (1,2-dihydro-2-oxo-quinolin-4-yl)methyl, isoquinolinylmethyl, (1,2-dihydro-l -oxo-isoquinolin-4-yl)methyl, cinnolinylmethyl, quinazolinylmethyl, (1,2-dihydro-2-oxo-quinazolin-4-yl)methyl, (1,2-dihydro-1-oxo-phthalazin-4-yl)methyl or cumarinylmethyl group, wherein the heterocyclic moiety may be substituted by a methyl group in each case, a quinolinylmethyl or isoquinolinylmethyl group, wherein the heterocyclic moiety is substituted in each case by a cyano, nitro, amino, acetylamino, methylsulphonylamino, aminocarbonyl or aminosulphonyl group, a pyrrolylethyl, triazolylethyl, thienylethyl, thiazolylethyl or pyridylethyl group, wherein the heterocyclic moiety may be substituted in each case by a methyl group, a furanylcarbonylmethyl, thienylcarbonylmethyl, thiazolylcarbonylmethyl or pyridylcarbonylmethyl group, a methyl group which is substituted by a cyclopropyl, cyano, carboxy, aminocarbonyl or methoxycarbonyl group, an ethyl group which is substituted in the 2 position by a hydroxy, methoxy, dimethylamino, carboxy or methoxycarbonyl group, or a propyl group which is substituted in the 3 position by a hydroxy, dimethylamino, carboxy or methoxycarbonyl group, a 2-oxopropyl group or an amino or benzoylamino group, R2 denotes a hydrogen atom, a C,-6-alkyl group, an ethenyl group, a 2-propen-1-yl or 2-propyn-1-yl group, a C3_6-cycloalkyl group, a tetrahydrofuran-3-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, tetrahydro-furanylmethyl or tetrahydropyranylmethyl group, a phenyl group, a phenyl-C,4-alkyl group, wherein the phenyl moiety may be substituted by a fluorine or chlorine atom, a methyl, dimethylamino, hydroxy, methoxy or trifluoromethoxy group, a phenylcarbonylmethyl group, wherein the phenyl moiety may be substituted by a fluorine or chlorine atom, a hydroxy, methoxy or trifluoromethoxy group, a 2-phenylethenyl group, a 2-(phenyloxy)ethyl group, a pyridylmethyl or pyridylethyl group, a methyl group which is substituted by a C3-6-cycloalkyl, cyano, carboxy or methoxy-carbonyl group, or an ethyl group which is substituted in the 2 position by a C3.6-cycloalkyl, cyano, carboxy, methoxycarbonyl, hydroxy, methoxy or dimethylamino group, or a propyl group which is substituted in the 3 position by a Cwcycloalkyl, cyano, carboxy, methoxycarbonyl, hydroxy, methoxy or dimethylamino group, R3 denotes a C4.6-alkenyl group, a 1-cyclopenten-1-ylmethyl or 1-cyclohexen-1-ylmethyl group, a 1 -cyclopenten-1 -ylmethyl group wherein the 1-cyclopenten-1-yi moiety is substituted by a methyl group, a 2-propyn-1-yl, 2-butyn-1-yl or 2-pentyn-1-yl group, a phenyl group which may be substituted by a fluorine atom or a cyano, methyl-methoxy or trifluoromethyl group, a phenyl group which is substituted by two methyl groups, a benzyl group wherein the phenyl moiety may be substituted by one or two fluorine atoms, a chlorine, bromine or iodine atom, or a methyl, methoxy, cyano, nitro or amino group, a furanylmethyl or thienylmethyl group, a cyclopropylmethyl group or a cyclopropylmethyl group wherein the cyclopropyl moiety is substituted by a methyl group, and R4 denotes a piperidin-1-yl group which is substituted in the 3 position by an amino group, wherein the piperidin-1 -yl moiety may additionally be substituted by a methyl group, a 3-amino-piperidin-1-yl group wherein the piperidin-1-yl moiety is additionally substituted by an aminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, pyrrolidi n-1-yl-carbonyl, (2-cyano-pyrrolidin-1-yl-)carbonyl, thiazolidin-3-yl-carbonyl, (4-cyano-thiazolidin-3-yl)carbonyl, piperidin-1-ylcarbonyl or morpholin-4-ylcarbonyl group, a 3-amino-piperidin-1-yl group wherein the piperidin-1-yl moiety in the 4 position or in the 5 position is additionally substituted by a hydroxy or methoxy group, a 3-amino-piperidin-1-yl group wherein a hydrogen atom in the 2 position together with a hydrogen atom in the 5 position is replaced by a -CH2-CH2-bridge, a hexahydroazepin-1-yl group which is substituted in the 3 position by an amino group, a 3-amino-2-oxo-piperidin-5-yi or 3-amino-2-oxo-1-methyl-piperidin-5-yi group, a [1,4]diazepan-1-yl group, which is substituted in the 6 position by an amino group, a cyclohexyl group which is substituted in the 3 position by an amino group, a 2-amino-cyclohexylamino group, or an amino group substituted by the groups R15 and R16 wherein R15 denotes a methyl or ethyl group and R16 denotes a 2-aminoethyl group, wherein the ethyl moiety may be substituted by one or two methyl groups or by an aminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl or pyrrolidin-1-ylcarbonyl group, unless otherwise stated, the abovementioned alkyl and alkenyl groups may be straight-chained or branched, the tautomers, enantiomers, diastereomers, mixtures thereof and the salts thereof.
A third sub-group of the preferred compounds of formula I deserving special mention relates to those compounds of general formula I wherein R1, R2 and R3 are as hereinbefore defined and R4 denotes a piperidin-1-yl group which is substituted in the 3 position by an amino group, wherein the piperidin-1 -yl moiety may additionally be substituted by a methyl group, a 3-amino-piperidin-1-yl group wherein the piperidin-1-yl moiety is additionally substituted by an aminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, pyrrolidin-1-yl-carbonyl, (2-cyano-pyrrolidin-1-yl-)carbonyl, thiazolidin-3-yl-carbonyl, (4-cyano-thiazolidin-3-yl)carbonyl, piperidin-l-ylcarbonyl or morpholin-4-ylcarbonyl group, a 3-amino-piperidin-1-yl group wherein the piperidin-1-yl moiety is additionally substituted in the 4 position or in the 5 position by a hydroxy or methoxy group, a 3-amino-piperidin-1-yl group wherein a hydrogen atom in the 2 position together with a hydrogen atom in the 5 position is replaced by a -CH2-CH2-bridge, a hexahydroazepin-1-yl group which is substituted in the 3 position by an amino group, a 3-amino-2-oxo-piperidin-5-yl or 3-amino-2-oxo-1 -methyl-piperidin-5-yl group, a cyclohexyl group which is substituted in the 3 position by an amino group, a 2-amino-cyclohexylamino group, or an amino group substituted by the groups R15 and R16, wherein R15 denotes a methyl or ethyl group and _59-R 16 denotes a 2-aminoethyl group, wherein the ethyl moiety may be substituted by one or two methyl groups or by an aminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl or pyrrolidin-1-ylcarbonyl group, unless otherwise stated, the abovementioned alkyl- and alkenyl groups may be straight-chained or branched, the tautomers, enantiomers, diastereomers, mixtures thereof and the salts thereof.
Particularly preferred compounds of the above general formula I are those wherein R1 denotes a hydrogen atom, a C,_4-alkyl group, a C3_5-alkenyl group, a 2-propen-1 -yl group which is substituted by a methoxycarbonyl group, a C3.5-alkynyl group, a phenyl group, a phenyl-C,_4-alkyl group wherein the phenyl moiety may be substituted by one or two fluorine atoms, one or two chlorine atoms, a bromine atom, one to three methyl groups, a butyl, trifluoromethyl, hydroxy, methoxy, nitro, amino, carboxy or ethoxycarbonyl group, a 2-phenylethyl group wherein the ethyl moiety is substituted in the 2 position by a hydroxy, methoxy or hydroxyimino group, a phenylcarbonylmethyl group wherein the phenyl moiety may be substituted by a fluorine atom or by a methyl, aminocarbonyl, aminosulphonyl, cyano, hydroxy, methoxy, phenoxy, benzyloxy, 2-propen-1-yloxy, 2-propyn-1-yloxy, cyanomethoxy, (methoxycarbonyl)methoxy, (aminocarbonyl)methoxy, (methylaminocarbonyl)-methoxy, (dimethylaminocarbonyl)methoxy, methylsulphonyloxy, phenylsuiphonyloxy, nitro, amino, (methoxycarbonyl)methylamino, acetylamino, methoxycarbonylamino, methylsulphonylamino, bis-(methylsulphonyl)-amino, aminocarbonylamino, dimethylaminocarbonylamino, (methylamino)thiocarbonylamino, (ethoxy carbonylamino)carbonylamino or cyanomethylamino group, a phenylcarbonylmethyl group wherein the phenyl moiety is substituted by two methoxy groups or by a bromine atom and by a dimethylamino group, a 2-(phenylcarbonyl)ethyl group, a 2-phenylethenyl group, a 2-(phenoxy) ethyl group, a phenylsulphanylmethyl or phenylsul phi nyl methyl group, a naphthylmethyl or naphthylethyl group, an isoxazolylmethyl, thiazolylmethyl, pyridylmethyl, benzo[d]isoxazolylmethyl, benzo[d]isothiazolylmethyl, (1 H-indazol-3-yl)methyl, quinolinylmethyl or isoquinolinylmethyl group, wherein the heterocyclic moiety may in each case be substituted by a methyl group, a isoquinolinylmethyl group wherein the isoquinolinyl moiety is substituted by a nitro or amino group, a (1,2-dihydro-2-oxo-quinolin-4-yl)methyl group, a chromen-4-on-3-yl group, a pyrrolylethyl, triazolylethyl, thienylethyl, thiazolylethyl or pyridylethyl group, wherein the heterocyclic moiety may in each case be substituted by a methyl group, a thienylcarbonylmethyl group, a methyl group which is substituted by a cyclopropyl, cyano, carboxy, aminocarbonyl or methoxycarbonyl group, an ethyl group which is substituted in the 2 position by a hydroxy, methoxy, dimethylamino, carboxy or methoxycarbonyl group, or a propyl group which is substituted in the 3 position by a hydroxy, dimethylamino, carboxy or methoxycarbonyl group, a 2-oxopropyl group or an amino or benzoylamino group, R2 denotes a hydrogen atom, a C,_s-alkyl group, an ethenyl group, a 2-propen-1-yl or 2-propyn- 1 -yl group, a phenyl group, a phenyl-C1.4-alkyl group, wherein the phenyl moiety may be substituted by a fluorine atom, a methyl or methoxy group, a phenylcarbonylmethyl group, a 2-phenylethenyl group, a methyl group which is substituted by a cyclopropyl, cyano, carboxy or methoxy-carbonyl group, or an ethyl group which is substituted in the 2 position by a cyano, hydroxy, methoxy or dimethylamino group, R3 denotes a C4.6-alkenyl group, a 1-cyclopenten-1-ylmethyl or 1-cyclohexen-1-ylmethyl group, a 2-propyn-1 -yl, 2-butyn-1 -yl or 2-pentyn-1 -yl group, a phenyl group which may be substituted by a fluorine atom or a cyano, methyl or trifluoromethyl group, a phenyl group which is substituted by two methyl groups, a naphthyl group, a benzyl group wherein the phenyl moiety may be substituted by one or two fluorine atoms, an iodine atom or a cyano, nitro or amino group, a naphthylmethyl group, a 2-phenylethenyl group, a furanylmethyl or thienylmethyl group or a cyclopropylmethyl group and R4 denotes a pyrrolidin-l -yl group which is substituted in the 3 position by an amino group, an azetidin-l-yl group which is substituted by an aminomethyl group, a pyrrolidin-l-yl group which is substituted by an aminomethyl group, a piperidin-l-yl group which is substituted in the 3 position or in the 4 position by an amino, methylamino, dimethylamino or [(2-cyano-pyrrolidin-1 -yl)carbonylmethyl]-amino group, wherein the piperidin-l-yl moiety may additionally be substituted by a methyl group, a 3-amino-piperidin-1-yl group wherein the piperidin-1-yl moiety is additionally substituted by a pyrrolidin-l-yl-carbonyl group, a 3-amino-piperidin-1-yl group wherein the piperidin-1-yl moiety in the 4 position is additionally substituted by a hydroxy group, a 3-amino-piperidin-1-yl group wherein a hydrogen atom in the 2 position together with a hydrogen atom in the 5 position is replaced by a -CH2-CH2-bridge, a piperidin-1 -yl group which is substituted by an aminomethyl group, a piperidin-3-yl or piperidin-4-yl group, a 1-amino-piperidin-3-yl or 1-amino-piperidin-4-yi group, a hexahydroazepin-1 -yl group which is substituted in the 3 position or in the position by an amino group, a piperazin-1-yl or [1,4]diazepan-1-yl group, a [1,4]diazepan-1-yl group, which is substituted in the 6 position by an amino group, a 3-aminopropyl group, a cyclohexyl group which is substituted by an amino group, a 2-amino-cyclopropylamino group, a 2-amino-cyclobutylamino group, a 2-amino-cyclopentylamino or 3-amino-cyclopentylamino group, a 2-amino-cyclohexylamino, 2-(methylamino)-cyclohexylamino or 3-amino-cyclohexylamino group, an N-(2-aminocyclohexyl)-methylamino group, an amino group substituted by the groups R15 and R16 wherein R15 denotes a methyl or ethyl group and R 16 denotes a 2-aminoethyl- 2-(methylamino)ethyl or 2-(dimethylamino)ethyl group, wherein the ethyl moiety may be substituted by one or two methyl groups or by an aminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl or pyrrolidin-1-ylcarbonyl group, or an amino or methylamino group wherein the nitrogen atom is substituted by a pyrrolidin-3-yl, piperidin-3-yl, piperidin-4-yl or piperidin-2-ylmethyl group, while unless otherwise stated, the abovementioned alkyl and alkenyl groups may be straight-chain or branched, with the proviso that the compounds 3-methyl-7-(2-buten-1-yl)-8-(piperazin-1-yl)-xanthine, 3-methyl-7-(2-methyl-2-propen-1 -yl)-8-(piperazin-1 -yl)-xanthine, 3-methyl-7-benzyl-8-(piperazin-1-yl)-xanthine, 1,7-dibenzyl-3-methyl-8-(piperazin-1-yl)-xanthine and 1,3-dimethyl-7-(4-fluorobenzyl)-8-(piperazin-1-yl)-xanthine are excluded, the tautomers, enantiomers, diastereomers, mixtures thereof and the salts thereof.
A sub-group of the particularly preferred compounds of formula I deserving special mention relates to those compounds of general formula I wherein R1 to R4 are as hereinbefore defined, with the additional proviso that the compounds wherein denotes an optionally substituted piperazin-1 -yl or [1,4]diazepan-1-yl group are excluded, the tautomers, enantiomers, diastereomers, mixtures thereof and the salts thereof.

A second sub-group of the particularly preferred compounds of formula I
deserving special mention relates to those compounds of general formula I wherein R1 denotes a hydrogen atom, a C1_4-alkyl group, a C3.5-alkenyl group, a 2-propen-1-yl group which is substituted by a methoxycarbonyl group, a C3.5-alkynyl group, a phenyl-C1.4-alkyl group wherein the phenyl moiety may be substituted by one or two fluorine atoms, one or two chlorine atoms, a bromine atom, one to three methyl groups, a trifluoromethyl, hydroxy, methoxy, nitro, amino, carboxy or ethoxycarbonyl group, a 2-phenylethyl group wherein the ethyl moiety is substituted in the 2 position by a hydroxy, methoxy or hydroxyimino group, a phenylcarbonylmethyl group wherein the phenyl moiety may be substituted by a fluorine atom or by a methyl, aminocarbonyl, aminosulphonyl, cyano, hydroxy, methoxy, phenoxy, benzyloxy, 2-propen-1-yloxy, 2-propyn-1-yloxy, cyanornethoxy, (methoxycarbonyl)methoxy, (aminocarbonyl)methoxy, (methylaminocarbonyl)-methoxy, (dimethylaminocarbonyl)methoxy, methylsulphonyloxy, phenylsulphonyloxy, nitro, amino, (methoxycarbonyl)methylamino, acetylamino, methoxycarbonylamino, methylsulphonylamino, bis-(methylsulphonyl)-amino, aminocarbonylamino, dimethylaminocarbonylamino, (methylamino)thiocarbonylamino, (ethoxycarbonylamino)carbonylamino or cyanomethylamino group, a phenylcarbonylmethyl group wherein the phenyl moiety is substituted by two methoxy groups or by a bromine atom and by a dimethylamino group, a 2-(phenylcarbonyl)ethyl group, a 2-phenylethenyl group, a 2-(phenoxy) ethyl group, a phenylsulphanylmethyl or phenylsulphinyimethyl group, a naphthylmethyl or naphthylethyl group, an isoxazolylmethyl, thiazolylmethyl, pyridylmethyl, benzo[d]isoxazolylmethyl, benzo[d]isothiazolylmethyl, (1 H-indazol-3-yl)methyl, quinolinylmethyl or iso-quinolinylmethyl group, wherein the heterocyclic moiety may be substituted in each case by a methyl group, an isoquinolinylmethyl group wherein the isoquinolinyl moiety is substituted by a nitro or amino group, a (1,2-dihydro-2-oxo-quinolin-4-yl)methyl group, a pyrrolylethyl, triazolylethyl, thienylethyl, thiazolylethyl or pyridylethyl group, wherein the heterocyclic moiety may be substituted in each case by a methyl group, a thienylcarbonylmethyl group, a methyl group which is substituted by a cyclopropyl, cyano, carboxy, aminocarbonyl or methoxycarbonyl group, an ethyl group which is substituted in the 2 position by a hydroxy, methoxy, dimethylamino, carboxy or methoxycarbonyl group, or a propyl group which is substituted in the 3 position by a hydroxy, dimethylamino, carboxy or methoxycarbonyl group, a 2-oxopropyl group or an amino or benzoylamino group, R2 denotes a hydrogen atom, a C1_6-alkyl group, an ethenyl group, I
a 2-propen-1-yl or 2-propyn-1-yl group, a phenyl group, a phenyl-C,_4-alkyl group wherein the phenyl moiety may be substituted by a fluorine atom, a methyl or methoxy group, a phenylcarbonylmethyl group, a 2-phenylethenyl group, a methyl group which is substituted by a cyclopropyl, cyano, carboxy or methoxy-carbonyl group, or an ethyl group which is substituted in the 2 position by a cyano, hydroxy, methoxy or dimethylamino group, R3 denotes a C4.6-alkenyl group, a 1-cyclopenten-1-ylmethyl or 1-cyclohexen-1-ylmethyl group, a 2-propyn-1-yl, 2-butyn-1-yl or 2-pentyn-1-yl group, a phenyl group which may be substituted by a fluorine atom or a cyano, methyl or trifluoromethyl group, a phenyl group which is substituted by two methyl groups, a benzyl group wherein the phenyl moiety may be substituted by one or two fluorine atoms, an iodine atom or a cyano, nitro or amino group, a furanylmethyl or thienylmethyl group or a cyclopropylmethyl group and R4 denotes a piperidin-1-yl group which is substituted in the 3 position by an amino group, wherein the piperidin-1-yl moiety may additionally be substituted by a methyl group, a 3-amino-piperidin-1-yl group wherein the piperidin-1-yl moiety is additionally substituted by a pyrrolidin-1-yl-carbonyl group, a 3-amino-piperidin-1-yl group wherein the piperidin-1-yl moiety is additionally substituted in the 4 position by a hydroxy group, a 3-amino-piperidin-1-yl group wherein a hydrogen atom in the 2 position together with a hydrogen atom in the 5 position is replaced by a -CH2-CH2-bridge, a hexahydroazepin- 1 -yl group which is substituted in the 3 position by an amino group, a [1,4]diazepan-1-yl group, which is substituted in the 6 position by an amino group, a cyclohexyl group which is substituted in the 3 position by an amino group, a 2-amino-cyclohexylamino group, or an amino group substituted by the groups R15 and R16 wherein R15 denotes a methyl or ethyl group and R16 denotes a 2-aminoethyl group, wherein the ethyl moiety may be substituted by one or two methyl groups or by an aminocarbonyl, methylaminocarbonyl, di methylaminocarbonyl or pyrrolidin-l-ylcarbonyl group, unless otherwise stated, the abovementioned alkyl and alkenyl groups may be straight-chained or branched, the tautomers, enantiomers, diastereomers, mixtures thereof and the salts thereof.
A third sub-group of the particularly preferred compounds of formula I
deserving special mention comprises those compounds of general formula I wherein R', R2 and R3 are as hereinbefore defined and R4 denotes a piperidin-l-yl group which is substituted in the 3 position by an amino group, wherein the piperidin-l-yl moiety may additionally be substituted by a methyl group, a 3-amino-piperidin-1 -yl group wherein the piperidin-i-yl moiety is additionally substituted by a pyrrolidin-l-yl-carbonyl group, a 3-amino-piperidin-l-yl group wherein the piperidin-l-yl moiety in the 4 position is additionally substituted by a hydroxy group, a 3-amino-piperidin-l -yl group wherein a hydrogen atom in the 2 position together with a hydrogen atom in the 5 position is replaced by a -CH2-CH2-bridge, a hexahydroazepin-l-yl group which is substituted in the 3 position by an amino group, a cyclohexyl group which is substituted in the 3 position by an amino group, a 2-amino-cyclohexylamino group, or an amino group substituted by the groups R15 and R16, wherein R15 denotes a methyl or ethyl group and R16 denotes a 2-aminoethyl group, wherein the ethyl moiety may be substituted by one or two methyl groups or by an aminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl or pyrrolidin-i-ylcarbonyl group, unless otherwise stated, the abovementioned alkyl- and alkenyl groups may be straight-chained or branched, the tautomers, enantiomers, diastereomers, mixtures thereof and the salts thereof.
Another sub-group of compounds of general formula I which should be mentioned comprises those compounds wherein R1 denotes a hydrogen atom, a C1.8-alkyl group, a C3_$-alkenyl group, a C3.8-alkynyl group, a C1.6-alkyl group substituted by a group Ra, wherein R. denotes a C3-,-cycloalkyl, heteroaryl, cyano, carboxy, C1.3-alkyloxy-carbonyl, aminocarbonyl, C1.3-alkylamino-carbonyl, di-(C,.3-alkyl)-amino-carbonyl, pyrrolidin-1-ylcarbonyl, piperidin-1-ylcarbonyl, morpholin-4-ylcarbonyl, piperazin-1-ylcarbonyl, 4-methylpiperazin-1 -ylcarbonyl or 4-ethylpiperazin-1-ylcarbonyl group, a C1.6-alkyl group substituted by a phenyl group, wherein the phenyl ring is substituted by the groups R10 to R14 and R10 denotes a hydrogen atom, a fluorine, chlorine, bromine or iodine atom, a C1_4-alkyl, hydroxy, or C1.4-alkyloxy group, a nitro, amino, C1.3-alkylamino, di-(C1.3-alkyl)amino, pyrrolidin-1-yl, piperidin-1-yl, morpholin-4-yl, piperazin-1-yl, 4-(C1.3-alkyl)-piperazin-1-yl, C1.3-alkyl-carbonylamino, arylcarbonylamino, aryl-Cl.3-alkyl-carbonylamino, C1.3-alkyloxy-carbonylamino, aminocarbonylamino, C1.3-alkyl-aminocarbonylamino, di-(C1.3-alkyl)aminocarbonylamino, C1_3-alkyl-sulphonylamino, arylsulphonylamino or aryl-C1.3-alkyl-sulphonylamino group, an N-(C1.3-alkyl)-C1.3-alkyl-carbonylamino, N-(C1.3-alkyl)-arylcarbonylamino, N-(C1.3-alkyl)-aryl-Cl.3-alkyl-carbonylamino, N-(C1.3-alkyl)-C1.3-alkyloxy-carbonylamino, N-(aminocarbonyl)-C,_3-alkylamino, N-(C1.3-alkyl-ami nocarbonyl)-C1.3-alkylamino , N-[di-(C,.3-alkyl)aminocarbonyl]-C1.3-alkylamino, N-(C,.3-alkyl)-Ct.3-alkyl-sulphonylamino, N-(C1-3-alkyl)-aryl-sulphonylamino or N-(C,.3-alkyl)-aryl-C1.3-alkyl-sulphonylamino group, a cyano, carboxy, C1.3-alkyloxy-carbonyl, aminocarbonyl, C1.3-alkyl-aminocarbonyl, di-(C1.3-alkyl)-aminocarbonyl, pyrrolidin-1-yl-carbonyl, piperidin-1-yl-carbonyl, morpholin-4-yl-carbonyl, piperazin-l-yl-carbonyl or 4-(C1_3-alkyl)-piperazin-1-yl-carbonyl group, a C1_3-alkyl-carbonyl or an arylcarbonyl group, a carboxy-C1.3-alkyl, C1.3-alkyloxy-carbonyl-C1.3-alkyl, cyano-C1.3-alkyl, aminocarbonyl-C1.3-alkyl, C1.3-alkyl-aminocarbonyl-C1.3-alkyl, di-(C1.3-alkyl)-aminocarbonyl-C1.3-alkyl, pyrrolidin-1-yl-carbonyl-C1.3-alkyl, piperidin-1-yl-carbonyl-C1.3-alkyl, morpholin-4-yl-carbonyl-C1.3-alkyl, piperazin-1-yl-carbonyl-C1.3-alkyl or 4-(C1.3-al kyl)-piperazin-1-yl-carbonyl-C1.3-alkyl group, a carboxy-C1.3-alkyloxy, C1.3-alkyloxy-carbonyl-Cl.3-alkyloxy, cyano-C1.3-alkyloxy, aminocarbonyl-Cl.3-alkyloxy, C1.3-alkyl-aminocarbonyl-C1.3-alkyloxy, di-(C1.3-alkyl)-aminocarbonyl-C1.3-alkyloxy, pyrrolidin-1-yl-carbonyl-C1.3-alkyl-oxy, piperidin-1-yl-carbonyl-C1.3-alkyloxy, morpholin-4-yl-carbonyl-C1.3-alkyl-oxy, piperazin-1-yl-carbonyl-C1.3-alkyloxy or 4-(C,.3-alkyl)-piperazin-i -yl-carbonyl-C1.3-alkyloxy group, a hydroxy-Cl.3-alkyl, C1.3-alkyloxy-C1.3-alkyl, amino-C1.3-alkyl, C,.3-alkylamino-C,.3-alkyl, di-(C1.3-alkyl)-amino-C1.3-alkyl, pyrrolidin-1-yI-C1.3-alkyl, piperidin-l-yl-C1.3-alkyl, morpholin-4-yl-C1.3-alkyl, piperazin-1-yl-C1.3-alkyl, 4-(C1.3-alkyl)-piperazin-1-yl-C1.3-alkyl group, a hydroxy-C1.3-alkyloxy, C1.3-alkyloxy-C1.3-alkyloxy, amino-C1.3-alkyloxy, C1.3-alkylamino-C1.3-alkyloxy, di-(C1.3-alkyl)-amino-C1.3-alkyloxy, pyrrolidin-l-yI-C1.3-alkyloxy, piperidin-1-yl-C1.3-alkyloxy, morpholin-4-yl-C1.3-alkyloxy, piperazin-1-yI-C1.3-alkyloxy, 4-(C,.3-alkyl)-piperazin-1-yl-C1.3-alkyloxy group, .74-a mercapto, C1.3-alkylsulphanyl, C,_3-alkysulphinyl, C,_3-alkylsulphonyl, C1_3-al kylsulphonyloxy, trifluoromethylsulphanyl, trifluoromethylsulphinyl or trifluoromethylsulphonyl group, a suipho, aminosulphonyl, C,.3-alkyl-aminosulphonyl, di-(C,.3-alkyl)-amino-sulphonyl, pyrrolidin-1-yl-sulphonyl, pipe ridi n- 1 -yl-sul phonyl, morpholin-4-yl-sulphonyl, piperazin-1-yl-sulphonyl or 4-(C1.3-alkyl)-piperazin-1-yl-sulphonyl group, a methyl or methoxy group substituted by 1 to 3 fluorine atoms, an ethyl or ethoxy group substituted by 1 to 5 fluorine atoms, a C2.4-alkenyl or C2.4-alkynyl group, a 2-propen-1-yloxy or 2-propyn-1-yloxy group, a C3_6-cycloalkyl or C3_6-cycloalkyloxy group, a C3.6-cycloalkyl-C1.3-alkyl or C3_6-cycloalkyl-C1_3-alkyloxy group or an aryl, aryloxy, aryl-C1.3-alkyl or aryl-C1.3-alkyloxy group, R" and R12, which may be identical or different, in each case denote a hydrogen atom, a fluorine, chlorine, bromine or iodine atom, a C1.3-alkyl, trifluoromethyl, hydroxy, or C1_3-alkyloxy group or a cyano group, or R11 together with R12, if they are bound to adjacent carbon atoms, also denote a methylenedioxy, difluoromethylenedioxy, straight-chain C3.5-alkylene, -CH=CH-CH=CH, -CH=CH-CH=N or -CH=CH-N=CH group and and R, which may be identical or different, in each case denote a hydrogen atom, a fluorine, chlorine or bromine atom, a trifluoromethyl, C1.3-alkyl or C1.3-alkyloxy group, a phenyl group substituted by the groups R10 to R14, wherein R10 to R14 are as hereinbefore defined, a phenyl-C2.3-alkenyl group wherein the phenyl moiety is substituted by the groups R10 to R14, wherein R10 to R14 are as hereinbefore defined, a phenyl-(CH2)m-A-(CH2)n group wherein the phenyl moiety is substituted by R10 to R14, wherein R10 to R14 are as hereinbefore defined and A denotes a carbonyl, cyanoiminomethylene, hydroxyiminomethylene or C1.3-alkyloxyiminomethylene group, m denotes the number 0, 1 or 2 and n denotes the number 1, 2 or 3, a phenyl-(CH2)m-B-(CH2)ngroup wherein the phenyl moiety is substituted by R10 to R14, wherein R10 to R'4, m and n are as hereinbefore defined and B denotes a methylene group which is substituted by a hydroxy, C1.3-alkyloxy, amino, C,.3-alkylamino, di-(C1.3-alkyl)-amino, mercapto, C1.3-alkylsulphanyl, C1.3-alkylsulphinyl or C1_3-alkylsulphonyl group and is optionally additionally substituted by a methyl or ethyl group, a heteroaryl-(CH2)m-A-(CH2)ngroup, wherein A, m and n are as hereinbefore defined, a heteroaryl-(CH2)m-B-(CH2)ngroup, wherein B, m and n are as hereinbefore defined, a C,_6-alkyl-A-(CH2)õ group, wherein A and n are as hereinbefore defined, a C3_7-cycloalkyl-(CH2)m A-(CH2)n group, wherein A, m and n are as hereinbefore defined, a C3_,-cycloalkyl-(CH2)m-B-(CH2)n group, wherein B, m and n are as hereinbefore defined, a R21-A-(CH2)n group wherein R21 denotes a C,_3-alkyloxycarbonyl, aminocarbonyl, C1.3-alkylaminocarbonyl, di-(C1.3-alkyl)aminocarbonyl, pyrrolidin-1-yl-carbonyl, piperidin-1-yl-carbonyl or morpholin-4-yl-carbonyl, piperazin-1-yi-carbonyl, 4-methylpiperazin-1 -yl-carbonyl or 4-ethylpiperazin-1 -yl-carbonyl group and A
and n are as hereinbefore defined, a phenyl-(CH2)m-D-C1-3-alkyl group wherein the phenyl moiety is substituted by the groups R10 to R14, wherein R10 to R14 and m are as hereinbefore defined and D
denotes an oxygen or sulphur atom, an imino, C1.3-alkylimino, sulphinyl or sulphonyl group, a C2_6-alkyl group substituted by a group Rb, wherein Rb is isolated from the cyclic nitrogen atom in the 1 position of the xanthine skeleton by at least two carbon atoms and Rb denotes a hydroxy, C1.3-alkyloxy, mercapto, C1.3-alkylsulphanyl, C1.3-alkylsulphinyl, C1.3-alkylsulphonyl, amino, C1.3-alkylamino, di-(C1.3-alkyl)-amino, pyrrolidin-1-yl, piperidin-1-yl, morpholin-4-yl, piperazin-1-yl or 4-(C1.3-alkyl)-piperazin-1-yl group, or a C3.6-cycloalkyl group, R2 denotes a hydrogen atom, a C1_8-alkyl group, a C3.6-alkenyl group, a C3.6-alkynyl group, a C1.6-alkyl group substituted by a group Ra, wherein Ra is as hereinbefore defined, a C1.6-alkyl group substituted by a phenyl group, wherein the phenyl ring is substituted by the groups R10 to R'4 and R10 to R14 are as hereinbefore defined, a phenyl group substituted by the groups R10 to R14, wherein R10 to R14 are as hereinbefore defined, a phenyl-C2.3-alkenyl group wherein the phenyl moiety is substituted by the groups R10 to R14, wherein R10 to R14 are as hereinbefore defined, a phenyl-(CH2)m A-(CH2)n group wherein the phenyl moiety is substituted by R10 to R14, wherein R10 to R14, A, m and n are as hereinbefore defined, a phenyl-(CH2)m-B-(CH2)õ group wherein the phenyl moiety is substituted by R10 to R14, wherein R10 to R'4, B, m and n are as hereinbefore defined, a heteroaryl-(CH2)m-A-(CH2)n group, wherein A, m and n are as hereinbefore defined, a heteroaryl-(CH2)m-B-(CH2)n group, wherein B, m and n are as hereinbefore defined, a C1-s-alkyl-A-(CH2)n group, wherein A and n are as hereinbefore defined, a C3.7-cycloalkyl-(CH2)m-A-(CH2)n group, wherein A, m and n are as hereinbefore defined, a C3a-cycloalkyl-(CH2)m B-(CH2)õ group, wherein B, m and n are as hereinbefore defined, a R21-A-(CH2)r, group wherein R21, A and n are as hereinbefore defined, a phenyl-(CH2)m-D-C1.3-alkyl group wherein the phenyl moiety is substituted by the groups R10 to R14, wherein R10 to R14, m and D are as hereinbefore defined, a C2_6-alkyl group substituted by a group Rb, wherein Rb is isolated from the cyclic nitrogen atom in the 3 position of the xanthine skeleton by at least two carbon atoms and is as hereinbefore defined, or a C3.6-cycloalkyl group, R3 denotes a C7_$-alkyl group, a C1.4-alkyl group substituted by the group Rc, wherein R,: denotes a C3_,-cycloalkyl group optionally substituted by one or two C7-3-alkyl groups, a C5-7-cycloalkenyl group optionally substituted by one or two C1.3-alkyl groups or an aryl or heteroaryl group, a C3.8-alkenyl group, a C3.6-alkenyl group substituted by a fluorine, chlorine or bromine atom, or a trifluoromethyl group, a C3.8-alkynyl group, an aryl group or an aryl-C2.4-alkenyl group, and R4 denotes an azetidin-1-yl or pyrrolidin-1-yl group which is substituted in the 3 position by a ReNRd group and may additionally be substituted by one or two C1.3-alkyl groups, wherein Re denotes a hydrogen atom or a C1.3-alkyl group and Rd denotes a hydrogen atom, a C1.3-alkyl group, an Rf-C1-3-alkyl group or a R9 C2.3-alkyl group, wherein Rf denotes a carboxy, C1.3-alkyloxy-carbonyl, aminocarbonyl, C1_3-alkylamino-carbonyl, di-(C1.3-alkyl)-aminocarbonyl, pyrrolidin-1-yl-carbonyl, 2-cyano-pyrrolidin-1-yl-carbonyl, 2-carboxypyrrolidin-1-yl-carbonyl, 2-methoxy-carbonylpyrrolidin-1-yl-carbonyl, 2-ethoxycarbonylpyrrolidin-1-yl-carbonyl, 2-aminocarbonylpyrrolidin-1-yl-carbonyl, 4-cyanothiazolidin-3-yl-carbonyl, 4-carboxythiazolidin-3-yl-carbonyl, 4-methoxycarbonylthiazolidin-3-yl-carbonyl, 4-ethoxycarbonyithiazolidin-3-yl-carbonyl, 4-aminocarbonylthiazolidin-3-yi-carbonyl, pipeadin-1-yl-carbonyl, morpholin-4-yl-carbonyl, piperazin-1-yl-carbonyl, 4-methyl-piperazin-1-yl-carbonyl or 4-ethyl-piperazin-1 -yl-carbonyl group and Rg, which is separated from the nitrogen atom of the ReNRd group by at least two carbon atoms denotes a hydroxy, methoxy or ethoxy group, = _80-a piperidin- 1 -yl or hexahydroazepin-1 -yl group which is substituted in the 3 position or in the 4 position by an ReNRd group and may additionally be substituted by one or two C,.3-alkyl groups, wherein R. and Rd are as hereinbefore defined, a piperidin-1 -yl or hexahydroazepin-1 -yl group substituted in the 3 position by an amino, C1.3-alkylamino or di-(C1.3-alkyl)-amino group, wherein in each case two hydrogen atoms on the carbon skeleton of the piperidin-1-yl or hexahydroazepin-yl group are replaced by a straight-chain alkylene bridge, this bridge containing 2 to carbon atoms if the two hydrogen atoms are located on the same carbon atom, or 1 to 4 carbon atoms, if the hydrogen atoms are located on adjacent carbon atoms, or 1 to 4 carbon atoms, if the hydrogen atoms are located on carbon atoms which are separated by one atom, or 1 to 3 carbon atoms if the two hydrogen atoms are located on carbon atoms separated by two atoms, an azetidin-1-yl, pyrrolidin-1-yl, piperidin-1-yl or hexahydroazepin-1-yl group which is substituted by an amino-C1.3-alkyl, C1_3-alkylamino-C1.3-alkyl or a di-(C1.3-alkyl)amino-C1.3-alkyl group, a piperazin-1 -yl or [1,4]diazepan-1-yl group optionally substituted on the carbon skeleton by one or two C1.3-alkyl groups, a 3-imino-piperazin-1-yl, 3-imino-[1,4]diazepan-1-yl or 5-imino-[1,4]diazepan-1-yl group optionally substituted on the carbon skeleton by one or two C1.3-alkyl groups, a [1,4]diazepan-1-yl group optionally substituted by one or two C1.3-alkyl groups, which is substituted in the 6 position by an amino group, a C3.7-cycloalkyl group which is substituted by an amino, C1.3-alkylamino or di-(C,.3-alkyl)-amino group, a C3_7-cycloalkyl group which is substituted by an amino-C1.3-alkyl, C,_3-alkylamino-C1.3-alkyl or a di-(C1.3-alkyl)amino-Cl.3-alkyl group, a C3.7-cycloalkyl-C1.2-alkyl group wherein the cycloalkyl moiety is substituted by an amino, C1_3-alkylamino or di-(C1.3-alkyl)-amino group, a C3_rcycloalkyl-Cl.2-alkyl group wherein the cycloalkyl moiety is substituted by an amino-C1.3-alkyl, C1.3-alkylamino-C1.3-alkyl or a di-(C1.3-alkyl)amino-C1.3-alkyl group, a C3-7-cycloalkylamino group wherein the cycloalkyl moiety is substituted by an amino, C1.3-alkylamino or di-(C1.3 alkyl)-amino group, wherein the two nitrogen atoms at the cycloalkyl moiety are separated from one another by at least two carbon atoms, a N-(C3.7-cycloalkyl)-N-(C1.3-alkyl)-amino group wherein the cycloalkyl moiety is substituted by an amino, C1.3-alkylamino or di-(C1.3-alkyl)-amino group, wherein the two nitrogen atoms at the cycloalkyl moiety are separated from one another by at least two carbon atoms, a C3.7-cycloalkylamino group wherein the cycloalkyl moiety is substituted by an amino-C1.3-alkyl, C1.3-alkylamino-C1.3-alkyl or a di-(C1.3-alkylamino-C1.3-alkyl group, a N-(C3.7-cycloalkyl)-N-(C1.3-alkyl)-amino group wherein the cycloalkyl moiety is substituted by an amino-C1.3-alkyl, C1.3-alkylamino-C1.3-alkyl or a di-(C1.3-alkyl)amino-C1.3-alkyl group, a C3.7-cycloalkyl-Cl.2-alkyl-amino group wherein the cycloalkyl moiety is substituted by an amino, C1.3-alkylamino or di-(C1.3-alkyl)-amino group, a N-(C3.7-cycloalkyl-Cl.2-alkyl)-N-(C1.ralkyl)-amino group wherein the cycloalkyl moiety is substituted by an amino, C1-alkylamino or di-(C1.3-alkyl)-amino group, a C3.7-cycloalkyl-C1.2-alkyl-amino group wherein the cycloalkyl moiety is substituted by an amino-C1.3-alkyl, C1.3-alkylamino-C1.3-alkyl or a di-(C1.3-alkyl)amino-Cl.3-alkyl group, a N-(C3.7-cycloalkyl-C1 2-alkyl)-N-(C1.2-alkyl)-amino group wherein the cycloalkyl moiety is substituted by an amino-C1-3-alkyl, C1.3-alkylamino-Cl.3-alkyl or a di-(C1_3-alkyl)amino-C1.3-alkyl group, an amino group substituted by the groups R15 and R16 wherein R15 denotes a C1.6-alkyl group, a Cis-cycloalkyl, C3.6-cycloalkyl-C1 3-alkyl, aryl or aryl-C13-alkyl group and R16 denotes a R17-C2.3-alkyl group, wherein the C2_3-alkyl moiety is straight-chained and may be substituted by one to four C1-3-alkyl groups, which may be identical or different, and R17 denotes an amino, C1.3-alkylamino or di-(C1.3-alkyl)-amino group, wherein, if R3 denotes a methyl group, R17 cannot be a di-(C1.3-alkyl)-amino group, an amino group substituted by the group R20, wherein R20 denotes an azetidin-3-yl, azetidin-2-ylmethyl, azetidin-3-ylmethyl, pyrrolidin-3-yl, pyrrolidin-2-ylmethyl, pyrrolidin-3-ylmethyl, piperidin-3-yl, piperidin-4-yi, piperidin-2-ylmethyl, piperidin-3-ylmethyl or piperidin-4-ylmethyl group, wherein the groups mentioned for R20 may each be substituted by one or two C1.3-alkyl groups, an amino group substituted by the groups R15 and R20, wherein R15 and R20 are as hereinbefore defined, wherein the groups mentioned for R20 may each be substituted by one or two C1.3-alkyl groups, a R19-C3.4-alkyl group wherein the C3.4-alkyl moiety is straight-chained and may be substituted by the group R15 and may additionally be substituted by one or two C1_3-alkyl groups, wherein R15 is as hereinbefore defined and R19 denotes an amino, C1.3-alkylamino or di-(C1.3,-alkyl)-amino group, a pyrrolidin-3-yl, piperidin-3-yl, piperidin-4-yl, hexahydroazepin-3-yl or hexahydroazepin-4-yl group, which is substituted in the 1 position by an amino, C1.3-alkylamino or di-(C1.3-alkyl)amino group, or an azetidin-2-yl-C1.2-alkyl, azetidin-3-yl-C1.2-alkyl, pyrrolidin-2-yl-C,_2-alkyl, pyrrolidin-3-yl, pyrrolidin-3-yl-C1.2-alkyl, piperidin-2-yl-C1_2-alkyl, piperidin-3-yl, piperidin-3-yl-C1.2-alkyl, piperidin-4-yl or piperidin-4-yl-C1.2-alkyl group, wherein the abovementioned groups may each be substituted by one or two C1.3-alkyl groups, wherein by the aryl groups mentioned in the definition of the abovementioned groups are meant phenyl groups which may be mono- or disubstituted independently of one another by Rh, wherein the substituents may be identical or different and Rh denotes a fluorine, chlorine, bromine or iodine atom, a trifluoromethyl, C1.3-alkyl, cyclopropyl, ethenyl, ethynyl, hydroxy, C1.3-alkyloxy, difluoromethoxy or trifluoromethoxy group, by the heteroaryl groups mentioned in the definition of the abovementioned groups are meant a pyrrolyl, furanyl, thienyl, pyridyl, indolyl, benzofuranyl, benzothiophenyl, quinolinyl or isoquinolinyl group, or a pyrrolyl, furanyl, thienyl or pyridyl group wherein one or two methyne groups are replaced by nitrogen atoms, or an indolyl, benzofuranyl, benzothiophenyl, quinolinyl or isoquinolinyl group wherein one to three methyne groups are replaced by nitrogen atoms, wherein the five-membered groups or parts of molecules may in each case be substituted by a C1.3-alkyl or trifluoromethyl group and the six-membered groups or parts of molecules may each be substituted by one or two C,_3-alkyl groups or by a fluorine, chlorine, bromine or iodine atom, by a trifluoromethyl, hydroxy, C,_3-alkyloxy, difluoromethoxy or trifluoromethoxy group, while unless otherwise stated the abovementioned alkyl, alkenyl and alkynyl groups may be straight-chained or branched, as well as the derivatives which are N-oxidised or methylated or ethylated at the cyclic nitrogen atom in the 9 position of the xanthine skeleton, with the proviso that the compounds wherein R' denotes a hydrogen atom, a methyl, propyl, 2-hydroxypropyl, aminocarbonyl-methyl or benzyl group, R2 denotes a methyl group, R3 denotes a C,_$-alkyl group, a benzyl group optionally substituted by a fluorine, chlorine or bromine atom or a methyl group, a 1 -phenylethyl or 2-phenylethyl group, a 2-propen-1-yl, 2-buten-1-yl, 3-chloro-2-buten-1-yl or 2-methyl-2-propen-1 -yl group and R4 denotes a piperazin-1-yl group, are excluded, and with the proviso that the compounds wherein R1 denotes a hydrogen atom or a methyl group, R2 denotes a hydrogen atom or a methyl group, R3 denotes a methyl group and R4 denotes a 3-aminopropyl, 3-[di-(C1_3-alkyl)amino]-propyl, 1-phenyl-3-[di-(C,_3-alkyl)amino]-propyl, 1-phenyl-3-methyl-3-(dimethylami no)-propyl, 1-(4-chlorophenyl)-3-(dimethylamino)-propyl, 1-phenyl-2-methyl-3-(dimethylamino)-propyl, 1-(3-methoxyphenyl)-3-(dimethylamino)-propyl or a 4-aminobutyl group, are excluded, and with the proviso that the compound 1,3,7-timethyl-8-(1-aminocyclohexyl)-xanthine is excluded, the isomers and the salts thereof.
I

The following preferred compounds are mentioned by way of example:
(1) 1,3-dimethyl-7-benzyl-8-(3-amino-pyrrolidin-1-yl)-xanthine, (2) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-pyrrolidin-1-yl)-xanthine, (3) 1,3-dimethyl-7-benzyl-8-(3-amino-piperidin-1-yl)-xanthine, (4) 1,3-dimethyl-7-(3-methyl-2-buten-1-yi)-8-[(trans-2-amino-cyclohexyl)amino]-xanthine, (5) 1,3-dimethyl-7-(3-methyl-2-buten-1 -yi)-8-(3-amino-piperidin-1 -yl)-xanthine, (6) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-(4-amino-piperidin-1-yl)-xanthine, (7) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-[(cis-2-amino-cyclohexyl)amino]-xanthine, (8) 1,3-dimethyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine, (9) 1,3-dimethyl-7-[(1-cyclopenten-1-yl)methyl]-8-(3-amino-piperidin-1-yl)-xanthine, (10) 1,3-dimethyl-7-(2-thienylmethyl)-8-(3-amino-piperidin-1-yl)-xanthine, (11) 1,3-dimethyl-7-(3-fluorobenzyl)-8-(3-amino-piperidin-1-yl)-xanthine, (12) 1,3-dimethyl-7-(2-fluorobenzyl)-8-(3-amino-piperidin-1-yl)-xanthine, (13) 1,3-dimethyl-7-(4-fluorobenzyl)-8-(3-amino-piperidin-1-yl)-xanthine, (14) 1,3-dimethyl-7-(2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine, (15) 1,3-bis-(cyclopropylmethyl)-7-benzyl-8-(3-amino-piperidin-1-yl)-xanthine, (16) (R)-1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine, (17) (S)-1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yi)-xanthine, (18) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-hexahydroazepin-l -yl)-xanthine, (19) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-(4-amino-hexahydroazepin-l -yl)-xanthine, (20) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-(cis-3-amino-cyclohexyl)-xanthine-hydrochloride, (21) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-(3-methylamino-piperidin-1-yl)-xanthine, (22) 1-(2-phenylethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine, (23) 1,3-dimethyl-7-(3-methyl-2-buten-1-yi)-8-[N-(2-aminoethyl)-methylamino]-xanthine, (24) 1-[2-(thiophen-2-yl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine, (25) 1-[2-(thiophen-3-yl)-ethyl]-3-methyl-7-(3-methyl-2-buten- l -yl)-8-(3-ami no-piperidin-1-yl)-xanthine, (26) 1-[2-(2-methyl-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine, (27) 1-[2-(3-methyl-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine, (28) 1-[2-(3-methoxy-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1 -yl)-8-(3-amino-piperidin-1-yl)-xanthine, (29) 1-((E)-2-phenyl-vinyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-l -yl)-xanthine, (30) 1-(2-phenyl-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine, (31) 1-(2-phenyl-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine, (32) 1-[2-(2-methoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine, (33) 1-[2-(thiophen-3-yl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine, (34) 1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine, (35) 1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine, 36) 1-[(isoquinolin-1-yl)methyl]-3-methyl-7-(3-methyl-2-buten-l -yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine, (37) 1-[(isoquinolin-1-yl)methyl]-3-methyl-7-(3-methyl-2-buten-l-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine and (38) 1-[(1-naphthyl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine and the salts thereof.

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

a) In order to prepare compounds of general formula I wherein R4 is one of the abovementioned groups linked to the xanthine skeleton via a nitrogen atom:

reacting a compound of general formula R N
N
>-Zl ( Ill ), I

I wherein R' to R3 are as hereinbefore defined and Z' denotes a leaving group such as a halogen atom, a substituted hydroxy, mercapto, sulphinyl, sulphonyl or sulphonyloxy group such as a chlorine or bromine atom, a methanesulphonyl or methanesulphonyloxy group, with a compound of general formula H - R4, (IV), wherein R4, denotes one of the groups mentioned for R4 hereinbefore, which is linked to the xanthine skeleton of general formula I via a nitrogen atom.

The reaction is expediently carried out in a solvent such as isopropanol, butanol, tetrahydrofuran, dioxan, toluene, chlorobenzene, di methylformamide, dimethyl-sulphoxide, methylene chloride, ethylene glycol monomethylether, ethylene glycol diethylether or sulpholane optionally in the presence of an inorganic or tertiary organic base, e.g. sodium carbonate or potassium hydroxide, a tertiary organic base, e.g. triethylamine, or in the presence of N-ethyl-diisopropylamine (Hunig base), while these organic bases may simultaneously serve as solvent, and optionally in the presence of a reaction accelerator such as an alkali metal halide or a palladium-based catalyst at temperatures between -20 and 180 C, preferably however at temperatures between -10 and 120 C. The reaction may however also be carried out without a solvent or in an excess of the compound of general formula IV used.

b) In order to prepare a compound of general formula I wherein R4 according to the definition given earlier contains an amino group or an alkylamino group optionally substituted in the alkyl moiety:

deprotecting a compound of general formula R\N N
/>-R4.. (V), I

wherein R1, R2 and R3 are as hereinbefore defined and R4.. contains an N-tert.-butyloxycarbonylamino group or an N-tert.-butyloxycarbonyl-N-alkylamino group, wherein the alkyl moiety of the N-tert.-butyloxycarbonyl-N-alkyl-amino group may be substituted as mentioned hereinbefore.

The tert.-butyloxycarbonyl group is preferably cleaved by treating with an acid such as trifluoroacetic acid or hydrochloric acid or by treating with bromotrimethylsilane or iodotrimethylsilane, optionally using a solvent such as methylene chloride, ethyl acetate, dioxan, methanol or diethyl ether at temperatures between 0 and 80 C.

c) In order to prepare a compound of general formula I wherein R2 as hereinbefore defined denotes a hydrogen atom:

deprotecting a compound of general formula RAN N
O i N

R2 (VI), wherein R', R3 and R4 are as hereinbefore defined and Rz denotes a protecting group such as a methoxymethyl, benzyloxymethyl, methoxyethoxymethyl or 2-(trimethylsilyl)ethyloxymethyl group.

The protecting group is cleaved, for example, using an acid such as acetic acid, trifluoroacetic acid, hydrochloric acid, sulphuric acid or an acid ion exchanger in a solvent such as methylene chloride, tetrahydrofuran, methanol, ethanol or isopropanol or mixtures thereof, while the 2-(trimethylsilyl)ethyloxymethyl group may also be cleaved using hydrofluoric acid or a salt of hydrofluoric acid such as tetrabutylammonium fluoride.

If according to the invention a compound of general formula I is obtained which contains an amino, alkylamino or imino group, this may be converted by acylation or sulphonylation into a corresponding acyl or sulphonyl compound of general formula if a compound of general formula I is obtained which contains an amino, alkylamino or imino group, this may be converted by alkylation or reductive alkylation into a corresponding alkyl compound of general formula I;

if a compound of general formula I is obtained which contains a nitro group, this may be converted by reduction into a corresponding amino compound;

if a compound of general formula I is obtained which contains an imino group, this may be converted by nitrosation and subsequent reduction into a corresponding N-amino-imino compound;

if a compound of general formula I is obtained which contains a C,_3-alkyloxy-carbonyl group, this may be converted by cleavage of the ester into the corresponding carboxy compound;

if a compound of general formula I is obtained wherein R' contains a carbonyl group, this may be converted by reaction with hydroxylamine into a corresponding oxime of general formula I;

if a compound of general formula I is obtained which contains a carboxy group, this may be converted by esterification into a corresponding ester of general formula I; or if a compound of general formula I is obtained which contains a carboxy or ester group, this may be converted by reaction with an amine into a corresponding amide of general formula I.

The subsequent esterification is optionally carried out in a solvent or mixture of solvents such as methylene chloride, dimethylformamide, benzene, toluene, chlorobenzene, tetrahydrofuran, benzene/tetrahydrofuran or dioxan or particularly advantageously in a corresponding alcohol optionally in the presence of an acid such as hydrochloric acid or in the presence of a dehydrating agent, e.g. in the presence of isobutyl chloroformate, thionyl chloride, trimethylchiorosilane, sulphuric acid, methanesuIphonic acid, p-toluenesulphonic acid, phosphorus trichloride, phosphorus pentoxide, N,N'-dicyclohexylcarbodiimide, N,N'-dicyclohexylcarbodiimide/N-hydroxysuccinimide or 1-hydroxy-benzotriazole and optionally additionally in the presence of 4-dimethylamino-pyridine, N,N'-carbonyldiimidazole or triphenyiphosphine/carbon tetrachloride, conveniently at temperatures between 0 and 150 C, preferably at temperatures between 0 and 80 C.

The subsequent ester formation may also be carried out by reacting a compound which contains a carboxy group with a corresponding alkyl halide.

The subsequent acylation or sulphonylation is optionally carried out in a solvent or mixture of solvents such as methylene chloride, dimethylformamide, benzene, toluene, chlorobenzene, tetrahydrofuran, benzene/tetrahydrofuran or dioxan with a corresponding acyl or sulphony derivative optionally in the presence of a tertiary organic base or in the presence of an inorganic base or in the presence of a dehydrating agent, e.g. in the presence of isobutyl chloroformate, thionyl chloride, trimethylchlorosilane, sulphuric acid, methanesu I phonic acid, p-tol uenesu I
phonic acid, phosphorus trichloride, phosphorus pentoxide, N,N'-dicyclohexylcarbodiimide, N,N'-dicyclohexylcarbodiimide/N-hydroxysuccinimide or 1-hydroxy-benzotriazole and optionally additionally in the presence of 4-dimethylamino-pyridine, N,N'-carbonyldiimidazole or triphenylphosphine/carbon tetrachloride, conveniently at temperatures between 0 and 150 C, preferably at temperatures between 0 and 80 C.

The subsequent alkylation is optionally carried out in a solvent or mixture of solvents such as methylene chloride, dimethylformamide, benzene, toluene, chlorobenzene, tetrahydrofuran, benzene/tetrahydrofuran or dioxan with an alkylating agent such as a corresponding halide or sulphonic acid ester, e.g. with methyl iodide, ethyl bromide, dimethylsulphate or benzyl chloride, optionally in the presence of a tertiary e7 organic base or in the presence of an inorganic base conveniently at temperatures between 0 and 150 C, preferably at temperatures between 0 and 100 C.

The subsequent reductive alkylation is carried out with a corresponding carbonyl compound such as formaldehyde, acetaldehyde, propionaldehyde, acetone or butyraldehyde in the presence of a complex metal hydride such as sodium borohydride, lithium borohydride, sodium triacetoxyborohydride or sodium cyanoborohydride conveniently at a pH of 6-7 and at ambient temperature or in the presence of a hydrogenation catalyst, e.g. with hydrogen in the presence of palladium/charcoal, at a hydrogen pressure of 1 to 5 bar. The methylation may also be carried out in the presence of formic acid as reducing agent at elevated temperature, e.g. at temperatures between 60 and 120 C.

The subsequent reduction of a nitro group is carried out for example with hydrogen and a catalyst such as palladium on activated charcoal, platinum dioxide or Raney nickel, or using other reducing agents such as iron or zinc in the presence of an acid such as acetic acid.

Subsequent nitrosation of an imino group followed by reduction to obtain the N-amino-imino compound is carried out for example so that the imino compound is nitrosated with an alkyl nitrite such as isoamyl nitrite and the N-nitroso-imino 1 compound formed is then reduced directly to form the N-amino-imino compound;
zinc, for example, in the presence of an acid such as acetic acid is suitable for this purpose.

The subsequent cleaving of a C,_3-alkyloxycarbonyl group to obtain the carboxy group is carried out, for example, by hydrolysis with an acid such as hydrochloric acid or sulphuric acid or an alkali metal hydroxide such as lithium hydroxide, sodium hydroxide or potassium hydroxide.

The subsequent amide formation is carried out by reacting a corresponding reactive carboxylic acid derivative with a corresponding amine optionally in a solvent or mixture of solvents such as methylene chloride, dimethylformamide, benzene, toluene, chlorobenzene, tetrahydrofuran, benzene/tetrahydrofu ran or dioxan, while the amine used may simultaneously serve as solvent, optionally in the presence of a tertiary organic base or in the presence of an inorganic base or with a corresponding carboxylic acid in the presence of a dehydrating agent, e.g. in the presence of isobutyl chloroformate, thionyl chloride, trimethylchlorosilane, phosphorus trichloride, phosphorus pentoxide, N,N'-dicyclohexylcarbodiimide, N,N'-dicyclohexylcarbodiimide/N-hydroxysuccinimide or 1-hydroxy-benzotriazole and optionally additionally in the presence of 4-dimethylamino-pyridine, N,N'-carbonyldiimidazole or triphenylphosphine/carbon tetrachloride, conveniently at temperatures between 0 and 150 C, preferably at temperatures between 0 and 80 C.

In the reactions described hereinbefore, any reactive groups present such as hydroxy, carboxy, amino, alkylamino or imino groups may be protected during the reaction by conventional protecting groups which are cleaved again after the reaction.

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

Any protecting group used is optionally subsequently cleaved for example by hydrolysis in an aqueous solvent, e.g. in water, isopropanol/water, acetic acid/water, tetrahydrofuran/water or dioxan/water, in the presence of an acid such as trifluoroacetic acid, hydrochloric acid or sulphuric acid or in the presence of an alkali metal base such as sodium hydroxide or potassium hydroxide or aprotically, e.g. in the presence of iodotrimethylsilane, at temperatures between 0 and 120 C, preferably at temperatures between 10 and 100 C.

However, a benzyl, methoxybenzyl or benzyloxycarbonyl group is cleaved, for example, hydrogenolytically, e.g. with hydrogen in the presence of a catalyst such as palladium/charcoal in a suitable solvent such as methanol, ethanol, ethyl acetate or glacial acetic acid optionally with the addition of an acid such as hydrochloric acid at temperatures between 0 and 100 C, but preferably at ambient temperatures between 20 and 60 C, and at a hydrogen pressure of 1 to 7 bar, but preferably from _96-3 to 5 bar. However, a 2,4-dimethoxybenzyl group is preferably cleaved in trifluoroacetic acid in the presence of anisole.

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

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

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

Moreover, the compounds of general formula I obtained may be resolved into their enantiomers and/or diastereomers, as mentioned hereinbefore. Thus, for example, cis/trans mixtures may be resolved into their cis and trans isomers, and compounds with at least one optically active carbon atom may be separated into their enantiomers.
Thus, for example, the cis/trans mixtures may be resolved by chromatography into the cis and trans isomers thereof, the compounds of general formula I obtained which occur as racemates may be separated by methods known per se (cf.
Allinger N. L. and Eliel E. L. in "Topics in Stereochemistry", Vol. 6, Wiley Interscience, 1971) into their optical antipodes and compounds of general formula I with at least asymmetric carbon atoms may be resolved into their diastereomers on the basis of their physical-chemical differences using methods known per se, e.g. by chromatography and/or fractional crystallisation, and, if these compounds are obtained in racemic form, they may subsequently be resolved into the enantiomers as mentioned above.

The enantiomers are preferably separated by column separation on chiral phases or by recrystallisation from an optically active solvent or by reacting with an optically active substance which forms salts or derivatives such as e.g. esters or amides with the racemic compound, particularly acids and the activated derivatives or alcohols thereof, and separating the diastereomeric mixture of salts or derivatives thus obtained, e.g. on the basis of their differences in solubility, whilst the free antipodes may be released from the pure diastereomeric salts or derivatives by the action of suitable agents. Optically active acids in common use are e.g. the D- and L-forms of tartaric acid or dibenzoyltartaric acid, di-o-tolyltartaric acid, malic acid, mandelic acid, camphorsulphonic acid, glutamic acid, aspartic acid or quinic acid. An optically active alcohol may be for example (+) or (-)-menthol and an optically active acyl group in amides, for example, may be a (+)-or (-)-menthyloxycarbonyl.

Furthermore, the compounds of formula I may be converted into the salts thereof, particularly for pharmaceutical use into the physiologically acceptable salts with inorganic or organic acids. Acids which may be used for this purpose include for example hydrochloric acid, hydrobromic acid, sulphuric acid, methanesulphonic acid, phosphoric acid, fumaric acid, succinic acid, lactic acid, citric acid, tartaric acid or maleic acid.

Moreover, if the new compounds of formula I thus obtained contain a carboxy group, they may subsequently, if desired, be converted into the salts thereof with inorganic or organic bases, particularly for pharmaceutical use into the physiologically acceptable salts thereof. Suitable bases for this purpose include for example sodium hydroxide, potassium hydroxide, arginine, cyclohexylamine, ethanolamine, diethanolamine and triethanolamine.

The compounds of general formulae III to VI used as starting materials are either known from the literature or may be obtained by methods known from the literature (cf. Examples Ito XXXI).

For example, a starting compound of general formula III may be obtained by reacting a theophylline derivative halogenated in the 8 position with a correspondingly substituted alkyl halide.

As already mentioned hereinbefore, the compounds of general formula I
according to the invention and the physiologically acceptable salts thereof have valuable pharmacological properties, particularly an inhibiting effect on the enzyme DPP-IV.
The biological properties of the new compounds were investigated as follows:

The ability of the substances and their corresponding salts to inhibit the DPP-IV
activity can be demonstrated in an experiment in which an extract of the human colon carcinoma cell line Caco-2 is used as the DPP IV source. This cell line was obtained from the American Type Culture Collection (ATCC HTB 37). The differentiation of the cells in order to induce the DPP-IV expression was carried out in accordance with the description by Reiher et al. in an article entitled "Increased expression of intestinal cell line Caco-2" , which appeared in Proc. Natl.
Acad. Sci.
Vol. 90, pp. 5757-5761 (1993). The cell extract was obtained from cells solubilised in a buffer (10mM Tris HCI, 0.15 M NaCl, 0.04 t.i.u. aprotinin, 0.5% Nonidet-P40, pH
8.0) by centrifugation at 35,000 g for 30 minutes at 4 C (to remove cell debris).

The DPP-IV assay was carried out as follows:

50 NI of substrate solution (AFC; AFC is amido-4-trifluoromethylcoumarin), final concentration 100 iuM, were placed in black microtitre plates. 20 N1 of assay buffer (final concentrations 50 mM Tris HCI pH 7.8, 50 mM NaCl, 1 % DMSO) was pipetted in. The reaction was started by the addition of 30 Sul of solubilised Caco-2 protein (final concentration 0.14,ug of protein per well). The test substances under investigation were typically added prediluted to 20 NI, while the volume of assay buffer was then reduced accordingly. The reaction was carried out at ambient temperature, the incubation period was 60 minutes. Then the fluorescence was measured in a Victor 1420 Multilabel Counter, with the excitation wavelength at 405 nm and the emission wavelength at 535 nm. Dummy values (corresponding to 0 %
activity) were obtained in mixtures with no Caco-2 protein (volume replaced by assay buffer), control values (corresponding to 100 % activity) were obtained in mixtures without any added substance. The potency of the test substances in question, expressed as IC5o values, were calculated from dosage/activity curves consisting of 11 measured points in each case. The following results were obtained:
Compound DPP IV inhibition (Example No.) IC50 [nM]
1 (2) 82 1(6) 230 1(15) 624 1(16) 78 1(19) 2770 1(21) 124 1(25) 56 1(27) 125 1(28) 166 1(30) 2050 1(34) 205 1(35) 95 1(55) 142 1(60) 57 1(62) 167 1(70) 32 1(97) 212 1(121) 10 2(1) 22 2(22) 66 2(28) 5 2(56) 64 2(77) 22 2(85) 17 2(88) 6 2(113) 20 2(119) 2 2(127) 22 2(131) 127 2(136) 3 The compounds prepared according to the invention are well tolerated as no toxic side effects could be detected in rats after the oral administration of 30 mg/kg of the compound of Example 1(2), for example.

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 influencing any conditions or diseases which can be affected by the inhibition of the DPP-IV activity. It is therefore to be expected that the compounds according to the invention will be suitable for the prevention or treatment of diseases or conditions such as type I and type 11 diabetes mellitus, diabetic complications, metabolic acidosis or ketosis, insulin resistance, dyslipidaemias of various origins, arthritis, atherosclerosis and related diseases, obesity, allograft transplantation and osteoporosis caused by calcitonin. In addition, these substances are suitable for preventing B-cell degeneration such as e.g. apoptosis or necrosis of pancreatic B-cells. The substances are also suitable for improving or restoring the function of pancreatic cells and additionally increasing the size and number of pancreatic B-cells. Additionally, on the basis of the role of the glucagon-like peptides such as e.g. GLP-1 and GLP-2 and their link with DPP-IV inhibition, it is expected that the compounds according to the invention will be suitable for achieving, inter alia, a sedative or tranquillising effect, as well as having a favourable effect on catabolic states after operations or hormonal stress responses or possibly reducing mortality and morbidity after myocardial infarct. Moreover, they are suitable for treating any conditions connected with the effects mentioned above and mediated by GLP-1 or GLP-2. The compounds according to the invention may also be used as diuretics or anti hypertensives and are suitable for preventing and treating acute kidney failure. They are also suitable for preventing and treating chronic inflammatory bowel diseases. It is also expected that DPP-IV inhibitors and hence the compounds according to the invention can be used to treat infertility or to improve fertility in humans or mammals, particularly if the infertility is connected with insulin resistance or with polycystic ovary syndrome. In addition, the substances are T suitable for treating growth hormone deficiencies connected with restricted growth.
The compounds according to the invention may also be used in conjunction with other active substances. Suitable therapeutic agents for such combinations include for example antidiabetic agents such metformin, suiphonylureas (e.g.
glibenclamid, tolbutamide, glimepiride), nateglinide, repaglinide, thiazolidinediones (e.g.
rosiglitazone, pioglitazone), PPAR-gamma-agonists (e.g. GI 262570), alpha-glucosidase inhibitors (e.g. acarbose, voglibose), alpha2-antagonists, insulin and insulin analogues, GLP-1 and GLP-1 analogues (e.g. exendin-4) or amylin. The list also includes inhibitors of protein tyrosinephosphatase 1, substances that affect deregulated glucose production in the liver, such as e.g. inhibitors of glucose-6-phosphatase, or fructose-1,6-bisphosphatase, glycogen phosphorylase, glucagon receptor antagonists and inhibitors of phosphoenol pyruvate carboxykinase, glycogen synthase kinase or pyruvate dehydrokinase, lipid lowering agents such as for example HMG-CoA-reductase inhibitors (e.g. simvastatin, atorvastatin), fibrates (e.g. bezafibrat, fenofibrat), nicotinic acid and the derivatives thereof, cholesterol absorption inhibitors such as, for example, ezetimibe, bile acid-binding substances such as, for example, cholestyramine, HDL-increasing compounds such as CETP
inhibitors or ABC1 regulators or active substances for treating obesity, such as sibutramin or tetrahydrolipstatin or 133-agonists such as SB-418790 or AD-9677.

Moreover, combinations with drugs for influencing high blood pressure such as e.g.
All antagonists or ACE inhibitors, diuretics, B-blockers and others or combinations thereof are suitable.

The dosage required to achieve such an effect is appropriately 1 to 100 mg, preferably 1 to 30 mg, by intravenous route, and 1 to 1000 mg, preferably 1 to mg, by oral route, in each case administered 1 to 4 times a day. For this purpose, the compounds of formula I prepared according to the invention may be formulated, optionally together with other active substances, together with one or more inert conventional carriers and/or diluents, e.g. with corn starch, lactose, glucose, microcrystalline cellulose, magnesium stearate, polyvinylpyrrolidone, citric acid, tartaric acid, water, water/ethanol, water/glycerol, water/sorbitol, water/polyethylene glycol, propylene glycol, cetylstearyl alcohol, carboxy methylcel I u lose or fatty substances such as hard fat or suitable mixtures thereof, to produce conventional galenic preparations such as plain or coated tablets, capsules, powders, suspensions or suppositories.

The Examples which follow are intended to illustrate the invention I

Preparation of the starting compounds:

Example I
1 3-dimethyl-7-benzyl-8-chloro-xanthine A mixture of 20 g of 8-chlorotheophylline, 150 ml of dimethylformamide, 10.2 ml of benzyl bromide and 15.5 ml of N-ethyl-diisopropylamine is stirred overnight at ambient temperature. The reaction mixture is poured onto 600 ml of water. The solid is suction filtered, washed with water and diethylether and dried.
Yield: 14.6 g (51 % of theory) Melting point: 155 C
Rf value: 0.84 (silica gel, ethyl acetate/methanol = 9:1) The following compounds are obtained analogously to Example I:
(1) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-chloro-xanthine Melting point: 104 C
Mass spectrum (El): m/z = 282, 284 [M]+

(2) 1,3-dimethyl-7-(2-butyn-1-yl)-8-chloro-xanthine Melting point: 105-108 C
Rf value: 0.55 (silica gel, methylene chloride/methanol = 20:1) (3) 1,3-dimethyl-7-[(1-cyclopenten-1-yl)methyl]-8-chloro-xanthine Rf value: 0.50 (silica gel, methylene chloride/methanol = 20:1) (4) 1,3-dimethyl-7-(2-thienylmethyl)-8-chloro-xanthine Rf value: 0.35 (silica gel, methylene chloride/methanol = 50:1) Mass spectrum (El): m/z = 310, 312 [M]+

(5) 1,3-dimethyl-7-(3-fluorobenzyl)-8-chloro-xanthine Rf value: 0.60 (silica gel, methylene chloride/methanol = 20:1) (6) 1,3-dimethyl-7-(2-fluorobenzyl)-8-chloro-xanthine Mass spectrum (El): m/z = 322, 324 [M]+

(7)1,3 -dimethyl-7-(3-methyl-2-buten-1 -yl)-8-(cis-3-tert.-butyloxycarbonylamino-cyclohexyl)-xanthine Mass spectrum (ESI+): m/z = 446 [M+H]+

(8) 1,3-dimethyl-7-(4-fluorobenzyl)-8-chloro-xanthine Rf value: 0.60 (silica gel, methylene chloride/methanol = 20:1) (9) 1,3-dimethyl-7-(2-buten-1-yl)-8-chloro-xanthine Rf value: 0.70 (silica gel, methylene chloride/methanol = 10:1) (10) 3-methyl-7-(3-methyl-2-buten-1-yl)-8-chloro-xanthine Melting point: 226-228 C
Rf value: 0.66 (silica gel, methylene chloride/methanol = 9:1) Mass spectrum (ESI+): m/z = 269, 271 [M+H]+

(11) 3-methyl-7-(3-methyl-2-buten-1-yi)-8-bromo-xanthine Mass spectrum (ESI+): n'z = 313, 315 [M+H]+
Rt value: 0.48 (silica gel, methylene chloride/methanol = 10:1) (12) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)propyl]-xanthine Mass spectrum (ESI+): m/z = 406 [M+H]+

(13) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-[1-(tert.-butyloxycarbonyl)-piperidin-4-yl]-xanthine Carried out in the presence of potassium carbonate in dimethylformamide at 60 C.
Mass spectrum (ESI+): m/z = 432 [M+H]+

(14) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-[trans-2-(tert.-butyloxycarbonylamino)-cyclohexyl]-xanthine Mass spectrum (ESI+): m/z = 446 [M+H]+

(15) 1,3-dimethyl-7-(2-pentyn-1-yl)-8-chloro-xanthine Mass spectrum (ESI+): m/z = 281, 283 [M+H]+

(16) 3-methyl-7-benzyl-8-chloro-xanthine Mass spectrum (ESI+): m/z = 291, 293 [M+H]+

(17) 3-methyl-7-cyclopropylmethyl-8-chloro-xanthine Mass spectrum (El): m/z = 254, 256 [M]+

(18) 3-methyl-7-(2-butyn-1-yl)-8-chloro-xanthine Mass spectrum (ESI+): rrt/z = 253, 255 [M+H]+

(19) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-bromo-xanthine Mass spectrum (ESI+): m/z = 327, 329 [M+H]+

(20) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-cyclohexyl]-xanthine (cis/trans mixture) Mass spectrum (ESI+): rn/z = 446 [M+H]+

(21) 1,3-dimethyl-7-[(thiophen-3-yl)-methyl]-8-chloro-xanthine Rf value: 0.42 (silica gel, cyclohexane/ethyl acetate = 1:1) (22) 1,3-dimethyl-7-[(thiophen-2-yl)-methyl]-8-chloro-xanthine 1H-NMR (300 MHz, CDCI3): characteristic signals at 3.40 and 3.52 ppm (in each case s, in each case 3H), 5.70 ppm (s, 2H), 6.95 ppm (m, 1 H) and 7.25 ppm (m, 2H) (23) 1,3-dimethyl-7-[(furan-3-yl)-methyl]-8-chloro-xanthine Rf value: 0.44 (silica gel, ethyl acetate/hexane = 1:1) (24) 1,3-dimethyl-7-[(furan-2-yl)-methyl]-8-chloro-xanthine Rf value: 0.50 (silica gel, ethyl acetate/hexane = 1:1) (25) 1,3-dimethyl-7-(2-propyn-1-yl)-8-chloro-xanthine Rf value: 0.33 (silica gel, ethyl acetate/hexane = 1:1) (26) 1,3-dimethyl-7-(2,3-dimethyl-2-buten-1-yl)-8-chloro-xanthine Rf value: 0.51 (silica gel, ethyl acetate/hexane = 1:1) (27) 1,3-dimethyl-7-((E)-2-methyl-2-buten-1-yl)-8-chloro-xanthine Rf value: 0.57 (silica gel, ethyl acetate/hexane = 1:1) (28) 1,3-dimethyl-7-[(cyclohexen-1-yl)-methyl]-8-chloro-xanthine Rf value: 0.62 (silica gel, ethyl acetate/hexane = 1:1) (29) 1,3-dimethyl-7-[(cyclopenten-1-yl)-methyl]-8-chloro-xanthine Rf value: 0.54 (silica gel, ethyl acetate/hexane = 1:1) (30) 1,3-dimethyl-7-((Z)-2-methyl-2-buten-1-yl)-8-(piperazin-l-yl)-xanthine Rf value: 0.51 (silica gel, ethyl acetate = 1:1) (31) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-[1-(tert.-butyloxycarbonyl)-piperidin-3-yl]-xanthine Carried out in the presence of potassium carbonate Mass spectrum (ESI+): m/z = 432 [M+H]+

(32) 1,3-dimethyl-7-[(2-naphthyl)methyl]-8-chloro-xanthine Carried out in the presence of potassium carbonate Rf value: 0.60 (silica gel, cyclohexane/ethyl acetate = 1:1) Mass spectrum (ESI+): m/z =377, 379 [M+Na]+

(33) 1,3-dimethyl-7-[(1-naphthyl)methyl]-8-chloro-xanthine Carried out in the presence of potassium carbonate Rf value: 0.60 (silica gel, cyclohexane/ethyl acetate = 1:1) Mass spectrum (ESI+): m/z = 355, 357 [M+H]+

(34) 1,3-dimethyl-7-(2-cyano-benzyl)-8-chloro-xanthine Carried out in the presence of potassium carbonate Rf value: 0.60 (silica gel, cyclohexane/ethyl acetate = 1:1) Mass spectrum (ESI+): m/z = 330, 332 [M+H]+

(35) 1,3-dimethyl-7-(3-cyano-benzyl).-8-chloro-xanthine Carried out in the presence of potassium carbonate Rf value: 0.60 (silica gel, cyclohexane/ethyl acetate = 1:1) Mass spectrum (ESI+): m/z = 330, 332 [M+H]+

(36) 1,3-dimethyl-7-(3,5-difluoro-benzyl)-8-chloro-xanthine Carried out in the presence of potassium carbonate Rf value: 0.60 (silica gel, cyclohexane/ethyl acetate = 1:1) Mass spectrum (El): m/z = 340, 342 [M]+

(37) 1,3-dimethyl-7-(4-cyano-benzyl)-8-chloro-xanthine Carried out in the presence of potassium carbonate Rf value: 0.60 (silica gel, cyclohexane/ethyl acetate = 1:1) Mass spectrum (El): m/z = 329, 331 [M]+

(38) 1,3-dimethyl-7-(3-nitro-benzyl)-8-chloro-xanthine Carried out in the presence of potassium carbonate Rf value: 0.60 (silica gel, cyclohexane/ethyl acetate = 1:1) Mass spectrum (ESI+): m/z = 350, 352 [M+H]+
(39) 1,3-dimethyl-7-(4-nitro-benzyl)-8-chloro-xanthine Carried out in the presence of potassium carbonate Rf value: 0.60 (silica gel, cyclohexane/ethyl acetate = 1:1) (40) 3-methyl-7-(2-cyano-benzyl)-8-chloro-xanthine Rf value: 0.60 (silica gel, cyclohexane/ethyl acetate = 1:1) Mass spectrum (ESI+): m/z = 316, 318 [M+H]+
(41) 1,3-dimethyl-7-(2-nitro-benzyl)-8-chloro-xanthine Carried out in the presence of potassium carbonate Rf value: 0.60 (silica gel, cyclohexane/ethyl acetate = 1:1) (42) 1,3-dimethyl-7-(2-iod-benzyl)-8-chloro-xanthine Carried out in the presence of potassium carbonate.
Mass spectrum (ESI+): m/z = 431, 433 [M+H]+

Example II
(R)-1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-Digeridin-1-vll-xanthine A mixture of 1 g of 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-chloro-xanthine, 1.32 g of (R)-3-tert.-butyloxycarbonylamino-piperidine, 1 ml of triethylamine and 10 ml of dimethylformamide is stirred at 50 C for two and a half days. The reaction mixture is diluted with 100 ml of water and then extracted with ethyl acetate.
The organic phase is dried, evaporated down and the residue is stirred with diethylether.
The solid is suction filtered and dried.
Yield: 1.0 g (63 % of theory) Melting point: 164 C
Rf value: 0.36 (aluminium oxide, cyclohexane/ethyl acetate = 1:1) The following compounds are obtained analogously to Example II:

(1) (S)-1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Melting point: 164 C
Mass spectrum (ESI"): m/z = 445 [M-H]-(2) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-hexahydroazepin-1-yl]-xanthine Melting point: 154 C
Mass spectrum (ESI"): m/z = 459 [M-H]-(3) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-[4-(tert.-butyloxycarbonylamino)-hexahydroazepin-1-yl]-xanthine Mass spectrum (ESI'): rn/z = 459 [M-H]"
Rf value: 0.67 (silica gel, ethyl acetate) (4) 1,3-di methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylami no)-4-methyl-piperidin-1-yl]-xanthine Mass spectrum (ESI+): m/z = 461 [M+H]+
Rf value: 0.88 (silica gel, ethyl acetate/methanol = 5:1) (5) 1-methyl-3-(4-methoxy-benzyl)-7-benzyl-8-[(S')-3-(tent.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Mass spectrum (ESI+): m/z = 575 [M+H]+
Rf value: 0.74 (silica gel, methylene chloride/methanol = 95:5) (6) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-{N-[2-(tert.-butyloxycarbonylamino)-ethyl]-N-ethyl-amino}-xanthine Mass spectrum (ESI+): m/z = 435 [M+H]+

(7) 1-methyl -3-hexyl-7-benzyl-8-[(S)-3-(tert.-butyloxycarbonylamino)-piperidin- 1-yl]-xanthine Melting point: 152-159 C
Mass spectrum (ESI+): m/z = 539 [M+H]+

(8) 1-methyl-3-(2-trimethylsilanyl-ethoxymethyl)-7-benzyl-8-(3-amino-piperidin-1-yl)-xanthine Carried out with potassium carbonate at 120 C
Mass spectrum (ESI+): m/z = 485 [M+H]+
(9)1-methyl-3-(2-hydroxy-ethyl)-7-benzyl-8-[(S)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Carried out with potassium carbonate at 110 C
Rf value: 0.41 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
9:1:0.1) Mass spectrum (ESI+): m/z = 499 [M+H]+

(10) 1-(2-phenyl-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[(S)-3-(tert.-butyloxycarbonylamino)-piperidin-l-yl]-xanthine Carried out with Hunig base at 100 C
Mass spectrum (ESI+): m/z = 537 [M+H]+

(11) 1-(2-phenyl-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Mass spectrum (ESI+): m/z = 537 [M+H]+

(12) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-{2-[(tert.-butyloxycarbonylami no) methyl]-piperidin-l-yl}-xanthine Carried out with potassium carbonate and sodium iodide in dimethylsuiphoxide at Rf value: 0.73 (silica gel, ethyl acetate) Mass spectrum (ESI+): m/z = 461 [M+H]+

(13) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-{[1-(tert.-butyloxycarbonyl)-pyrrolidin-3-yl]amino}-xanthine Carried out with sodium carbonate in dimethylsuiphoxide at 130 C
Rf value: 0.50 (silica gel, ethyl acetate) Mass spectrum (ESI+): m/z = 433 [M+H]+

(14) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-{N-[1-(tert.-butyloxycarbonyl)-piperidin-3-yl]-N-methyl-amino}-xanthine Carried out with Hunig base, 4-dimethylaminopyridine and sodium carbonate in dimethylsulphoxide at 150 C
Rf value: 0.62 (silica gel, ethyl acetate) Mass spectrum (ESI+): rn/z = 461 [M+H]+

1001- (15) 3-methyl-7-(3-methyl-2-buten-1-yl)-8-[(S)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Rf value: 0.30 (silica gel, methylene chloride/methanol = 9:1) Mass spectrum (ESI+): rn/z = 433 [M+H]+

(16) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-{[1-(tert.-butyloxycarbonyl)-piperidin-4-yl]amino}-xanthine Carried out with Hunig base and 4-dimethylaminopyridine in dimethylsulphoxide at Rf value: 0.81 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
9:1:0.1) (17) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-{[1-(tert.-butyloxycarbonyl)-piperidin-3-yl]amino}-xanthine Carried out with Hunig base and 4-dimethylaminopyridine in dimethylsulphoxide at Rf value: 0.37 (silica gel, ethyl acetate/hexane = 7:3) (18) 3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Rf value: 0.49 (silica gel, petroleum ether/ethyl acetate/methanol = 5:4:1) Mass spectrum (ESI+): m/z = 433 [M+H]+

(19) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-{N-[1-(tert.-butyloxycarbonyl)-pyrrolidin-3-yl]-N-methyl-amino}-xanthine Carried out with sodium carbonate in dimethylsulphoxide at 160 C
Rf value: 0.68 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 447 [M+H]+

(20) 1-[2-(2-nitro-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Rf value: 0.34 (silica gel, petroleum ether/ethyl acetate/methanol = 7:2:1) Mass spectrum (ESI+): m/z = 582 [M+H]+

(21) 1-[2-(3,5-difluoro-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylami no)-piperidin-1-yl]-xanthine Rf value: 0.38 (silica gel, petroleum ether/ethyl acetate/methanol = 7:2:1) Mass spectrum (ESI+): m/z = 573 [M+H]+

(22) 1-[2-(2,6-difluoro-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Rf value: 0.38 (silica gel, petroleum ether/ethyl acetate/methanol = 7:2:1) Mass spectrum (ESI+): m/z = 573 [M+H]+

(23) 3-methyl-7-(3-methyl-2-buten-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Mass spectrum (ESI+): m/z = 433 [M+H]+

(24) 1-[2-(3,5-dimethyl-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Mass spectrum (ESI+): m/z = 565 [M+H]+

(25) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-[cis-2-(tert.-butyloxycarbonylamino)-cyclopropylami no]-xanthine R f value: 0.41 (silica gel, ethyl acetate) Mass spectrum (ESI+): m/z = 419 [M+H]+

(26) 3-methyl-7-(2-cyano-benzyl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Carried out with sodium carbonate in dimethylsulphoxide Mass spectrum (ESI-): m/z = 478 [M-H]-(27) 1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[4-(tert.-butyloxycarbonyl)-pipe razin-1-yl]=xanthine Carried out with potassium carbonate at 100 C
Rf value: 0.70 (silica gel, cyclohexane/ethyl acetate = 1:1) Mass spectrum (ESI+): m/z = 537 [M+H]+

(28) 1-[2-(3-nitro-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-l -yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-l -yl]-xanthine Mass spectrum (ESI+): m/z = 596 [M+H]+

(29) 1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[4-(tert.-butyloxycarbonyl)-homopiperazin-1-yl]-xanthine Rf value: 0.70 (silica gel, cyclohexane/ethyl acetate = 1:1) (30) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-{4-[(tert.-butyloxycarbonylamino)-methyl]-piperidin-1-yl}-xanthine Carried out in 1 -methyl-2-pyrroli done at 135 C.
Rf value: 0.69 (silica gel, ethyl acetate) Mass spectrum (ESI+): rn/z = 461 [M+H]+

(31) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-{3-[(tert.-butyloxycarbonylamino)-methyl]-piperidin-1-yl}-xanthine Carried out in 1 -methyl-2-pyrrolidone at 135 C.
Rf value: 0.74 (silica gel, ethyl acetate) Mass spectrum (ESI+): rn/z = 461 [M+H]+

(32) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-[trans-2-(tert.-butyloxycarbonylamino)-cyclobutylamino]-xanthine Carried out in the presence of Hunig base in 1-methyl-2-pyrrolidone at 135 C.
Rf value: 0.65 (silica gel, ethyl acetate/petroleum ether = 8:2) Mass spectrum (ESI+): m/z = 433 [M+H]+

(33) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-{N-[(S)-2-(tert.-butyloxycarbonylamino)-1-methyl-ethyl]-N-methyl-amino}-xanthine Carried out with sodium carbonate in dimethylsulphoxide Rf value: 0.69 (silica gel, ethyl acetate) Mass spectrum (ESI+): m/z = 435 [M+H]+

(34) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-{N-[(R)-2-(tert.-butyloxycarbonylamino)-1-methyl-ethyl]-N-methyl-amino}-xanthine Carried out with sodium carbonate in dimethylsulphoxide Rf value: 0.32 (silica gel, cyclohexane/ethyl acetate = 1:1) Mass spectrum (ESI+): m/z = 435 [M+H]+

(35) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-[cis-2-(tert.-butyloxycarbonylamino)-cyclohexylami no]-xanthi ne Carried out with sodium carbonate in dimethylsulphoxide Rf value: 0.35 (silica gel, cyclohexane/ethyl acetate = 1:1) Mass spectrum (ESI+): rn/z = 461 [M+H]+

(36) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-[6-(tert.-butyloxycarbonylamino)-[1,4]diazepan-1-yl]-xanthine Carried out with sodium carbonate in dimethylsulphoxide Rf value: 0.08 (silica gel, methylene chloride/methanol = 95:5) (37) 1-[(pyridin-2-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylami no)-piperidin-1-yl]-xanthine Carried out with sodium carbonate in dimethylsuiphoxide Rf value: 0.43 (silica gel, ethyl acetate) Mass spectrum (ESI+): m/z = 524 [M+H]+

(38) 1,3-di methyl-7-(3-methyl-2-buten- 1 -yl) -8-[trans-2- (tert.-butyl oxycarbonyl amino)-cyclopentylamino]-xanthine Carried out in the presence of Hunig base in 1-methyl-2-pyrrolidone at 135 C.
Melting point: 177-179 C
Mass spectrum (ESI+): m/z = 447 [M+H]+

(39) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-cyclohexylamino]-xanthine (cis/trans mixture) Carried out in the presence of Hunig base in 1-methyl-2-pyrrolidone at 135 C.
Rf value: 0.36 (silica gel, ethyl acetate/petroleum ether = 1:1) Mass spectrum (ESI"): m/z = 459 [M-H]-(40) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-[cis-2-(tert.-butyloxycarbonylamino)-cyclopentylami no]-xanthine " Melting point: 175-178 C
Mass spectrum (ESI"): m/z = 445 [M-H]-(41) 1-[(isoquinolin-1-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-pipendin-1-yl]-xanthine Carried out with sodium carbonate in dimethylsuiphoxide Rf value: 0.51 (silica gel, methylene chloride/methanol = 95:5) (42) 1,3-dimethyl-7-(3-methyl-2-buten-1 -yl)-8-[cis-3-(tert.-butyloxycarbonylamino)-cyclopentylamino]-xanthine Carried out in the presence of Hunig base in 1-methyl-2-pyrrolidone at 135 C.
Rf value: 0.23 (silica gel, ethyl acetate/petroleum ether = 1:1) Mass spectrum (ESI+): m/z = 447 [M+H]+
(43) 1-[(pyridin-3-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Carried out with sodium carbonate in dimethylsulphoxide Rf value: 0.44 (silica gel, methylene chloride/methanol = 95:5) Mass spectrum (ESI+): m/z = 524 [M+H]+
(44) 1-[(pyridin-4-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Carried out with sodium carbonate in dimethylsulphoxide Rf value: 0.28 (silica gel, ethyl acetate) Mass spectrum (ESI+): m/z = 524 [M+H]+
(45) 1-[(isoquinolin-1-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylami no)-piperidin-1-yl]-xanthine Carried out with potassium carbonate in dimethylsulphoxide Rf value: 0.37 (silica gel, ethyl acetate) Mass spectrum (ESI+): nVz = 574 [M+H]+
(46) 1-[(isoquinolin-1-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[(S)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl}-xanthine Carried out with potassium carbonate in dimethylsulphoxide Rf value: 0.37 (silica gel, ethyl acetate) Mass spectrum (ESI+): m/z = 574 [M+H]+
(47) 1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-3-methyl-piperidin-1-yl]-xanthine Rf value: 0.51 (silica gel, cyclohexane/ethyl acetate/methanol = 6:3:1) Mass spectrum (ESI+): m/z = 565 [M+H]+
(48) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-methyl-piperidin-1-yl]-xanthine Rf value: 0.48 (silica gel, cyclohexane/ethyl acetate/methanol = 6:3:1) Mass spectrum (El): rn/z = 460 [M]+
(49) 1,3-dimethyl-7-(3-methyl-2-buten-l-yl)-8-{N-[2-(tert.-butyloxycarbonylamino)-3-d imethyl ami no-3-oxo-p ropyl]- N-methyl-ami n o}-xanthine Rf value: 0.48 (silica gel, methylene chloride/methanol = 9:1) Mass spectrum (ESI+): m/z = 492 [M+H]+
(50) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-{N-[2-(tart.-butyloxycarbonylamino)-3-ami no-3-oxo-p ropyl]-N-methyl-ami no}-xanthine Rf value: 0.40 (silica gel, methylene chloride/methanol = 9:1) Mass spectrum (El): m/z = 463 [M]+
(51) 1-[2-(2-nitro-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-l-yl]-xanthine Carried out with sodium carbonate in dimethylsulphoxide.
Mass spectrum (ESI+): m/z = 596 [M+H]+
(52) 1-[(isoquinolin-4-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Carried out with sodium carbonate in dimethylsulphoxide.
Rf value: 0.48 (silica gel, ethyl acetate) Mass spectrum (ESI+): m/z = 574 [M+H]+
(53) 1-[(1-methyl-l H-indazol-3-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylami no)-piperidin-1-yl]-xanthine Carried out with sodium carbonate in dimethylsulphoxide.
Mass spectrum (ESI+): m/z = 577 [M+H]+
(54) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-{N-[2-(tert.-butyloxycarbonylamino)-3-oxo-3-(pyrrolidin-1-yl)-propyl]-N-methyl-amino}-xanthine Carried out with Hunig base in N-methylpyrrolidinone.
Melting point: 173-175 C
Mass spectrum (ESI+): m/z = 518 [M+H]+
(55) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-{N-[2-(tert.-butyloxycarbonylamino)-3-methylami no-3-oxo-propyl]-N-methyl-amino}-xanthine Carried out with Hunig base in N-methylpyrrolidinone.
Mass spectrum (ESI+): m/z = 478 [M+H]+
(56) 1-[2-(2-hydroxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin Mass spectrum (ESI+): rn/z = 567 [M+H]+
(57) 1-methyl-3-[2-(4-methoxy-phenyl)-ethyl]-7-(2-cyano-benzyl)-8-[3-(tert.-butyloxy-carbonylamino)-piperidin-1-yl]-xanthin Carried out in the presence of sodium carbonate in dimethylsulphoxide.
Rf value: 0.50 (silica gel, methylene chloride/methanol = 9:1) Mass spectrum (ESI+): m/z = 614 [M+H]+
(58) 1-methyl-3-(2-phenyl-ethyl)-7-(2-cyano-benzyl)-8-[3-(tert.-butyloxycarbonyl-amino)-piperidin-1-yl]-xanthine Carried out in the presence of sodium carbonate in dimethylsulphoxide.
Mass spectrum (ESI+): m/z = 584 [M+H]+
(59) 1-[(quinolin-4-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxy-carbonylamino)-piperidin-1-yl]-xanthine Carried out in the presence of sodium carbonate in dimethylsulphoxide.
Rf value: 0.50 (silica gel, ethyl acetate) Mass spectrum (ESI+): m/z = 574 [M+H]+
(60) 1,3-dimethyl-7-(3-methyl-2-buten-l-yl)-8-[endo-6-(tert.-butyloxycarbonylamino)-2-aza-bicyclo[2.2.2]oct-2-yl]-xanthi n e Carried out in the presence of potassium carbonate and Hunig base in dimethylsulphoxide.
Rf value: 0.52 (silica gel, cyclohexane/ethyl acetate = 1:1) Mass spectrum (ESI+): m/z = 473 [M+H]+
(61) 1-[(quinolin-8-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yi)-8-[3-(tert.-butyloxy-carbonylami no)-piperidin-1-yl]-xanthine Carried out in the presence of sodium carbonate in dimethylsulphoxide.
Rf value: 0.73 (silica gel, ethyl acetate) Mass spectrum (ESI+): rn/z = 574 [M+H]+
(62) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-[exo-6-(tert.-butyloxycarbonylamino)-2-aza-bicyclo[2.2.2]oct-2-yl]-xanthine Carried out in the presence of potassium carbonate and Hunig base in dimethylsulphoxide.
Rf value: 0.45 (silica gel, cyclohexane/ethyl acetate = 1:1) Mass spectrum (ESI+): m/z = 473 [M+H]+
(63) 1-[2-(3-cyano-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-l -yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-l-yl]-xanthine Carried out in the presence of sodium carbonate in dimethylsulphoxide.
Rf value: 0.33 (silica gel, cyclohexane/ethyl acetate = 1:1) Mass spectrum (ESI+): m/z = 576 [M+H]+
(64) 1-[2-(3-aminosulphonyl-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-l-yl]-xanthine Carried out in the presence of sodium carbonate in dimethylsulphoxide.
Rf value: 0.15 (silica gel, cyclohexane/ethyl acetate = 1:1) Mass spectrum (ESI"): rn/z = 628 [M-H]"
(65) 1-[2-(3-aminocarbonyl-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tart.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Carried out in the presence of sodium carbonate in dimethylsulphoxide.
Rf value: 0.36 (silica gel, methylene chloride/methanol = 9:1) Mass spectrum (ESI+): rr/z = 594 [M+H]+

Example III
3-(tert.-butvloxvcarbonvlamino -hexahydroazepine 2,g of 1 -benzyl-3-(tert.-butyloxycarbonylamino)-hexahydroazepine in 20 ml of methanol are hydrogenated for 24 hours at ambient temperature under a hydrogen pressure of 3 bar in the presence of 200 mg palladium on activated charcoal (10%
Pd). Then the catalyst is removed by suction filtering and the filtrate is evaporated to dryness.
Yield: 1.3 g (90 % of theory) Melting point: 78 C
Mass spectrum (ESI+): m/z = 215 [M+H]+

The following compounds are obtained analogously to Example III:
(1) (S)-3-(tert.-butyloxycarbonylamino)-piperidine Melting point: 122 C
Mass spectrum (ESI+): rn/z = 201 [M+H]+

(2) (R)-3-(tert.-butyloxycarbonylamino)-piperidine The starting material, (R)-1 -benzyl-3-(tert.-butyloxycarbonylamino)-piperidine, was prepared analogously to the (S)-enantiomer known from the literature (Moon, Sung-Hwan; Lee, Sujin; Synth.Commun.; 28; 21; 1998; 3919-3926) Melting point: 119 C
Mass spectrum (ESI+): m/z = 201 [M+H]+

(3) 4-(tert.-butyloxycarbonylamino)-hexahydroazepine Mass spectrum (ESI+): m/z = 215 [M+H]+

Rf value: 0.02 (aluminium oxide, cyclohexane/ethyl acetate = 1:1) (4) 3-(tert.-butyloxycarbonylamino)-4-methyl-piperidine The crude product is further reacted directly to form the compound of Example II (4).
(5) 6-(tert.-butyloxycarbonylamino)-[1,4]diazepan The starting material 1,4-dibenzyl-6-(tert.-butyloxycarbonylamino)-[1,4]diazepan was prepared analogously to J. heterocyci. Chem. 1995, 32, 637-642.
The crude product is further reacted directly to form the compound of Example II
(36).

(6) 2-(tert.-butyloxycarbonylamino)-3-methylamino-propionic acid-dimethylamide Rf value: 0.40 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
40:10:1) Mass spectrum (ESI+): m/z = 246 [M+H]+

(7) 2-(tert.-butyloxycarbonylamino)-3-methylamino-propionic acid-amide Rf value: 0.20 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
40:10:1) Mass spectrum (ESI+): m/z = 218 [M+H]+

(8) 2-(tert.-butyl oxycarbonylamino)-3-methylamino- 1-(pyrrolidin-1-yl)-propan-l -one Palladium([I)hydroxide is used as catalyst.
Mass spectrum (ESI+): m/z = 272 [M+H]+

(9) 2-(tert.-butyloxycarbonylamino)-1,3-bis(methylamino)-propan-1-one Palladium(ll)hydroxide is used as catalyst.
Mass spectrum (ESI+): m/z = 232 [M+H]+

(10) endo-6-(tert.-Butyloxycarbonylamino)-2-aza-bicyclo[2.2.2]octan Rf value: 0.25 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:0.1) Mass spectrum (ESI+): m/z = 227 [M+H]+

(11) exo-6-(tert.-butyloxycarbonylamino)-2-aza-bicyclo[2.2.2]octane Rf value: 0.27 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) (12) 1-(tert.-butyloxycarbonyl)-3-amino-4-hydroxy-piperidin Rf value: 0.17 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 217 [M+H]+
Example IV
1 -benzyl-3-(tert-butyloxvcarbonylamino)-hexahydroazepine Prepared by reacting 1-benzyl-3-amino-hexahydroazepine with di-tert.butyl pyrocarbonate Melting point: 48-50 C
Mass spectrum (ESI+): m/z = 305 [M+H]+

The following compounds are obtained analogously to Example IV:
(1) 1-benzyl-4-(tert.-butyloxycarbonylamino)-hexahydroazepine Mass spectrum (ESI+): m/z = 305 [M+H]+
Rf value: 0.79 (aluminium oxide, cyclohexane/ethyl acetate = 1:1) (2) 3-(tert.-butyloxycarbonylamino)-4-methyl-pyridine Carried out with sodium-bis-(trimethylsilyl)-amide/di-tert.butyl pyrocarbonate in tetrahydrofuran at 0 C.
Rf value: 0.45 (silica gel, ethyl acetate) (3) 1-(tert.-butyloxycarbonyl)-3-[(2,2,2-trifluoro-acetyl)amino]-pyrrolidine Carried out with triethylamine in tetrahydrofuran Rf value: 0.77 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 281 [M+H]+

(4) trans-2-amino-l-(tert.-butyloxycarbonylamino)-cyclobutane Carried out with di-tert.butyl pyrocarbonate in the presence of 1 N sodium hydroxide solution in methanol at 0 C.
Rf value: 0.60 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:0.1) Mass spectrum (ESI+): m/z = 187 [M+H]+

(5) (S)- 1-(tert.-butyloxycarbonylami no)-2-methylami no-propane Carried out with di-tert.butyl pyrocarbonate in the presence of Hunig base in methanol.
Mass spectrum (ESI+): m/z = 189 [M+H]+
Rf value: 0.30 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) (6) (R)-1-(tert.-butyloxycarbonylamino)-2-methylamino-propane Carried out with di-tert.butyl pyrocarbonate in the presence of Hunig base in methanol.
Mass spectrum (ESI'): m/z = 189 [M+H]+

(7) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-[2-(tert.-butyloxycarbonylamino)-methyl-propylamino]-xanthine Carried out with di-tert.butyl pyrocarbonate in the presence of Hunig base in methanol.
Rf value: 0.82 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) (8) cis-3-amino-l-(tert.-butyloxycarbonylamino)-cyclopentane Carried out with di-tert.butyl pyrocarbonate in the presence of 1 N sodium hydroxide solution in methanol.
Rf value: 0.63 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
40:10:1) Mass spectrum (ESI+): rn/z = 201 [M+H]+

(9) endo-6-(tert.-butyloxycarbonylamino)-2-benzyl-2-aza-bicyclo[2.2.2]octane Rf value: 0.53 (aluminium oxide, cyclohexane/ethyl acetate = 9:1) Mass spectrum (ESI+): m/z = 317 [M+H]+

(10) exo-6-(tert.-butyloxycarbonylamino)-2-benzyl-2-aza-bicyclo[2.2.2]octane Rf value: 0.37 (aluminium oxide, cyclohexane/ethyl acetate = 9:1) Mass spectrum (ESI+): m/z = 317 [M+H]+
Example V
1.3-dimethyl-8-(cis-3-tert.-butvloxycarbonvlamino-c cIY ohexyl)-xanthine Prepared from the compound of Example VI by treating with 4N sodium hydroxide solution in methanol at 100 C in a bomb tube Mass spectrum (ESI+): m/z = 378 [M+H]+

The following compound is obtained analogously to Example V:
(1) 1,3-dimethyl-8-[3-(tert.-butyloxycarbonylamino)propyl]-xanthine Mass spectrum (ESI+): m/z = 338 [M+H]+

(2) 1,3-dimethyl-8-[1-(tert.-butyloxycarbonyl)-piperidin-4-yl]-xanthine (3) 1,3-dimethyl-8-[ trans-2-(tert.-butyloxycarbonylamino)-cyclohexyl]-xanthine Mass spectrum (ESI+): rn/z = 378 [M+H]+

(4) 1,3-dimethyl-8-[3-(tert.-butyloxycarbonylamino)-cyclohexyl]-xanthine (cis/trans mixture) Mass spectrum (ESI+): m/z = 378 [M+H]+

(5) 1,3-dimethyl-8-[1-(tert.-butyloxycarbonyl)-piperidin-3-yl]-xanthine Mass spectrum (ESI+): m/z = 364 [M+H]+

Example VI
1,3-dimethyl-5-[(cis-3-tert.-butyloxycarbonylamino-cyclohexyl)-carbonylamino]-amino-uracil Prepared from 5,6-diamino-1,3-dimethyluracil and cis-3-tert.-butyloxycarbonylamino-cyclohexanecarboxylic acid in the presence of O-(benzotriazol-1-yl)-N,N,N`,N`-tetramethyluronium hexafluorophosphate and N-ethyl-diisopropylamine in dimethylformamide at ambient temperature Mass spectrum (ESI+): rn/z = 396 [M+H]+

The following compound is obtained analogously to Example VI:

(1) 1,3-dimethyl-5-{[3-(tert.-butyloxycarbonylamino)propyl]-carbonylamino}-6-amino-uracil (2) 1,3-dimethyl-5-{[1-(tert.-butyloxycarbonyl)-piperidin-4-yl]-carbonylamino}-amino-uracil Carried out with O-(benzotriazol-1-yl)-N,N,N`,N`-tetramethyluronium tetrafluoroborate and N-hydroxybenzotriazole Mass spectrum (ESI+): m/z = 382 [M+H]+

(3) 1,3-dimethyl-5-({trans-2-[(fluoren-9-ylmethoxycarbonyl)amino]-cyclohexyl}-carbonylamino)-6-amino-uracil Carried out with 0-(benzotriazol-1-yi)-N,N,N`,N`-tetramethyluronium tetrafluoroborate Mass spectrum (ESI+): rn/z = 518 [M+H]+

(4) 1,3-dimethyl-5-{[3-(tert.-butyloxycarbonylamino)-cyclohexyl]-carbonylamino}-6-amino-uracil (cis/trans mixture) Carried out with O-(benzotriazol-1-yl)-N,N,N`,N`-tetramethyluronium tetrafluoroborate Mass spectrum (ESI+): m/z = 396 [M+H]+

(5) 1,3-dimethyl-5-{[1-(tert.-butyloxycarbonyl)-piperidin-3-yl]-carbonylamino}-amino-uracil Carried out with O-(benzotriazol-1-yl)-N,N,N`,N`-tetramethyluronium tetrafluoroborate Mass spectrum (ESI+): m/z = 382 [M+H]+

(6) 2-(tert.-butyloxycarbonylamino)-3-(N-benzyl-N-methyl-amino)-propionic acid-dimethylamide Carried out with dimethylamine in the presence of O-(benzotriazol-1-yl)-N,N,N`,N`-tetramethyluronium tetrafluoroborate and hydroxybenzotriazole in tetrahydrofuran.
Rf value: 0.80 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
40:10:1) Mass spectrum (ESI+): m/z = 336 [M+H]+

(7) 2-(tert.-butyloxycarbonylamino)-3-(N-benzyl-N-methyl-amino)-propionic acid-amide Carried out with ammonium carbonate in the presence of O-(benzotriazol-1-yl)-N,N,N`,N`-tetramethyluronium tetrafluoroborate and hydroxybenzotriazole in tetrahydrofuran.
Rf value: 0.75 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
40:10:1) Mass spectrum (ESI+): m/z = 308 [M+H]+

(8) 2-(tert.-butyloxycarbonylamino)-3-(N-benzyl-N-methyl-amino)-1-(pyrrolidin-l -yl)-propane-l-one Carried out with pyrrolidine in the presence of O-(benzotriazol-1-yl)-N,N,N`,N`-tetramethyluronium tetrafluoroborate and hydroxybenzotriazole in tetrahydrofuran.
Rf value: 0.40 (silica gel, methylene chloride/methanol = 9:1) Mass spectrum (ESI+): m/z = 362 [M+H]+

(9) 2-(tert.-butyloxycarbonylamino)-3-(N-benzyl-N-methyl-amino)-1-dimethylamino-propane-1-one Carried out with methylamine (40% aqueous solution) in the presence of 0-(benzotriazol-1-yi)-N,N,N`,N`-tetramethyluronium tetrafluoroborate and hydroxybenzotriazole in tetrahydrofuran.
Rf value: 0.40 (silica gel, methylene chloride/methanol = 9:1) Mass spectrum (ESI+): m/z = 322 [M+H]+

(10) 1-(tert.-butyloxycarbonyl)-3-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}-3-(pyrrolidin-1-ylcarbonyl)-piperidine Carried out with pyrrolidine in the presence of 0-(benzotriazol-1-yl)-N,N,N`,N`-tetra-methyluronium tetrafluoroborate, hydroxybenzotriazole and Honig base in dimethyl-formamide. The starting material 1-(tert.-butyloxycarbonyl)-3-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}-piperidin-3-yl-carboxylic acid is obtainable from Pharmacore, Inc. (USA).
Rf value: 0.52 (aluminium oxide, methylene chloride/methanol = 9:1) Mass spectrum (ESI+): m/z = 520 [M+H]+

Example VII
1,3-bis-(cyclopropylmethyl)-7-benzvl-8-chloro-xanthine Prepared from the compound of Example VIII by refluxing with N-chlorosuccinimide in 1,2-dichloroethane.
Mass spectrum (ESI+): m/z = 407, 409 [M+Na]+

The following compounds are obtained analogously to Example VII:
(1) 1-methyl-3-(cyclopropylmethyl)-7-benzyl-8-chloro-xanthine Mass spectrum (ESI+): m/z = 345, 347 [M+H]+

(2) 1,3-diethyl-7-benzyl-8-chloro-xanthine Mass spectrum (ESI+): rn/z = 355, 357 [M+NaJ+

(3) 1-methyl-3-ethyl-7-benzyl-8-chloro-xanthine Mass spectrum (ESI+): m/z = 341, 343 [M+Na]+

(4) 1-methyl-3-(4-methoxy-benzyl)-7-benzyl-8-chloro-xanthine Melting point: 172-175 C
Mass spectrum (ESI+): rn/z = 411, 413 [M+H]+
(5) 1-methyl-3,7-dibenzyl-8-chloro-xanthine Rf value: 0.72 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
98:2:1) Mass spectrum (ESI+): m/z = 381, 383 [M+H]+

(6) 1-methyl-3-[(methoxycarbonyl)-methyl]-7-benzyl-8-chloro-xanthine Rf value: 0.83 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
95:5:1) Mass spectrum (ESI+): m/z = 363, 365 [M+H]+

(7) 1-methyl-3-isopropyl-7-benzyl-8-chloro-xanthine Rf value: 0.69 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
98:2:1) Mass spectrum (El): m/z = 332, 334 [M]+

(8) 1-methyl-3-hexyl-7-benzyl-8-chloro-xanthine Rf value: 0.68 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
98:2:1) Mass spectrum (ESI+): m/z = 375, 377 [M+H]+

(9) 1-methyl-3-(2-trimethylsilanyl-ethoxymethyl)-7-benzyl-8-chloro-xanthine Mass spectrum (ESI+): m/z = 421, 423 [M+H]+

(10) 1-methyl-3-(2-methoxy-ethyl)-7-benzyl-8-chloro-xanthine Rf value: 0.84 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
9:1:0.1) Mass spectrum (ESI+): m/z = 349, 351 [M+Hj+

(11) 1-methyl-3-cyanomethyl-7-benzyl-8-chloro-xanthine Rf value: 0.90 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
95:5:1) Mass spectrum (ESI+): m/z = 352 [M+Na]+

(12) 1-methyl-3-(2-hydroxy-ethyl)-7-benzyl-8-chloro-xanthine Rf value: 0.48 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
9:1:0.1) Mass spectrum (ESI+): m/z = 335, 337 [M+H]+

(13) 1-methyl-3-(2-trimethylsilanyl-ethoxymethyl)-7-benzyl-8-chloro-xanthine Mass spectrum (ESI+): m/z = 421, 423 [M+H]+

(14) 1-methyl-3-(2-trimethylsilanyl-ethoxymethyl)-7-(2-cyano-benzyl)-8-chloro-xanthine Mass spectrum (ESI+): m/z = 468, 470 [M+Na]+
Example VIII
1.3-bis- cyclopropylmethyl)-7-benzyl-xanthine Prepared from 7-benzyl-xanthine by reacting with cyclopropyl methyl bromide in dimethylformamide in the presence of caesium carbonate Mass spectrum (ESI+): m/z = 351 [M+H]+

The following compounds are obtained analogously to Example VIII:
(1) 3-(cyclopropytmethyl)-7-benzyl-xanthine Mass spectrum (ESI+): m/z = 297 [M+H]+

(2) 1,3-diethyl-7-benzyl-xanthine Carried out with potassium carbonate Mass spectrum (ESI+): m/z = 321 [M+Na]+
(3) 3-ethyl-7-benzyl-xanthine Carried out with potassium carbonate Mass spectrum (ESI+): m/z = 293 [M+Na]+
(4) 3-(4-methoxy-benzyl)-7-benzyl-xanthine Carried out with 1,8-diazabicyclo[5.4.0]undec-7-ene Mass spectrum (ESI+): m/z = 363 [M+H]+

(5) 3,7-dibenzyl-xanthine Carried out with 1,8-diazabicyclo[5.4.0]undec-7-ene Melting point: 184-187 C
Mass spectrum (ESI+): m/z = 333 [M+H]+

(6) 3-[(methoxycarbonyl)-methyl]-7-benzyl-xanthine Carried out with 1,8-diazabicyclo[5.4.0]undec-7-ene Rf value: 0.21 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
95:5:1) Mass spectrum (ESI+): m/z = 315 [M+H]+
(7) 3-isopropyl-7-benzyl-xanthine Carried out with 1,8-diazabicyclo[5.4.0]undec-7-ene Melting point: 215-218 C
Mass spectrum (ESI+): m/z = 285 [M+H]+
(8) 3-hexyl-7-benzyl-xanthine Carried out with 1,8-diazabicyclo[5.4.0]undec-7-ene Rf value: 0.52 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
9:1:0.1) Mass spectrum (ESI+): mlz = 327 [M+H]+

(9) 3-(2-trimethylsilanyi-ethoxymethyl)-7-benzyl-xanthine Carried out with 1,8-diazabicyclo[5.4.0]undec-7-ene Mass spectrum (ESI+): m/z = 373 [M+H]+

(10) 3-(2-methoxy-ethyl)-7-benzyl-xanthine Carried out with 1,8-diazabicyclo[5.4.0]undec-7-ene Rf value: 0.45 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
9:1:0.1) Mass spectrum (ESI+): m/z = 301 [M+H]+
(11) 3-cyanomethyl-7-benzyl-xanthine Carried out with 1,8-diazabicyclo[5.4.0]undec-7-ene Rf value: 0.41 (silica gel, methylene chioride/methanol/conc. aqueous ammonia =
9:1:0.1) Mass spectrum (ESI"): m/z = 280 [M-H]-(12) 3-(2-hydroxy-ethyl)-7-benzyl-xanthine Carried out with 1,8-diazabicyclo[5.4.0]undec-7-ene Rf value: 0.28 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
9:1:0.1) Mass spectrum (ESI+): m/z = 287 [M+H]+

(13) 3-(2-trimethylsilanyl-ethoxymethyl)-7-benzyl-xanthine Carried out with 1,8-diazabicyclo[5.4.0]undec-7-ene Rf value: 0.30 (silica gel, methylene chloride/methanol = 98:2) Mass spectrum (ESI+): m/z = 373 [M+H]+

(14) 3-[(methoxycarbonyl)methyl]-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Carried out with 1,8-diazabicyclo[5.4.0]undec-7-ene Rf value: 0.31 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 491 [M+H]+

(15) 3-(2-trimethylsilanyl-ethoxymethyl)-7-(2-cyano-benzyl)-xanthine Carried out in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene.
Mass spectrum (ESI+): m/z = 420 [M+Na]+

Example IX
1-ethyl-3-methyl-7-(3-methyl-2-buten-1-vl)-8-bromo-xanthine Prepared from 3-methyl-7-(3-methyl-2-buten-1-yl)-8-bromo-xanthine by reacting with ethyl bromide in the presence of potassium carbonate in dimethylformamide at Mass spectrum (ESI+): m/z = 341, 343 [M+H]+
Retention time: 1.48 min (HPLC, Multosphere 100FBS, 50 mm, 50% acetonitrile) The following compounds are obtained analogously to Example IX:

(1) 1-propyl-3-methyl-7-(3-methyl-2-buten-1-yl)-8-bromo-xanthine Mass spectrum (ESI+): m/z = 355, 357 [M+H]+

(2) 1-butyl-3-methyl-7-(3-methyl-2-buten-1-yl)-8-bromo-xanthine Mass spectrum (ESI+): m/z = 369, 371 [M+H]+

(3) 1-(2-propyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-bromo-xanthine Retention time: 2.11 min (HPLC, Multosphere 100FBS, 50 mm, 50% acetonitrile) (4) 1-(2-methylpropyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-bromo-xanthine Retention time: 2.46 min (HPLC, Multosphere 100FBS, 50 mm, 50% acetonitrile) (5) 1-(2-propen-1-yl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-bromo-xanthine Retention time: 1.55 min (HPLC, Multosphere 100FBS, 50 mm, 50% acetonitrile) Mass spectrum (ESI+): m/z = 353, 355 [M+H]+

(6) 1-(2-propyn-1-yl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-bromo-xanthine Retention time: 1.20 min (HPLC, Multosphere 100FBS, 50 mm, 50% acetonitrile) Mass spectrum (ESI+): m/z = 351, 353 [M+H]+

(7) 1-(cyclopropylmethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-bromo-xanthine Retention time: 2.19 min (HPLC, Multosphere 100FBS, 50 mm, 50% acetonitrile) Mass spectrum (ESI+): m/z = 367, 369 [M+H]+

(8) 1-benzyl-3-methyl-7-(3-methyl-2-buten-1-yl)-8-bromo-xanthine Retention time: 2.40 min (HPLC, Multosphere 100FBS, 50 mm, 50% acetonitrile) Mass spectrum (ESI+): m/z = 403, 405 [M+H]+

(9) 1-(2-phenylethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-bromo-xanthine Retention time: 3.29 min (HPLC, Multosphere 100FBS, 50 mm, 50% acetonitrile) (10) 1-(3-phenylpropyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-bromo-xanthine Retention time: 2.95 min (HPLC, Multosphere 100FBS, 50 mm, 50% acetonitrile) (11) 1-(2-hydroxyethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-bromo-xanthine Retention time: 2.35 min (HPLC, Multosphere 100FBS, 50 mm, 20% acetonitrile) (12) 1-(2-methoxyethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-bromo-xanthine Retention time: 2.54 min (HPLC, Multosphere 100FBS, 50 mm, 30% acetonitrile) (13) 1-(3-hydroxypropyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-bromo-xanthine Retention time: 2.52 min (HPLC, Multosphere 100FBS, 50 mm, 20% acetonitrile) (14) 1-[2-(dimethylamino)ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-bromo-xanthine Retention time: 2.73 min (HPLC, Multosphere 100FBS, 50 mm, 5% acetonitrile) (15) 1-[3-(dimethylamino)propyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-bromo-xanthine Retention time: 2.79 min (HPLC, Multosphere 100FBS, 50 mm, 5% acetonitrile) (16) 1-methyl-3-(cyclopropylmethyl)-7-benzyl-xanthine Carried out with methyl iodide at ambient temperature Mass spectrum (ESI+): m/z = 311 [M+H]+

(17) 1-methyl-3-ethyl-7-benzyl-xanthine Carried out with methyl iodide at ambient temperature (18) 1-methyl-3-(4-methoxy-benzyl)-7-benzyl-xanthine Carried out with methyl iodide at ambient temperature Mass spectrum (ESI+): m/z = 377 [M+H]+

(19) 1-methyl-3,7-dibenzyl-xanthine Carried out with methyl iodide at ambient temperature Rf value: 0.51 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
95:5:1) Mass spectrum (ESI+): m/z = 347 [M+H]+

(20) 1-methyl-3-[(methoxycarbonyl)-methyl]-7-benzyl-xanthine Carried out with methyl iodide at ambient temperature Melting point: 182 C
Mass spectrum (ESI+): m/z = 329 [M+H]+
(21) 1-methyl-3-isopropyl-7-benzyl-xanthine Carried out with methyl iodide at ambient temperature Rf value: 0.66 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
9:1:0.1) Mass spectrum (ESI+): m/z = 299 [M+H]+

(22) 1-methyl-3-hexyl-7-benzyl-xanthine Carried out with methyl iodide at ambient temperature Rf value: 0.77 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
95:5:1) Mass spectrum (ESI+): m/z = 341 [M+H]+

(23) 1-methyl-3-(2-trimethylsilanyl-ethoxymethyl)-7-benzyl-xanthine Carried out with methyl iodide at ambient temperature (24) 1-methyl-3-(2-methoxy-ethyl)-7-benzyl-xanthine Carried out with methyl iodide at ambient temperature Rf value: 0.70 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
9:1:0.1) Mass spectrum (ESI+): m/z = 315 [M+H]+

(25) 1-methyl-3-cyanomethyl-7-benzyl-xanthine Carried out with methyl iodide at ambient temperature Rf value: 0.74 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
9:1:0.1) Mass spectrum (ESI+): m/z = 296 [M+H]+

(26) 1-methyl-3-(2-hydroxy-ethyl)-7-benzyl-xanthine Carried out with methyl iodide at ambient temperature Rf value: 0.44 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
9:1:0.1) Mass spectrum (ESI+): m/z = 301 [M+H]+

(27) 1-methyl-3-(2-trimethylsilanyl-ethoxymethyl)-7-benzyl-xanthine Carried out with methyl iodide at ambient temperature Rf value: 0.44 (silica gel, methylene chloride/methanol = 95:5) Mass spectrum (ESI+): m/z = 387 [M+H]+

(28) 1-(2-phenyl-ethyl)-3-methyl-7-benzyl-8-chloro-xanthine Carried out with 2-phenyl-ethyl bromide at 60 C
Mass spectrum (ESI+): rn/z = 395, 397 [M+H]+

(29) 1-(2-phenyl-ethyl)-3-methyl-7-cyclopropylmethyl-8-chloro-xanthine Carried out with 2-phenyl-ethyl bromide at 60 C
Mass spectrum (ESI+): m/z = 359, 361 [M+H]+

(30) 1-(2-phenyl-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-chloro-xanthine Mass spectrum (ESI+): m/z = 357, 359 [M+H]+

(31) 1-(2-phenyl-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-chloro-xanthine Mass spectrum (ESI+): rrVz = 395, 397 [M+Na]+

(32) 1-[(methoxycarbonyl)-methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[(S)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Carried out with methyl bromoacetate at 50 C
Melting point: 143-145 C
Mass spectrum (ESI+): n1/z = 505 [M+H]+

100' (33) 1-[3-(methoxycarbonyl)-propyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[(S)-3-(tert: butyloxycarbonylamino)-piperidin-1-yl]-xanthine Carried out with methyl 4-bromobutyrate at 50 C
Melting point: 130-131 C
Mass spectrum (ESI+): m/z = 533 [M+H]+

(34) 1-{2-[4-(ethoxycarbonyl)-phenyl]-ethyl}-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[(S)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Carried out with ethyl 4-(2-bromo-ethyl)-benzoate at 50 C
Rf value: 0.40 (silica gel, cyclohexane/ethyl acetate = 1:1) Mass spectrum (ESI+): m/z = 609 [M+H]+

(35) 1-[2-(methoxycarbonyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[(S')-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Carried out with methyl 3-bromopropionate at 50 C
Rf value: 0.35 (silica gel, cyclohexane/ethyl acetate = 1:1) Mass spectrum (ESI+): m/z = 519 [M+H]+

(36) 1-cyanomethyl-3-methyl-7-(3-methyl-2-buten-1-yl)-8-bromo-xanthine Rf value: 0.58 (silica gel, petroleum ether/ethyl acetate/methanol =
6:3.5:0.5) Mass spectrum (ESI+): m/z = 352, 354 [M+H]+

(37) 1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylami no)-piperidin-l-yl]-xanthine Rf value: 0.30 (silica gel, petroleum ether/ethyl acetate/methanol =
7:2.5:0.5) Mass spectrum (ESI+): m/z = 551 [M+H]+

(38) 1-[2-(2-methoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Mass spectrum (ESI+): m/z = 581 [M+H]+

(39) 1-[2-(thiophen-3-yl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-l -yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-l-yl]-xanthine Mass spectrum (ESI+): m/z = 557 [M+H]+

(40) 1-[2-(4-methoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Mass spectrum (ESI+): m/z = 581 [M+H]+

(41) 1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[(S)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine (42) 1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Mass spectrum (ESI+): m/z = 551 [M+H]+

(43) 1-(phenylsulphanylmethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine At value: 0.30 (silica gel, petroleum ether/ethyl acetate/methanol = 7:2:1) Mass spectrum (ESI+): m/z = 555 [M+H]+

(44) 1-[2-(3-methoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Rf value: 0.30 (silica gel, petroleum ether/ethyl acetate/methanol = 7:2:1) (45) 1-[2-(4-methyl-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidi n-1-yl]-xanthine Rf value: 0.20 (silica gel, petroleum ether/ethyl acetate/methanol = 7:2:1) Mass spectrum (ESI+): m/z = 565 [M+H]+

(46) 1-(2-methoxycarbonyl-2-propen-1 -yl)-3-methyl-7-(3-methyl-2-buten- 1 -yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1 -yl]-xanthine Rf value: 0.15 (silica gel, petroleum ether/ethyl acetate/methanol = 75:20:5) Mass spectrum (ESI+): m/z = 531 [M+H]+

(47) 1-(3-oxo-3-phenyl-propyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylami no)-piperidin-1-yl]-xanthine Mass spectrum (ESI+): m/z = 565 [M+H]+

(49) 1-(2-oxo-propyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Rf value: 0.10 (silica gel, petroleum ether/ethyl acetate/methanol = 6:3:1) Mass spectrum (ESI+): m/z = 489 [M+H]+

(50) 1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-(2-cyano-benzyl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Mass spectrum (ESI+): m/z = 598 [M+H]+

(51) 1-(2-phenyl-ethyl)-3-methyl-7-(2-cyano-benzyl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Rf value: 0.50 (silica gel, cyclohexane/ethyl acetate = 1:1) Mass spectrum (ESI+): rn/z = 584 [M+H]+

(52) 1-(3-methoxycarbonyl-2-propen-1-yl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Mass spectrum (ESI+): m/z = 531 [M+H]+

(53) 1-[2-(2,5-dimethoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Rf value: 0.31 (silica gel, cyclohexane/ethyl acetate/methanol = 6:3:1) (54) 1-[2-(4-fluoro-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylami no)-pi peri din- 1 -yl]-xanthine Rf value: 0.40 (silica gel, petroleum ether/ethyl acetate/methanol = 6:3:1) (55) 1-[2-(3-hydroxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-l-yl]-xanthine (By reacting Example 11(18) with 2-bromo-l-[3-(tort.-butyl-dimethyl-silanyloxy)-phenyl]-ethanone in the presence of potassium tert. butoxide in dimethylformamide at ambient temperature) Mass spectrum (ESI+): m/z = 567 [M+H]+

(56) 1-(3-methoxycarbonyl-2-propen-l-yl)-3-methyl-7-(2-cyano-benzyl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Rf value: 0.50 (silica gel, cyclohexane/ethyl acetate = 1:1) Mass spectrum (ESI+): rn/z = 600 [M+Na]+

(57) 1-[(pyridin-2-yl)methyl]-3-methyl-7-(2-cyano-benzyl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-l -yl]-xanthine Mass spectrum (ESI+): rnlz = 571 [M+H]+

(58) 1-(2-phenyl-2-oxo-ethyl)-3-[(methoxycarbonyl)methyl]-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Rf value: 0.68 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 609 [M+H]+

(59) 1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-chloro-xanthine Rf value: 0.55 (silica gel, cyclohexane/ethyl acetate/methanol = 6:3:1) Mass spectrum (ESI+): m/z = 387, 389 [M+H]+

(60) 1-[2-(3-allyloxycarbonylamino-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-l-yl]-xanthine Rf value: 0.40 (silica gel, cyclohexane/ethyl acetate/methanol = 6:3:1) Mass spectrum (ESI+): m/z = 650 [M+H]+

(61) 1-[2-(3-nitro-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-l -yl)-8-chloro-xanthine Mass spectrum (ESI+): m/z = 432, 434 [M+H]+

(62) 1-[2-(2-bromo-5-dimethylamino-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine (63) 1-[(thiazol-2-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Rf value: 0.34 (silica gel, methylene chloride/methanol = 95:5) Mass spectrum (ESI+): m/z = 530 [M+H]+

(64) 1-[(benzo[d]isothiazol-3-yl)methyl]-3-methyl-7-(3-methyl-2-buten-l -yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Rf value: 0.40 (silica gel, cyclohexane/ethyl acetate = 1:1) Mass spectrum (ESI+): m/z = 580 [M+H]+

(65) 1-[(isoxazol-3-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Rf value: 0.20 (silica gel, ethyl acetate) Mass spectrum (ESI+): m/z = 514 [M+H]+
(66) 1-[(1-naphthyl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Rf value: 0.41 (silica gel, cyclohexane/ethyl acetate = 1:1) Mass spectrum (ESI+): m/z = 595 [M+Na]+
(67) 1-[(benzo[d]isoxazoi-3-yl)methyl]-3-methyl-7-(3-methyl-2-buten-l -yl)-8-[3-(tert.-butyloxycarbonylami no)-piperidin-1-yl]-xanthine Rf value: 0.60 (silica gel, methylene chloride/methanol = 95:5) Mass spectrum (ESI+): m/z = 564 [M+H]+
(68) 1-cyanomethyl-3-methyl-7-(2-cyano-benzyl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1 -yl]-xanthine Rf value: 0.40 (silica gel, cyclohexane/ethyl acetate = 1:1) Mass spectrum (ESI+): m/z = 541 [M+Na]+
(69) 1-[2-(2-nitro-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-chloro-xanthine Rf value: 0.25 (silica gel, cyclohexane/ethyl acetate/methanol = 7:2:1) Mass spectrum (ESI+): m/z = 432, 434 [M+H]+
(70) 1-[(6-methyl-pyridin-2-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Carried out in the presence of sodium iodide.
Rf value: 0.47 (silica gel, ethyl acetate) Mass spectrum (ESI+): m/z = 538 [M+H]+
(71) 1-cyanomethyl-3-methyl-7-(2-cyano-benzyl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Rf value: 0.40 (silica gel, cyclohexane/ethyl acetate = 1:1) (72) 1-[2-(2-methoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-l -yl)-chloro-xanthine Mass spectrum (ESI+): m/z = 417, 419 [M+H]+
(73) 1-methyl-3-(2-trimethylsilanyl-ethoxymethyl)-7-(2-cyano-benzyl)-xanthine Mass spectrum (ESI+): rn/z = 412 [M+H]+
(74) 1-[(3-methyl-pyridin-2-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Rf value: 0.27 (silica gel, ethyl acetate) Mass spectrum (ESI+): m/z = 538 [M+H]+
(75) 1-[(5-methyl-pyridin-2-yl)methyl]-3-methyl-7-(3-methyl-2-buten-l-yl)-8-[3-(tert.-butyloxycarbonylami no)-piperidin-1-yl]-xanthine Rf value: 0.45 (silica gel, ethyl acetate) Mass spectrum (ESI+): m/z = 538 [M+H]+
(76) 1-[(4-methyl-pyridin-2-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine At value: 0.26 (silica gel, ethyl acetate) Mass spectrum (ESI+): m/z = 538 [M+H]+
(77) 1-[(5-nitro-isoquinolin-1-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylami no)-piperidin-1-yl]-xanthine Rf value: 0.54 (silica gel, methylene chloride/methanol = 95:5) (78) 1-[(2-oxo-1,2-dihydro-quinolin-4-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-l-yi]-xanthine Rf value: 0.38 (silica gel, methylene chloride/methanol = 95:5) Mass spectrum (ESI+): m/z = 590 [M+H]+
(79) 1-[2-(3-cyano-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-l -yl)-8-chloro-xanthine Rf value: 0.52 (silica gel, cyclohexane/ethyl acetate = 1:1) Mass spectrum (ESI+): m/z = 434, 436 [M+Na]+
(80) 1-[2-(3-aminosulphonyl-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-chloro-xanthine Rf value: 0.25 (silica gel, cyclohexane/ethyl acetate = 1:1) Mass spectrum (ESI+): m/z = 466, 468 [M+H]+
(81) 1-[2-(3-aminocarbonyl-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-chloro-xanthine At value: 0.10 (silica gel, cyclohexane/ethyl acetate = 1:1) Mass spectrum (ESI+): m/z = 430, 432 [M+H]+
(82) 1-(2-phenoxy-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxy-carbonylamino)-piperidin-1-yl]-xanthine Rf value: 0.75 (silica gel, cyclohexane/ethyl acetate = 1:4) Mass spectrum (ESI+): m/z = 553 [M+H]+

Example X
1-benzyl-3-(tert.-butyloxycarbonylamino)-4-methyl-piperidine Prepared by catalytic hydrogenation of 1-benzyl-3-(tert.-butyloxycarbonylamino)-4-methyl-pyridinium-bromide in methanol in the presence of platinum dioxide under a hydrogen pressure of 4 bar.

Mass spectrum (El): rr'z = 304 [M]+

Example XI
1-benzvl-3-(tert.-butyloxycarbonylamino)-4-methyl-Dvridinium-bromide Prepared by reacting 3-(tart.-butyloxycarbonylamino)-4-methyl-pyridine with benzyl bromide in toluene Melting point: 200-201 C
Example XII
1-[2-(2,4,6-trimethyl-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-bromo-xanthine Prepared by reacting 3-methyl-7-(3-methyl-2-buten-1-yl)-8-bromo-xanthine with 2-(2,4,6-trimethyl-phenyl)-ethanol in the presence of triphenyiphosphine and diisopropylazodicarboxylate in tetrahydrofuran at ambient temperature Rf value: 0.40 (silica gel, methylene chloride/ethyl acetate = 15:1) Mass spectrum (ESI+): rn/z = 459, 461 [M+H]+

The following compounds are obtained analogously to Example XII:

(1) 1-[2-(2,4-dichloro-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-bromo-xanthine Rf value: 0.40 (silica gel, methylene chloride/ethyl acetate = 15:1) Mass spectrum (El): m/z = 484, 486, 488 [M]+

(2) 1-[2-(thiophen-2-yl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-bromo-xanthine Rf value: 0.50 (silica gel, methylene chloride/ethyl acetate = 15:1) Mass spectrum (El): m/z = 422, 424 [M]+

(3) 1-[2-(thiophen-3-yl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-bromo-xanthine Melting point: 173.8-174.5 C
Mass spectrum (ESI'): m/z = 445, 447 [M+Na]+

(4) 1-[2-(4-tert.-butyl-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yi)-8-bromo-xanthine Rf value: 0.85 (silica gel, methylene chloride/methanol = 30:1) Mass spectrum (ESI+): m/z = 473, 475 [M+H]+

(5) 1-[2-(4-fluoro-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-bromo-xanthine Rf value: 0.70 (silica gel, methylene chloride/ethyl acetate = 15:1) (6) 1-[2-(4-methoxy-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-bromo-xanthine Rf value: 0.70 (silica gel, methylene chloride/ethyl acetate = 15:1) (7) 1-[2-(2-fluoro-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-chloro-xanthine Rf value: 0.75 (silica gel, methylene chloride/ethyl acetate = 20:1) Mass spectrum (ESI+): m/z = 391, 393 [M+H]+

(8) 1-[2-(2-methyl-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-chloro-xanthine Rf value: 0.60 (silica gel, methylene chloride/ethyl acetate = 20:1) Mass spectrum (ESI+): m/z = 387, 389 [M+H]+

(9) 1-[2-(3-methyl-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-chloro-xanthine Rf value: 0.80 (silica gel, methylene chloride/ethyl acetate = 20:1) Mass spectrum (El): m/z = 386, 388 [M]+

(10) 1-[2-(1-naphthyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yi)-8-chloro-xanthine Rf value: 0.70 (silica gel, methylene chloride/ethyl acetate = 20:1) Mass spectrum (ESI+): m/z = 423, 425 [M+H]+

(11) 1-[2-(2-naphthyl)-ethyl]-3-methyl-7-(3-methyl-2-buten- 1 -yl)-8-chloro-xanthine Rf value: 0.72 (silica gel, methylene chloride/ethyl acetate = 20:1) Mass spectrum (ESI+): m/z = 423, 425 [M+H]+

(12) 1-(4-phenyl-butyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-chloro-xanthine Mass spectrum (ESI+): m/z = 401, 403 [M+H]+

(13) 1-[2-(3-trifluoromethyl-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-chloro-xanthine Rf value: 0.55 (silica gel, petroleum ether/ethyl acetate/methanol = 75:20:5) Mass spectrum (ESI+): m/z = 463, 465 [M+Na]+

(14) 1-[2-(pyridin-2-yl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-bromo-xanthine Mass spectrum (ESI+): m/z = 417, 419 [M+H]+

(15) 1-[2-(pyrrol-1-yl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-chloro-xanthine Rf value: 0.40 (silica gel, petroleum ether/ethyl acetate/methanol = 75:20:5) Mass spectrum (ESI+): m/z = 384, 386 [M+Na]+

(16) 1-[2-([1,2,3]triazol-1-yl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-chloro-xanthine Rf value: 0.22 (silica gel, petroleum ether/ethyl acetate/methanol = 7:2:1) Mass spectrum (ESI+): rr/z = 364, 366 [M+H]+

(17) 1-[2-(pyridin-4-yl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-chloro-xanthine Rf value: 0.15 (silica gel, petroleum ether/ethyl acetate/methanol = 7:2:1) Mass spectrum (ESI+): m/z = 374, 376 [M+H]+

(18) 1-(3-butyn-1-yl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-bromo-xanthine Rf value: 0.45 (silica gel, petroleum ether/ethyl acetate = 7:3) Mass spectrum (ESI+): m/z = 387, 389 [M+Na]+

(19) 1-(3-butene- 1 -yl)-3-methyl-7-(3-methyl-2-buten- 1 -yl)-8-bromo-xanthi ne Rf value: 0.45 (silica gel, petroleum ether/ethyl acetate = 7:3) Mass spectrum (ESI+): m/z = 389, 391 [M+Na]+

(20) 1-(4-pentyn-1-yl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-chloro-xanthine Rf value: 0.37 (silica gel, petroleum ether/ethyl acetate/methanol = 80:15:5) Mass spectrum (El): m/z = 378, 380 [M]+

(21) 1-(4-penten-1-yl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-bromo-xanthine Rf value: 0.30 (silica gel, petroleum ether/ethyl acetate = 8:2) Mass spectrum (ESI+): m/z = 381, 383 [M+H]+

(22) 1-{2-[4-(tert.-butyl-dimethyl-silanyloxy)-phenyl]-ethyl}-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[(S)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Rf value: 0.68 (silica gel, cyclohexane/ethyl acetate = 3:1) Mass spectrum (ESI+): m/z = 667 [M+H]+

(23) 1-{2-[3-(tert.-butyl-dimethyl-silanyloxy)-phenyl]-ethyl}-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[(S)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Rf value: 0.60 (silica gel, cyclohexane/ethyl acetate = 1:1) Mass spectrum (ESI+): m/z = 667 [M+H]+

,,. (24) 1-[2-(pyridin-3-yl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-bromo-xanthine Rf value: 0.17 (silica gel, petroleum ether/ethyl acetate/methanoVconc.
aqueous ammonia = 7:2:1:0.1) Mass spectrum (ESI+): m/z = 418, 420 [M+H]+

(25) 1-[2-(4-methyl-thiazol-5-yl)-ethyl]-3-methyl-7-(3-methyl-2-buten-l -yl)-8-bromo-xanthine Rf value: 0.55 (silica gel, petroleum ether/ethyl acetate/methanol = 5:4:1) Mass spectrum (ESI+): m/z = 438, 440 [M+H]+

(26) 1-[2-(3-methoxy-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-bromo-xanthine Rf value: 0.60 (silica gel, petroleum ether/ethyl acetate/methanol =
7:2.5:0.5) Mass spectrum (ESI+): nVz = 447, 449 [M+H]+

(27) 1-[2-(3-bromo-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-bromo-xanthine Rf value: 0.60 (silica gel, petroleum ether/ethyl acetate/methanol =
7:2.5:0.5) Mass spectrum (El): m/z = 494, 496, 498 [M]+

-yl)-8-bromo-(28) 1-[2-(3-chloro-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-bromo-xanthine Rf value: 0.60 (silica gel, petroleum ether/ethyl acetate/methanol =
7:2.5:0.5) Mass spectrum (El): m/z = 450, 452, 454 [M]+

(29) 1-[2-(2-chloro-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-chloro-xanthine Rf value: 0.65 (silica gel, petroleum ether/ethyl acetate/methanol =
7:2.5:0.5) Mass spectrum (ESI+): m/z = 407, 409, 411 [M+H]+

(30) 1-[2-(2-methoxy-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-chloro-xanthine Rf value: 0.65 (silica gel, petroleum ether/ethyl acetate/methanol =
7:2.5:0.5) Mass spectrum (ESI+): m/z = 403, 405 [M+H]+

(31) 1-[2-(2-trifluoromethyl-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-bromo-xanthine Rf value: 0.55 (silica gel, petroleum ether/ethyl acetate = 8:2) Mass spectrum (ESI+): m/z = 485, 487 [M+H]+

(32) 1-[2-(2-bromo-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-chloro-xanthine Rf value: 0.55 (silica gel, petroleum ether/ethyl acetate = 8:2) Mass spectrum (ESI+): m/z = 451, 453, 455 [M+H]+

(33) 1-[2-(3-fluoro-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-chloro-xanthine Rf value: 0.60 (silica gel, petroleum ether/ethyl acetate = 8:2) Mass spectrum (ESI+): m/z = 391, 393 [M+H]+

(34) 1-[2-(3-nitro-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-chloro-xanthine Rf value: 0.45 (silica gel, petroleum ether/ethyl acetate/methanol = 7:2:1) Mass spectrum (ESI+): m/z = 440, 442 [M+Na]+

(35) 1-[2-(4-methyl-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-chloro-xanthine Rf value: 0.50 (silica gel, petroleum ether/ethyl acetate/methanol = 7:2:1) Mass spectrum (ESI+): m/z = 387, 389 [M+H]+

(36) 1-[2-(2-nitro-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-chloro-xanthine Rf value: 0.85 (silica gel, petroleum ether/ethyl acetate/methanol = 6:3:1) Mass spectrum (ESI+): m/z = 418, 420 [M+H]+

(37) 1-[2-(3,5-difluoro-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-chloro-xanthine Rf value: 0.50 (silica gel, petroleum ether/ethyl acetate = 7:3) Mass spectrum (El): m/z = 408, 410 [M]+

(38) 1-[2-(2,6-difluoro-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yi)-8-chloro-xanthine At value: 0.50 (silica gel, petroleum ether/ethyl acetate = 7:3) Mass spectrum (ESI+): m/z = 409, 411 [M+H]+

(39) 1-[2-(3,5-dimethyl-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-l -yl)-8-chloro-xanthine Rf value: 0.58 (silica gel, petroleum ether/ethyl acetate = 7:3) Mass spectrum (ESI+): n-Vz = 401, 403 [M+H]+

(40) 1-(2-phenyl-propyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-chloro-xanthine Rf value: 0.60 (silica gel, petroleum ether/ethyl acetate/methanol = 7:2:1) Mass spectrum (ESI+): m/z = 387, 389 [M+H]+

(41) 1-(2-methoxy-2-phenyl-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-chloro-xanthine Rf value: 0.70 (silica gel, petroleum ether/ethyl acetate/methanol = 7:2:1) Mass spectrum (ESI+): rn/z = 425, 427 [M+Na]+

(42) 1-[(pyridin-2-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-chloro-xanthine Rf value: 0.14 (silica gel, petroleum ether/ethyl acetate = 1:1) Mass spectrum (ESI+): n-Vz = 360, 362 [M+H]+

(43) 1-[(isoquinolin-1-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-chloro-xanthine At value: 0.31 (silica gel, cyclohexane/ethyl acetate = 1:1) Mass spectrum (ESI+): n-Vz = 410, 412 [M+H]+

(44) 1-[(pyridin-3-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-chloro-xanthine _ Rf value: 0.10 (silica gel, methylene chloride/methanol = 98:2) Mass spectrum (ESI+): rn/z = 360, 362 [M+H]+

(45) 1-[(pyridin-4-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-chloro-xanthine Rf value: 0.24 (silica gel, methylene chloride/methanol = 95:2) Mass spectrum (ESI+): n-Vz = 360, 362 [M+H]+

(46) 1-[(isoquinolin-4-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-chloro-xanthine Rf value: 0.28 (silica gel, ethyl acetate/petroleum ether = 2:1) Mass spectrum (ESI+): m/z = 410, 412 [M+H]+

(47) 1-[(1-methyl-1 H-indazol-3-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-chloro-xanthine Mass spectrum (ESI+): m/z = 413, 415 [M+H]+

(48) 1-[(quinolin-4-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-chloro-xanthine Rf value: 0.39 (silica gel, ethyl acetate) Mass spectrum (ESI+): m/z = 410, 412 [M+H]+

(49) 1-[(quinolin-8-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-chloro-xanthine Rf value: 0.74 (silica gel, ethyl acetate) Mass spectrum (ESI+): rn/z = 410, 412 [M+H]+
Example XIII
1,3-dimethyl-5-[trans-2-(tert.-butyloxycarbonylamino)-cyclohexyl]-carbonylamino}-6-amino-uracil Prepared by treating 1,3-dimethyl-5-({trans-2-[(fluoren-9-ylmethoxycarbonyl)amino]-cyclohexyl}-carbonylami no)-6-amino-uracil with piperidine in dimethylformamide and subsequently reacting with di-tert.butyl pyrocarbonate Mass spectrum (ESI+): m/z = 396 [M+H]+
Example XIV
1-methyl-3-(2-gropen-1-yl}-7-benzyl-8-chloro-xanthine Prepared by reacting 1-methyl-7-benzyl-8-chloro-xanthine with propargyl bromide in the presence of potassium carbonate in dimethylformamide at ambient temperature Melting point: 169-172 C
Mass spectrum (El): m/z = 328, 330 [M]+

The following compounds are obtained analogously to Example XIV:
(1) 1-methyl-3-(2-propen-1-yl)-7-benzyl-8-chloro-xanthine Rf value: 0.83 (silica gel, methylene chloride/methanol = 95:5) Mass spectrum (El): m/z = 330, 332 [M]+

(2) 1-methyl-3-(2-phenyl-ethyl)-7-benzyl-8-chloro-xanthine Melting point: 174-179 C
Mass spectrum (ESI+): m/z = 395, 397 [M+H]+

(3) 1-phenyl-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[(3-(tert.-butyloxycarbonylamino)-pi peridi n-1-yl]-xanthine Rf value: 0.66 (aluminium oxide, ethyl acetate/petroleum ether = 8:2) Mass spectrum (ESI+): m/z = 509 [M+H]+

(4) 1-methyl-3-(2-dimethylamino-ethyl)-7-benzyl-8-chloro-xanthine At value: 0.30 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
9:1:0.1) Mass spectrum (ESI+): rn/z = 362, 364 [M+H]+

(5) 1,3-bis(2-phenyl-ethyl)-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Rf value: 0.79 (silica gel, petroleum ether/ethyl acetate = 4:6) Mass spectrum (ESI+): m/z = 627 [M+H]+

(6) 1-(2-phenyl-ethyl)-3-cyanomethyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine At value: 0.74 (silica gel, ethyl acetate/petroleum ether = 6:4) Mass spectrum (ESI+): m/z = 562 [M+H]+

(7) 1-(2-phenyl-ethyl)-3-[(methoxycarbonyl)-methyl]-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Rf value: 0.65 (silica gel, ethyl acetate/petroleum ether = 6:4) Mass spectrum (ESI+): m/z = 595 [M+H]+

(8) 1-(2-phenyl-ethyl)-3-(2-dimethylamino-ethyl)-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Rf value: 0.39 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI'): m/z = 594 [M+H]+

(9) 1-(2-phenyl-ethyl)-3-(2-propyn-1-yl)-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Rf value: 0.77 (silica gel, ethyl acetate/petroleum ether = 6:4) Mass spectrum (ESI+): m/z = 561 [M+H]+

(10) 1-methyl-3-(2-phenyl-2-oxo-ethyl)-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Rf value: 0.69 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
95:5:1) Mass spectrum (ESI+): rr/z = 551 [M+H]+

(11) 1 -methyl-3-cyanomethyl-7-(3-methyl-2-buten-1 -yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1 -yl]-xanthine Rf value: 0.80 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 472 [M+H]+

(12) 1-methyl-3-(2-phenyl-ethyl)-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Rf value: 0.88 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): rn/z = 537 [M+H]+

(13) 1-methyl-3-(2-dimethylamino-ethyl)-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Rf value: 0.21 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 504 [M+H]+

(14) 1-methyl-3-isopropyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Rf value: 0.54 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
95:5:1) (15) 1-methyl-3-(2-cyano-ethyl)-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Rf value: 0.59 (silica gel, methylene chioride/methanol/conc. aqueous ammonia =
90:10:1) (16) 1-methyl-3-[2-(4-methoxy-phenyl)-ethyl]-7-(3-methyl-2-buten-1-yi)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Rf value: 0.88 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 567 [M+H]+

(17) 1-methyl-3-[2-(3-methoxy-phenyl)-ethyl]-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Rf value: 0.76 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 567 [M+H]+

(18) 1-methyl-3-[2-(2-methoxy-phenyl)-ethyl]-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yi]-xanthine Rf value: 0.68 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) (19) 1-methyl-3-[2-(3-methyl-phenyl)-ethyl]-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylami no)-piperidin-1-yl]-xanthine Rf value: 0.81 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): rn/z = 551 [M+H]+

(20) 1-methyl-3-[2-(4-methyl-phenyl)-ethyl]-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Rf value: 0.81 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 551 [M+H]+

(21) 1-methyl-3-[2-(2-methyl-phenyl)-ethyl]-7-(3-methyl-2-buten-1-yi)-8-[3-(tert.-butyloxycarbonylami no) -pipe ridi n-1 -yl]-xanthine Rf value: 0.72 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) (22) 1-methyl-3-[2-(2-fluoro-phenyl)-ethyl]-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Rf value: 0.89 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 555 [M+H]+

(23) 1-methyl-3-(4-phenyl-butyl)-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylami no)-piperidin-1-yl]-xanthine Rf value: 0.65 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 565 [M+H]+

(24) 1-methyl-3-(3-phenyl-propyl)-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Rf value: 0.84 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 551 [M+H]+

(25) 1-methyl-3-[2-(4-fluoro-phenyl)-ethyl]-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Rf value: 0.80 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
98:2:1) Mass spectrum (ESI+): m/z = 555 [M+H]+

(26) 1-methyl-3-[2-(3-fluoro-phenyl)-ethyl]-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Rf value: 0.82 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 555 [M+H]+

(27) 1-methyl-3-(2-phenyl-ethyl)-7-(2-cyano-benzyl)-8-chloro-xanthine Mass spectrum (ESI+): m/z = 420, 422 [M+H]+

Example XV
1-methyl-7-benzyl-8-chloro-xanthine Prepared by treating 1-methyl-3-(2-trimethylsilanyl-ethoxymethyl)-7-benzyl-8-chloro-xanthine with trifluoroacetic acid in methylene chloride at ambient temperature Rf value: 0.10 (silica gel, methylene chloride/methanol = 98:2) The following compound is obtained analogously to Example XV:
1) 1-methyl-7-(2-cyano-benzyl)-8-chloro-xanthine Mass spectrum (ESI+): m/z = 338, 340 [M+Na]+

Example XVI
1 3-di methyl-7-(3-methyl-phenyl)-8-chloro-xanthine Prepared by reacting 8-chloro-theophylline with 3-methylphenylboric acid in the presence of anhydrous copper(li)acetate, pyridine and molecular sieve 4A in methylene chloride at ambient temperature Mass spectrum (ESI+): m/z = 305, 307 [M+H]+

The following compounds are obtained analogously to Example XVI:
(1) 1,3-dimethyl-7-((E)-1-hexen-1-yl)-8-chloro-xanthine Mass spectrum (ESI+): m/z = 297, 299 [M+H]+

(2) 1,3-dimethyl-7-((E)-2-phenyl-vinyl)-8-chloro-xanthine Mass spectrum (ESI'): m/z = 317, 319 [M+H]+

(3) 1,3-dimethyl-7-(2-naphthyl)-8-chloro-xanthine Rf value: 0.60 (silica gel, cyclohexane/ethyl acetate = 1:1) Mass spectrum (ESI+): m/z = 341, 343 [M+H]+

(4) 1,3-dimethyl-7-phenyl-8-chloro-xanthine Rf value: 0.60 (silica gel, cyclohexane/ethyl acetate = 1:1) Mass spectrum (ESI+): m/z = 291, 293 [M+H]+

(5) 1,3-dimethyl-7-(3,5-dimethyl-phenyl)-8-chloro-xanthine Rf value: 0.60 (silica gel, cyclohexane/ethyl acetate = 1:1) Mass spectrum (ESI+): m/z =.319, 321 [M+H]+

(6) 1,3-dimethyl-7-(4-methyl-phenyl)-8-chloro-xanthine Rf value: 0.60 (silica gel, cyclohexane/ethyl acetate = 1:1) Mass spectrum (ESI+): m/z = 305, 307 [M+H]+

(7) 1,3-dimethyl-7-(3-trifluoromethyl-phenyl)-8-chloro-xanthine Rf value: 0.60 (silica gel, cyclohexane/ethyl acetate = 1:1) Mass spectrum (ESI+): m/z = 381, 383 [M+Na]+

(8) 1,3-dimethyl-7-(3-cyano-phenyl)-8-chloro-xanthine Rf value: 0.50 (silica gel, cyclohexane/ethyl acetate = 1:1) Mass spectrum (ESI+): m/z = 338, 340 [M+Na]+

(9) 1,3-dimethyl-7-(3-fluoro-phenyl)-8-chloro-xanthine Rf value: 0.50 (silica gel, cyclohexane/ethyl acetate = 1:1) Mass spectrum (El): rr/z = 308, 310 [M]+

Example XVII
cis-N-methyl-cyclohexane-1.2-diamine Prepared by treating cis-N-(tert.-butyloxycarbonyl)-cyclohexane-1,2-diamine with lithium aluminium hydride in tetrahydrofuran by refluxing Rf value: 0.10 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 129 [M+H]+
Example XVIII
1 -(tert.-butyloxvcarbonyl)-3-metylamino-piperidine Prepared by treating 1-(tert.-butyloxycarbonyl)-3-[N-(2,2,2-trifluoro-acetyl)-N-methyl-amino]-piperidine with 2N sodium hydroxide solution in methanol at ambient temperature Rf value: 0.40 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 215 [M+H]+

The following compounds are obtained analogously to Example XVIII:
(1) 1-(tert.-butyloxycarbonyl)-3-methylamino-pyrrolidine Rf value: 0.42 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): mlz = 201 [M+H]+

(2) 2-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-3-benzyl-4-ethoxycarbonyl-5-methylami no-3 H-i midazol e Carried out with sodiuim ethoxide in ethanol.
Rf value: 0.60 (silica gel, petroleum ether/ethyl acetate = 1:1) Example XIX
1-(tert-butyloxycarbonyl)-3-f N-(2.2.2-trifluoro-acetyl)-N-methyl-aminol-piperidine Prepared by reacting 1-(tert.-butyloxycarbonyl)-3-[(2,2,2-trifluoro-acetyl)amino]-piperidine with sodium hydride and methyl iodide in tetrahydrofuran at ambient temperature Rf value: 0.78 (silica gel, methylene chloride/methanol = 95:5) The following compounds are obtained analogously to Example XIX:

(1) 1-(tert.-butyloxycarbonyl)-3-[N-(2,2,2-trifluoro-acetyl)-N-methyl-amino]-pyrrolidine (2) 2-[3-(tert.-Butyloxycarbonylamino)-piperidin-1-yl]-3-benzyl-4-ethoxycarbonyl-5-[N-(2,2,2-trifluoro-acetyl)-N-methyl-amino]-3H-imidazole Carried out with potassium carbonate in dimethylformamide.
Rf value: 0.60 (silica gel, petroleum ether/ethyl acetate = 1:1) Example XX
1-(tert.-butyloxycarbonyl)-3-1(2,2.2-trifluoro-acetvl)aminol-gipendine Prepared by reacting 3-amino-l-(tert.-butyloxycarbonyl)-piperidine with methyl trifluoroacetate in methanol at ambient temperature Rf value: 0.73 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI"): rriz = 295 [M-H]"

The following compound is obtained analogously to Example XX:

(1) 2-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-3-benzyl-4-ethoxycarbonyl-5-[(2,2,2-trifl uoro-acetyl)ami no]-3H-i midazole Carried out with trifluoroacetic anhydride in the presence of 4-dimethylamino-pyridine in methylene chloride at ambient temperature.
Rf value: 0.70 (silica gel, petroleum ether/ethyl acetate = 1:1) ell, Example XXI
(S)-2-amino-1-methylamino-12ropane-di hydrochloride Prepared by refluxing (S)-alanine-methylamide-hydrochloride with lithium aluminium hydride in tetrahydrofuran and precipitating the product obtained after working up in the form of the dihydrochloride Rf value: 0.08 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI"): m/z = 159, 161, 163 [M+HCI+Cl]"

The following compound is obtained analogously to Example XXI:
(1) (R)-2-amino-l -methylamino-propane-di hydrochloride Mass spectrum (El): m/z = 88 [M]+
Example XXII
1-phenyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Prepared by refluxing 2-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-3-(3-methyl-2-buten-1-yl)-4-ethoxycarbonyl-5-[(phenylaminocarbonyl)amino]-3H-imidazole with potassium tert. butoxide in ethanol Rf value: 0.75 (aluminium oxide, methylene chloride/methanol/conc. aqueous ammonia = 9:1:0.1) Mass spectrum (ESI+): m/z = 495 [M+H]+

The following compounds are obtained analogously to Example XXII:

(1) 1-(2-phenyl-ethyl)-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Rf value: 0.71 (silica gel, ethyl acetate) Mass spectrum (ESI+): m/z = 523 [M+H]+

O 2 1-methY1-7-(3-methy1-2-buten-1-y1)-8-[3-(tert.-butYtoxYcarbonYlamino)-PiPeridin-l-yl]-xanthine Carried out with sodium ethoxide in ethanol at ambient temperature Melting point: 182-185 C
Mass spectrum (ESI+): m/z = 433 [M+H]+

(3) 1-amino-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-l-yl]-xanthine (Contaminated with 1-amino-7-(3-methyl-butyl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine) Carried out with sodium ethoxide in ethanol at ambient temperature Rf value: 0.26 (silica gel, methylene chioride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 434 [M+H]+

(4) 7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Rf value: 0.24 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 419 [M+H]+

(5) potassium-{3-methyl-7-benzyl-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine}-2-thiolate Carried out in n-butanol at 105 C.
Rf value: 0.90 (aluminium oxide, methylene chloride/methanol =10:1) Example XXIII
2-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-3-(3-methyl-2-buten-1-yl)-4-ethoxycarbonvl-5-f(phenyl-aminocarbonyflaminol-3H-imidazol Prepared by refluxing 2-[3-(te rt.-butyloxycarbonyl ami no)-pi pe rid in- 1-yl]-3-(3-methyl-2-buten-1 -yl)-4-ethoxycarbonyl-5-amino-3H-imidazole with phenylisocyanate in 1,2-dimethoxyethane ?OPIN Mass spectrum (ESI+): m/z = 541 [M+H]+

The following compounds are obtained analogously to Example XXIII:

(1) 2-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-3-(3-methyl-2-buten-1-yl)-4-ethoxycarbonyl-5-{[(2-phenyl-ethyl)-ami nocarbonyl]ami no}-3 H-i midazole Rf value: 0.70 (silica gel, ethyl acetate) Mass spectrum (ESI+): rn/z = 569 [M+H]+

(2) 2-[3-(tert.-butyl oxycarbonylami no)-pi peri din- 1 -yl]-3-(3-methyl-2-buten-1 -yl)-4-ethoxycarbonyl-5-[(methyl-aminocarbonyl)amino]-3H-imidazole eft, Carried out at 130 C in a Roth bomb Mass spectrum (ESI+): m/z = 479 [M+H]+

(3) 2-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-3-(3-methyl-2-buten-1-yl)-4-ethoxycarbonyl-5-{[(ethoxycarbonylamino)carbonyl]amino}-3H-imidazole Rf value: 0.29 (silica gel, methylene chloride/methanol/conc. aqueous ammonia 90:10:1) Mass spectrum (ESI+): m/z = 537 [M+H]+

(4) 1-[2-(3-{[(ethoxycarbonylamino)carbonyl]amino}-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Carried out in the presence of triethylamine in a mixture of methylene chloride and dimethylformamide at ambient temperature.
Rf value: 0.41 (silica gel, cyclohexane/ethyl acetate = 1:2) (5) 2-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-3-benzyl-4-ethoxycarbonyl-5-{N-[(ethoxycarbonylamino)thiocarbonyl]-N-methyl-ami no}-3H-imidazole Carried out by refluxing with ethoxycarbonylisothiocyanate in tetrahydrofuran.
Rf value: 0.35 (silica gel, petroleum ether/ethyl acetate = 1:1) Example XXIV
2-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-3-(3-methyl-2-buten-1-yl)-4-ethoxycarbonyi-5-amino-3H-i midazole Prepared by reacting cyanimino-[N-(3-methyl-2-buten-1 -yl)-N-(ethoxycarbonylmethyl)-amino]-[3-(tert.-butyloxycarbonylamino)-piperidin-1 -yl]-methane with sodium in ethanol by refluxing Rf value: 0.26 (aluminium oxide, ethyl acetate/petroleum ether = 8:2) Mass spectrum (ESI+): m/z = 422 [M+H]+

The following compound is obtained analogously to Example XXIV:

-(1) 2-[3-(tert.-butYtoxYcarbonYlamino)-PiPeridin-1-Y1]-3-benty1-4-ethoxycarbony1-5 amino-3H-imidazole Rf value: 0.40 (silica gel, ethyl acetate/petroleum ether = 4:1) Example XXV
Cyanoimino-[N-(3-methyl-2-buten-1-yi)-N-(ethoxycarbonylmethyl)-amino]-[3-(tert.-butyloxycarbonvlamino)-pigeridin-1-yll-methane Prepared by reacting cyanoimino-[(ethoxycarbonylmethyl)amino]-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-methane with 1 -bromo-3-methyl-2-butene in the presence of potassium carbonate in acetone at ambient temperature Mass spectrum (ESI+): m/z = 422 [M+H]+

The following compound is obtained analogously to Example XXV:

(1) cyanoimino-[N-benzyl-N-(ethoxycarbonylmethyl)-amino]-[3-(tert.-butyloxy-carbonylamino)-pipendin-1-yl]-methane Carried out with ethyl bromoacetate in the presence of potassium carbonate in dimethylformamide.
Rf value: 0.70 (silica gel, ethyl acetate/petroleum ether = 4:1) Example XXVI
Cyanoimino-[(ethoxycarbonyl methyl)amino]-[3-(tert.-butyloxycarbonylamino)-pigeridin-1-yl]-methane Prepared by reacting cyanoimino-[(ethoxycarbonylmethyl)amino]-phenyloxy-methane with 3-(tert.-butyloxycarbonylamino)-piperidine in isopropanol at 70 C
Rf value: 0.45 (aluminium oxide, ethyl acetate) Mass spectrum (ESI+): m/z = 354 [M+H]+

The following compound is obtained analogously to Example XXVI:

(1) cyanoimino-benzylamino-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-methane Carried out in dimethylformamide at 80 C.
Rf value: 0.56 (aluminium oxide, methylene chloride/methanol = 40:1) Example XXVII
Cyanoimino-f(ethoxycarbonvlmethvl)amino]-phenyloxy-methane Prepared by reacting diphenylcyanocarbonimidate with ethyl aminoacetate-hydrochloride in the presence of triethylamine in isopropanol at ambient temperature (analogously to R. Besse et al., Tetrahedron 1990, 46, 7803-7812) Mass spectrum (ESI+): m/z = 248 [M+H]+

The following compound is obtained analogously to Example XXVII:

(1) cyanoimino-benzylamino-phenyloxy-methane Rf value: 0.20 (silica gel, petroleum ether/ethyl acetate = 3:1) Mass spectrum (ESI+): m/z = 252 [M+H]+

Example XXVIII
1-((E)-2-phenyl-vinyl)-3-methyl-7-(3-methyl-2-buten-1-vl)-8-bromo-xanthine Prepared by reacting 3-methyl-7-(3-methyl-2-buten-1-yi)-8-bromo-xanthine with (E)-2-phenyl-vinyl-boric acid in the presence of anhydrous copper(ll)acetate and pyridine in methylene chloride at ambient temperature.
Rf value: 0.70 (silica gel, petroleum ether/ethyl acetate/methanol = 6:3:1) Mass spectrum (ESI+): m/z = 415, 417 [M+H]+

Example XXIX
1 3-dimethyl-7-((E)-2-hexen-1-Y)-8-chloro-xanthine Prepared by reacting 8-chloro-theophylline with (E)-2-hexen-1 -ol in the presence of triphenylphosphine and diisopropyl azodicarboxylate in tetrahydrofuran at ambient temperature.
Mass spectrum (El): m/z = 296, 298 [M]+
Example XXX
1-(phenylsulphinylmethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butvloxycarbonylamino)-piperidin-1-yll-xanthine Prepared by oxidation of 1-(phenylsulphanylmethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine with hydrogen peroxide in hexafluoroisopropanol Rf value: 0.40 (silica gel, petroleum ether/ethyl acetate/methanol =
6.5:2:1.5) Mass spectrum (ESI+): m/z = 571 [M+H]+

Example XXXI
1 3-dimethyl-7-(3-methyl-2-buten-1- Iy)-8-(1-nitroso-Dil2eridin-4-vl)-xanthine Prepared by treating 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-(piperidin-4-yl)-xanthine with isoamyl nitrite in tetrahydrofuran at 60 C.
The crude product is immediately reacted further (see Example 8).

(1) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-(1-nitroso-piperidin-3-yl)-xanthine Mass spectrum (ESI+): rn/z = 361 [M+H]+

Example XXXII
1 3-dimethyl-7-((E)-1-buten-1-yl)-8-chloro-xanthine Prepared by refluxing 1,3-dimethyl-7-(2-methanesulphonyloxy-butyl)-8-chloro-xanthine with 1,8-diazabicyclo[5.4.0]undec-7-ene in dioxan.
Mass spectrum (ESI+): m/z = 269, 271 [M+H]+
Example XXXIII
1 3-dimethyl-7-(2-methanesulphonyloxy-butyl)-8-chloro-xanthine Prepared by reacting 1,3-dimethyl-7-(2-hydroxy-butyl)-8-chloro-xanthine with methanes u I phonic acid chloride in methylene chloride in the presence of triethylamine.
Mass spectrum (ESI+): m/z = 365, 367 [M+H]+

The following compounds are obtained analogously to Example XXXIII:

(1) 1-[2-(3-methanesulphonyloxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Mass spectrum (ESI+): m/z = 645 [M+H]+

(2) 1-(2-{3-[bis(methanesulphonyl)-amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine (3) 1-[2-(3-methanesulphonylamino-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)- 8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Carried out with pyridine as an auxiliary base.
Mass spectrum (ESI+): m/z = 644 [M+H]+

(4) 1-[2-(2-methanesulphonyloxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tart.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Mass spectrum (ESI+): m/z = 645 [M+H]+

(5) 1- 2- 2- bis methanesul hon I amino hen 1 2 oxo-eth 13 meth 17- 3 meth I
2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Carried out in dichloroethane with two equivalents of methanesulphonic acid chloride.
Mass spectrum (ESI+): m/z = 722 [M+H]+

Example XXXIV
1 .3-di methyl-7-(2-hydroxy-butyl)-8-chloro-xanthi ne Prepared by reacting 8-chloro-theophylline with 2-ethyl-oxirane in dimethylformamide in the presence of Hunig base at 65 C.
Mass spectrum (ESI+): m/z = 287, 289 [M+H]+
Example XXXV
1-(2-phenyl-ethyl)-3-vinyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butvloxvcarbonvlamino)-piperidin-1-yll-xanthine 135 mg 1-(2-phenyl-ethyl)-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.
butyloxycarbonylamino)-piperidin-1-yl)-xanthine, 84 ,u1 of vinyltrimethoxysilane, 53 mg of anhydrous copper (II)acetate and 0.53 ml of a 1 M solution of tetrabutyl-ammonium fluoride in tetrahydrofuran are suspended in 5 ml of methylene chloride and combined with 200 mg of molecular sieve 4A. Then 43 ,u1 of pyridine are added and the turquoise reaction mixture is stirred for three days at ambient temperature. It is then diluted with methylene chloride and suction filtered through talc. The filtrate is evaporated down in vacuo and the crude product is purified by chromatography through a silica gel column with cyclohexane/ethyl acetate (8:2 to 1:1) as eluant.

Yield: 32 mg (23 % of theory) Rf value: 0.50 (silica gel, cyclohexane/ethyl acetate = 2:1) Mass spectrum (El): m/z = 548 [M]+

Example XXXVI
1-(2-phenyl-ethyl)-3-((E)-2-phenyl-vinyl)-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-oiperidin-1-yll-xanthine Prepared by reacting 1-(2-phenyl-ethyl)-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine with (E)-2-phenylvinyl-boric acid in methylene chloride in the presence of anhydrous copper(II)acetate, pyridine and molecular sieve 4A at ambient temperature.
Rf value: 0.71 (silica gel, petroleum ether/ethyl acetate = 6:4) Mass spectrum (ESI+): m/z = 625 [M+H]+

The following compounds are obtained analogously to Example XXXVI:

(1) 1-methyl-3-phenyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylami no)-piperidin-1-yl]-xanthine Rf value: 0.86 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
95:5:1) to*, Mass spectrum (ESI+): m/z = 509 [M+H]+

(2) 1-methyl-3-((E)-2-phenyl-vinyl)-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxy-carbonylami no)-piperidin-1-yl]-xanthine Melting point: 201-202.5 C
Mass spectrum (ESI+): rn/z = 535 [M+H]+

Example XXXVII
1-(2-hydroxy-2-phenyl-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butvloxycarbonylamino)-piperidin-1 yl]_xanthine Prepared by treating 1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1 -yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1 -yl]-xanthine with sodium borohydride in methanol at ambient temperature.
Rf value: 0.30 (silica gel, petroleum ether/ethyl acetate/methanol = 60:35: 5) Example XXXVIII
1-phenylcarbonylamino-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-12igeridin-1-yl]-xanthine Prepared by reacting 1-amino-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine (contaminated with 1-amino-7-(3-methyl-butyl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine) with benzoyl chloride in the presence of pyridine in methylene chloride at ambient temperature. The product obtained is contaminated with 1-phenylcarbonylamino-7-(3-methyl-butyl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine.
Rf value: 0.16 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 538 [M+H]+
Example XXXIX
2-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-3-(3-methyl-2-buten-1-yl)-4-ethoxvcarbonyl-5-hydrazinocarbonvlamino-31+imidazole Prepared by reacting 2-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-3-(3-methyl-2-buten-1-yl)-4-ethoxycarbonyl-5-ethoxycarbonylamino-3H-imidazole with hydrazin-hydrate in xylene at 150 C. The product obtained is contaminated with 2-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-3-(3-methyl-butyl)-4-ethoxycarbonyl-5-hydrazinocarbonylamino-3H-i midazole.
Rf value: 0.10 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Example XL
2-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-3-(3-methyl-2-buten-1-yl)-4-ethoxycarbonyl-5-ethoxycarbonyl ami n o-3 H-i mi dazol e Prepared by reacting 2-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-3-(3-methyl-2-buten-1-yl)-4-ethoxycarbonyl-5-amino-3H-imidazole with ethyl chioroformate in the presence of 0.5 N sodium hydroxide solution in methylene chloride at 50 C.
Melting point: 129-131 C
Mass spectrum (ESI+): m/z = 494 [M+H]+
Example XLI
1-[2-(3-allyloxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxvcarbonylamino)piperidin-l-vll-xanthine Prepared by reacting 1-[2-(3-hydroxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine with allyl bromide in the presence of potassium carbonate in dimethylformamide at ambient temperature.
Mass spectrum (ESI+): m/z = 607 [M+H]+

The following compounds are obtained analogously to Example XLI:

(1) 1-{2-oxo-2-[3-(2-propyn-1-yloxy)-phenyl]-ethyl}-3-methyl-7-(3-methyl-2-buten-l -yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Mass spectrum (ESI+): rn/z = 627 [M+Na]+

(2) 1-(2-{3-[(methoxycarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-l-yl]-xanthine Mass spectrum (ESI+): m/z = 639 [M+H]+

(3) 1-[2-(3-cyanomethoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-l-yl]-xanthine Mass spectrum (ESI+): m/z = 606 [M+H]+

(4) 1-[2-(3-benzyloxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-l-yl]-xanthine Mass spectrum (ESI+): rn/z = 657 [M+H]+

(5) 1-[2-(3-phenylsulphonyloxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-l -yi)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Mass spectrum (ESI+): m/z = 707 [M+H]+

(6) 1-(2-{2-[(methoxycarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Mass spectrum (ESI+): m/z = 639 [M+H]+

(7) 1-[2-(2-cyanomethoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-l-yl]-xanthine Mass spectrum (ESI+): rn/z = 606 [M+H]+

(8) 1-(2-{3-[(dimethylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-l-yl]-xanthine Rf value: 0.25 (silica gel, cyclohexane/ethyl acetate/methanol = 5:4:1) Mass spectrum (ESI+): m/z = 652 [M+H]+

(9) 1-(2-{3-[(methylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-l-yl]-xanthine Rf value: 0.24 (silica gel, cyclohexane/ethyl acetate/methanol = 5:4:1) Mass spectrum (ESI+): m/z = 638 [M+H]+

(10) 1-(2-{3-[(aminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Rf value: 0.30 (silica gel, cyclohexane/ethyl acetate/methanol = 5:4:1) Mass spectrum (ESI+): m/z = 624 [M+H]+

Example XLII
1-[2-(3-phenyloxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-12iperidin-1-yll-xanthine Prepared by reacting 1-[2-(3-hydroxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine with phenylboric acid in methylene chloride in the presence of anhydrous copper(II)acetate, pyridine and molecular sieve 4A at ambient temperature.
Mass spectrum (ESI'): m/z = 643 [M+H]+
Example XLIII
1-[2-(3-amino-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butvloxycarbonylamino)_Diperidin-l -yl]-xanthine Prepared by treating 1-[2-(3-allyloxycarbonylamino-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine with tetrakis(triphenyl phosphine)palIadium(0) and 5,5-dimethyl-1,3-cyclohexanedione in tetrahydrofuran at ambient temperature.
Rf value: 0.22 (silica gel, cyclohexane/ethyl acetate/methanol/conc. aqueous ammonia = 60:30:10:1) Example XLIV
1-(3-allyloxycarbonylamino-phenyl)-2-bromo-ethan-1 -on and 1 -(3-allyloxvcarbonvlamino phenyl)-2-chloro-ethan-1-one Prepared by reacting 1-(3-amino-phenyl)-2-bromo-ethan-l-one-hydrobromide with allyl chloroformate in methylene chloride in the presence of Honig base. A
mixture of the chlorine and bromine compounds is obtained.
Rf value: 0.50 (silica gel, cyclohexane/ethyl acetate/methanol = 6:3:1) Mass spectrum (ESI"): rn/z = 252, 254 [M1-H] 296, 298 [M2-H]"

Example XLV
1-[2-(3-amino-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)_piperidin-1-yll-xanthine Prepared by treating 1-[2-(3-nitro-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine with iron filings in a mixture of ethanol, water and glacial acetic acid (80:25:10) at 100 C.
Rf value: 0.55 (silica gel, cyclohexane/ethyl acetate/methanol/conc. aqueous ammonia = 50:30:20:1) Mass spectrum (ESI+): m/z = 566 [M+H]+

The following compounds are obtained analogously to Example XLV:

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

(2) 1-[(5-amino-isoquinolin-1-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Rf value: 0.53 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): rn/z = 589 [M+H]+
Example XLVI
2-bromo-l -(3-dimethylamino-phenyl)-ethan-1-one and 2-bromo-l -(2-bromo-5-dimethylamino-phenyl)-ethan-1-one Prepared by refluxing 1-(3-dimethylamino-phenyl)-ethan-1-one with bromine in the presence of acetic acid in ethyl acetate. A mixture of the mono- and dibromo compounds is obtained.
Mass spectrum (ESI+): m/z = 242, 244 [M1+H]+; 320, 322, 324 [M2+H]+

Example XLVII
1-[2-(3-metoxycarbonylamino-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-y)-8-j3-(tert-butyloxycarbonylamino)-piperidin-1-yll-xanthine Prepared by reacting 1-[2-(3-amino-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine with methyl chloroformate in the presence of triethylamine in a mixture of methylene chloride and dimethylformamide (3:1) at ambient temperature.
Mass spectrum (ESI+): m/z = 624 [M+H]+

The following compound is obtained analogously to Example XLVII:

(1) 1-(2-{3-[(dimethylaminocarbonyl)amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Reaction carried out with dimethylcarbamoylchloride in the presence of potassium carbonate in dimethylformamide at 75 C.
Rf value: 0.30 (silica gel, cyclohexane/ethyl acetate/methanol = 6:4:1) Mass spectrum (El): m/z = 636 [M]+

Example XLVIII
1-[2-(3-acetylamino-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert-butvloxycarbonylamino)-piperidin-1-yl]-xanthine Prepared by reacting 1-[2-(3-amino-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine with acetyl chloride in the presence of pyridine in a mixture of methylene chloride and dimethylformamide (3:1) at ambient temperature.
Mass spectrum (ESI+): m/z = 608 [M+H]+

The following compound is obtained analogously to Example XLVIII:

(1) 1-[2-(2-acetylamino-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Mass spectrum (ESI+): m/z = 608 [M+H]+

Example XLIX
1-[2-(3-cyanomethylamino-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert -butyloxycarbonvlamino)-piperidin-1-yl]-xanthine Prepared by reacting 1-[2-(3-amino-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine with bromoacetonitrile in the presence of Hunig base in dimethylformamide at 70 C.
Rf value: 0.18 (silica gel, cyclohexane/ethyl acetate = 1:2) Example L
1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-{cis-N-[2-(tert.-butyloxycarbonylamino)-c cly ohexyl]-N-methyl-amino}-xanthine Prepared by treating 1,3-dimethyl-7-(3-methyl-2-buten-1-yi)-8-[cis-2-(tert.-butyloxycarbonylami no)-cyclohexylamino]-xanthine with sodium hydride in dimethylformamide at 0 C and subsequently reacting with methyliodide at 0 C to ambient temperature.
Rf value: 0.42 (silica gel, cyclohexane/ethyl acetate = 1:1) The following compound is obtained analogously to Example L:

(1) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-{N-[2-(tert.-butyloxycarbonylamino)-2-methyl-propyl]-N-methyl-amino}-xanthine Rf value: 0.62 (silica gel, methylene chloride/methanol = 95:5) Mass spectrum (ESI+): m/z = 449 [M+H]+

Example LI
2-(tert.-butyloxycarbonylamino)-3-(N-benzyl-N-methyl-amino)-propionic acid Prepared by reacting 3-(tert.-butyloxycarbonylamino)-oxetan-2-one with N-benzyl-N-methyl-amine in acetonitrile at ambient temperature.
Rf value: 0.40 (silica gel, methylene chloride/methanol = 9:1) Mass spectrum (ESI+): m/z = 309 [M+H]+

Example LII
1-(2-{3-[(methylamino)thiocarbonylamino]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-vl)-8-13-(tert-butyloxvcarbonvlamino)-piperidin-l-vll-xanthine Prepared by reacting 1-[2-(3-amino-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine with methylisothiocyanate in dimethylformamide at 90 C.
Rf value: 0.34 (silica gel, cyclohexane/ethyl acetate/methanol = 7:2:1) Mass spectrum (ESI+): m/z = 639 [M+H]+

The following compound is obtained analogously to Example LII:

(1) 1-(2-{3-[(aminocarbonyl)amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yi)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Reaction carried out with trimethylsilyl isocyanate.
Mass spectrum (ESI+): m/z = 609 [M+H]+
Example LIII
1-(2-{3-[(methoxycarbonyl)methylamino]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-vl)-8-[(3-(tert.-butyloxvcarbonylamino)-piperidin-l -yll-xanthine Prepared by reacting 1-[2-(3-amino-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine with methyl bromoacetate in the presence of potassium carbonate in dimethylformamide at 80 C.
Rf value: 0.38 (silica gel, cyclohexane/ethyl acetate = 3:7) Mass spectrum (ESI+): m/z = 638 [M+H]+
Example LIV
1-[2-(2-hydroxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-l-yl)-8-chloro-xanthine Prepared by treating 1-[2-(2-methoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-buten-l-yl)-8-chloro-xanthine with boron tribromide in methylene chloride. The desired product is contaminated with about 20 % of 1-[2-(2-hydroxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-brom-3-methyl-butyl)-8-chloro-xanthine.

Mass spectrum (ESI+): m/z = 403, 405 [M+H]+
Example LV
1-methyl-3-f2-(4-methoxy-phenyl)-ethyll-7-(2-cyano-benzyl)-8-chloro-xanthine Prepared by reacting 1-methyl-7-(2-cyano-benzyl)-8-chloro-xanthine with 2-(4-methoxy-phenyl)-ethanol in the presence of triphenylphosphine and diethyl azodicarboxylate in tetrahydrofuran at ambient temperature.
Mass spectrum (ESI+): m/z = 450 [M+H]+
Example LVI
7-(2-cyano-benzyl)-xanthine Prepared by treating 16.68 g of 2-amino-7-(2-cyano-benzyl)-1,7-dihydro-purin-6-one with 17.00 g of sodium nitrite in a mixture of 375 ml of conc. acetic acid, 84 ml of water and 5.2 ml of conc. hydrochloric acid at 50 C.
Yield: 8.46 g (50 % of theory) Mass spectrum (ESI+): m/z = 268 [M+H]+
Example LVII
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-benzylbromide in dimethylsulphoxide at 60 C and subsequently treating with 57 ml of conc. hydrochloric acid.
Yield: 18.00 g (97% of theory) Mass spectrum (ESI+): rn/z = 267 [M+H]+
Example LVIII
1-(4-oxo-4H-chromen-3-yl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[(3-(tert.-butyloxycarbonylamino)-pigeridin-1-vll-xanthine Prepared by reacting 1-[2-(2-hydroxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine with dimethylformamide-dimethylacetal in the presence of pyridine in toluene by refluxing.
Mass spectrum (ESI+): rn/z = 577 [M+H]+

Example LIX
Endo-6-amino-2-benzyl-2-aza-bicyclo[2.2.2]octane and exo-6-amino-2-benzyl-2-aza-bicyclo[2.2.21octane Prepared by reacting 2-benzyl-2-aza-bicycb[2.2.2]octan-6-one (R. F. Borne et al., J.
Het. Chem. 1973, 10, 241) with ammonium acetate in the presence of glacial acetic acid and molecular sieve 4A in methanol and subsequently treating with sodium cyanoborohydride at ambient temperature. A mixture of endo- and exo-compound is obtained which is separated by chromatography after reaction with di-tert.
butyl pyrocarbonate (cf Example IV(9) ).
Mass spectrum (ESI+): m/z = 217 [M+H]+
Example LX
3-Amino-3-(ovrrolidin-1-ylcarbonyl)-piperidine x trifluoroacetic acid Prepared by treating 1-(tert.-butyloxycarbonyl)-3-amino-3-(pyrrolidin-1-yicarbonyl) piperidine with trifluoroacetic acid in methylene chloride at ambient temperature.
The following compound is obtained analogously to Example LX:

(1) 3-amino-4-hydroxy-piperidin x trifluoroacetic acid Mass spectrum (El): m/z = 116 [M]+

Example LXI
1-(tert.-butvloxycarbonyl)-3-amino-3-(pvrrolidin-1-vlcarbonyl)-piperidine Prepared by treating 1-(tert.-butyloxycarbonyl)-3-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}-3-(pyrrolidin-1-yicarbonyl)-piperidine with diethylamine in tetrahydrofuran at ambient temperature.
Melting point: 108.5 C

Example LXII
1 -(tert.-butyloxycarbonyl)-3-benzylamino-4-hydroxy-piperidine and 1-(tert.-butyloxycarbonyl)-4-benzvlami no-3-hyd roxy-giperi di ne Prepared by refluxing 3.10 g of 3-(tert.-butyloxycarbonyl)-7-oxa-3-aza-bicyclo[4.1.0]heptane with 1.7 ml of benzylamine in 30 ml of ethanol. The regio-isomers formed can be separated by chromatography over a silica gel column with ethyl acetate/methanol/conc. aqueous ammonia (90:10:1) as eluant:

1 -(tert.-butyloxycarbonyl)-4-benzylamino-3-hydroxy-piperidine Yield: 0.68 g (14% of theory) Rf value: 0.68 (silica gel, ethyl acetate/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): rn/z = 307 [M+H]+

1 -(tert.-butyloxycarbonyl)-3-benzylamino-4-hydroxy-piperidine Yield: 1.13 g (24% of theory) Rf value: 0.56 (silica gel, ethyl acetate/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 307 [M+H]+

Example LXIII
1,3-dimethyl-2-thioxo-7-benzyl-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine Prepared by reacting potassium {3-methyl-7-benzyl-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine}-2-thiolate with dimethylsulphate in a mixture of water and dimethylformamide. The desired product is separated by chromatography from the 2-methylsulphanyl-3-methyl-7-benzyl-8-(3-amino-piperidin-1-yi)-xanthine which is also formed.
Mass spectrum (El): m/z = 484 [M]+

Preparation of the final compounds:

Example 1 1,3-dimethyl-7-benzvl-8-(3-amino-gyrrolidin-1-vl)-xanthine A mixture of 200 mg of 1,3-dimethyl-7-benzyl-8-chloro-xanthine, 420 mg of 3-amino-pyrrolidine-dihydrochloride, 0.92 ml of triethylamine and 2 ml of dimethylformamide is stirred for 2 days at 50 C. The reaction mixture is diluted with 20 ml of water and extracted twice with 10 ml of ethyl acetate. The organic phase is washed with saturated saline solution, dried and evaporated down. The residue is crystallised with diethylether/diisopropylether (1:1). The solid is suction filtered and dried.
Yield: 92 mg (40 % of theory) Melting point: 150 C
Mass spectrum (ESI+): m/z = 355 [M+H]+
Rf value: 0.08 (silica gel, ethyl acetate/methanol/conc. aqueous ammonia =
9:1:0.1) The following compounds are obtained analogously to Example 1:

(1) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-pyrrolidin-1-yl)-xanthine Melting point: 119 C
Mass spectrum (ESI+): rn/z = 333 [M+H]+
Rf value: 0.07 (silica gel, ethyl acetate/methanol/conc. aqueous ammonia =
9:1:0.1) (2) 1,3-dimethyl-7-benzyl-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): rn/z = 369 [M+H]+
Rf value: 0.06 (silica gel, ethyl acetate/methanol/conc. aqueous ammonia =
9:1:0.1) (3) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-[(trans-2-amino-cyclohexyl)amino]-xanthine Mass spectrum (ESI+): m/z = 361 [M+H]+

(4) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): rn/z = 347 [M+H]+

(5) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-(4-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 347 [M+H]+

(6) 1,3-di methyl-7-(3-methyl-2-buten-1-yl)-8-[(cis-2-amino-cyclohexyl)amino]-xanthine Mass spectrum (ESI+): rn/z = 361 [M+H]+

(7) 1,3-dimethyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 331 [M+H]+
Rf value: 0.08 (silica gel, ethyl acetate/methanol/conc. aqueous ammonia =
9:1:0.1) (8) 1,3-dimethyl-7-[(1-cyclopenten-1-yl)methyl]-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 359 [M+H]+
Rf value: 0.09 (silica gel, ethyl acetate/methanol/conc. aqueous ammonia =
9:1:0.1) (9) 1,3-dimethyl-7-(2-thienylmethyl)-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 375 [M+H]+
Rf value: 0.08 (silica gel, ethyl acetate/methanol/conc. aqueous ammonia =
9:1:0.1) (10) 1,3-dimethyl-7-(3-fluorobenzyl)-8-(3-amino-piperidin-1-yi)-xanthine Mass spectrum (ESI+): rn/z = 387 [M+H]+
Rf value: 0.08 (silica gel, ethyl acetate/methanol/conc. aqueous ammonia =
9:1:0.1) (11) 1,3-dimethyl-7-(2-fluorobenzyl)-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 387 [M+H]+
Rf value: 0.08 (silica gel, ethyl acetate/methanol/conc. aqueous ammonia =
9:1:0.1) (12) 1,3-dimethyl-7-(4-fluorobenzyl)-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 387 [M+H]+

(13) 1,3-dimethyl-7-(2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESi+): m/z = 333 [M+H]+

(14) 1,3-bis-(cyclopropylmethyl)-7-benzyl-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 449 [M+H]+

(15) 3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-l-yl)-xanthine Mass spectrum (ESI+): m/z = 333 [M+H]+

(16) 1-ethyl-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-l-yl)-xanthine Mass spectrum (ESI+): m/z = 361 [M+H]+

(17) 1-propyl-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-l-yl)-xanthine Mass spectrum (ESI+): m/z = 375 [M+H]+

(18) 1-butyl-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-l -yl)-xanthine Mass spectrum (ESI+): m/z = 389 [M+H]+

(19) 1-(2-propyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): rn/z = 375 [M+H]+

(20) 1-(2-methylpropyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-l-yl)-xanthine Mass spectrum (ESI+): m/z = 389 [M+H]+

(21) 1-(2-propen-1-yl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 373 [M+H]+

(22) 1-(2-propyn-1-yl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 371 [M+H]+

(23) 1-(cyclopropylmethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 387 [M+H]+

(24) 1-benzyl-3-methyl-7-(3-methyl-2-buten-1-yi)-8-(3-amino-piperidin-l -yl)-xanthine Mass spectrum (ESI+): m/z = 423 [M+H]+

(25) 1-(2-phenylethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 437 [M+H]+

(26) 1-(3-phenylpropyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 451 [M+H]+

(27) 1-(2-hydroxyethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 377 [M+H]+

(28) 1-(2-methoxyethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 391 [M+H]+

(29) 1-(3-hydroxypropyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-l-yl)-xanthine Mass spectrum (ESI+): m/z = 391 [M+H]+

(30) 1-[2-(dimethylamino)ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 404 [M+H]+

(31) 1-[3-(dimethylamino)propyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 418 [M+H]+

(32) 1-methyl-3-(cyclopropylmethyl)-7-benzyl-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 409 [M+H]+

(33) 1,3-diethyl-7-benzyl-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 397 [M+H]+

(34) 1-methyl-3-ethyl-7-benzyl-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 383 [M+H]+

(35) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-[N-(2-aminoethyl)-methylamino]-xanthine Mass spectrum (ESI+): m/z = 321 [M+H]+

(36) 1-[2-(2,4,6-trimethyl-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Melting point: 153-154.5 C
Mass spectrum (ESI+): rn/z = 479 [M+H]+

(37) 1-[2-(2,4-dichloro-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Melting point: 130-132T
Mass spectrum (ESI+): m/z = 505, 507, 509 [M+H]+

(38) 1-[2-(thiophen-2-yi)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.20 (silica gel, ethyl acetate/methanol/conc. aqueous ammonia =
5:1:0.1) Mass spectrum (ESI+): rn/z = 443 [M+H]+

(39) 1-[2-(thiophen-3-yl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidi n-1-yl)-xanthine Rf value: 0.20 (silica gel, ethyl acetate/methanol/conc. aqueous ammonia =
5:1:0.1) Mass spectrum (ESI+): m/z = 443 [M+H]+

(40) 1-[2-(4-tert.-butyl-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-l -yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.25 (silica gel, ethyl acetate/methanol/conc. aqueous ammonia =
5:1:0.1) Mass spectrum (ESI+): m/z = 493 [M+H]+

(41) 1-[2-(4-fluoro-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.20 (silica gel, ethyl acetate/methanol/conc. aqueous ammonia =
5:1:0.1) Mass spectrum (ESI+): m/z = 455 [M+H]+

(42) 1-[2-(4-methoxy-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidi n-1-yl)-xanthine Rf value: 0.18 (silica gel, ethyl acetate/methanol/conc. aqueous ammonia =
5:1:0.1) Mass spectrum (ESI+): m/z = 467 [M+H]+

(43) 1-methyl-3,7-dibenzyl-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 445 [M+H]+

(44) 1-methyl-3-[(methoxycarbonyl)-methyl]-7-benzyl-8-(3-amino-pipendin-1-yl)-xanthine Rf value: 0.27 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
9:1:0.1) Mass spectrum (ESI+): rrVz = 427 [M+H]+

(45) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-[N-(2-methylamino-ethyl)-N-methyl-amino]-xanthine Mass spectrum (ESI+): m/z = 335 [M+H]+

(46) 1,3-dimethyl-7-(3-methyl-2-buten-1 -yl)-8-[N-(2-dimethylamino-ethyl)-N-methyl-amino]-xanthine Mass spectrum (ESI+): rt/z = 349 [M+H]+

(47) 1-methyl-3-isopropyl-7-benzyl-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.32 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
9:1:0.1) Mass spectrum (ESI+): m/z = 397 [M+H]+

(48) 1,3-dimethyl-7-(2-pentyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): rn/z = 345 [M+H]+

(49) 1-methyl-3-(2-methoxy-ethyl)-7-benzyl-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.31 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
9:1:0.1) Mass spectrum (ESI+): rn/z = 413 [M+H]+

(50) 1-methyl-3-cyanomethyl-7-benzyl-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.24 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
9:1:0.1) Mass spectrum (ESI+): m/z = 394 [M+H]+

(51) 1-[2-(2-fluoro-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.30 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
10:1:0.1) Mass spectrum (ESI+): rrVz = 455 [M+H]+

(52) 1-[2-(2-methyl-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.34 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
10:1:0.1) Mass spectrum (ESI+): m/z = 451 [M+H]+

(53) 1-methyl-3-(2-propyn-1-yl)-7-benzyl-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.23 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
9:1:0.1) Mass spectrum (ESI+): m/z = 393 [M+H]+

(54) 1-methyl-3-(2-propen-1-yl)-7-benzyl-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.31 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
9:1:0.1) Mass spectrum (ESI+): m/z = 395 [M+H]+

(55) 1-[2-(3-methyl-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1 -yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.20 (silica gel, ethyl acetate/methanol/conc. aqueous ammonia =
7:3:0.1) Mass spectrum (ESI+): m/z = 451 [M+H]+

(56) 1-[2-(1-naphthyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1 -yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.30 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
15:1:0.1) Mass spectrum (ESI+): m/z = 487 [M+H]+

(57) 1-[2-(2-naphthyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.25 (silica gel, ethyl acetate/methanol/conc. aqueous ammonia =
7:3:0.1) Mass spectrum (ESI+): m/z = 487 [M+H]+

(58) 1-(4-phenyl-butyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-l -yl)-xanthine Rf value: 0.22 (silica gel, ethyl acetate/methanol/conc. aqueous ammonia =
7:3:0.1) Mass spectrum (ESI+): m/z = 465 [M+H]+

(59) 1-[2-(3-trifluoromethyl-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.30 (silica gel, ethyl acetate/methanol/conc. aqueous ammonia =
7:3:0.1) Mass spectrum (ESI+): m/z = 505 [M+H]+

(60) 1-[2-(pyridin-2-yl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yi)-8-(3-amino-piperidin-1-yl)-xanthine Melting point: 117-120 C
Mass spectrum (ESI+): m/z = 438 [M+H]+

(61) 1-[2-(pyrrol-1-yl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Melting point: 136-138.6 C
Mass spectrum (ESI+): m/z = 426 [M+H]+

(62) 1,3-dimethyl-7-(3-methyl-phenyl)-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): mlz = 369 [M+H]+

(63) 1-[2-([1,2,3]triazol-1-yl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.15 (silica gel, ethyl acetate/methanol/conc. aqueous ammonia =
7:3:0.1) Mass spectrum (ESI+): m/z = 428 [M+H]+

(64) 1-[2-(pyridin-4-yl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.12 (silica gel, ethyl acetate/methanol/conc. aqueous ammonia =
7:3:0.1) Mass spectrum (ESI+): m/z = 438 [M+H]+

(65) 1-(3-butyn-1-yl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Melting point: 150-152 C
Mass spectrum (ESI+): m/z = 385 [M+H]+

(66) 1-(3-butene-1-yl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-l -yl)-xanthine Melting point: 111-112.6 C
Mass spectrum (ESI+): m/z = 387 [M+H]+

(67) 1-(4-pentyn-1-yl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.12 (silica gel, ethyl acetate/methanol/conc. aqueous ammonia =
8:2:0.1) Mass spectrum (ESI+): m/z = 399 [M+H]+

(68) 1-(2-phenyl-ethyl)-3-methyl-7-benzyl-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 459 [M+H]+

(69) 1-(2-phenyl-ethyl)-3-methyl-7-cyclopropyimethyl-8-(3-amino-piperidin- l -yl)-xanthine Mass spectrum (ESI+): m/z = 423 [M+H]+

(70) 1-methyl-3-(2-phenyl-ethyl)-7-benzyl-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.23 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
9:1:0.1) Mass spectrum (ESI+): m/z = 459 [M+H]+

(71) 1-(2-phenyl-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 421 [M+H]+

(72) 1-(4-penten-1-yl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-l -yl)-xanthine Rf value: 0.18 (silica gel, ethyl acetate/methanol/conc. aqueous ammonia =
7:3:0.1) Mass spectrum (ESI+): m/z = 401 [M+H]+

(73) 1,3-dimethyl-7-benzyl-8-(homopiperazin-1-yl)-xanthine Rf value: 0.33 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:0.1) Mass spectrum (ESI+): rn/z = 369 [M+H]+

(74) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-{[(piperidin-2-yl)methyl]-amino}-xanthine Rf value: 0.24 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 361 [M+H]+

(75) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-{(R)-[2-(aminomethyl)-pyrrolidin-1-yl]}-xanthine Rf value: 0.27 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 347 [M+H]+

(76) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-{(S)-[2-(aminomethyl)-pyrrolidin-1-yl]}-xanthine Melting point: 112-115 C
Mass spectrum (ESI+): m/z = 347 [M+H]+

(77) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-[cis-(2-methylamino-cyclohexyl)amino]-xanthine Melting point: 172.5-175 C
Mass spectrum (ESI+): m/z = 375 [M+H]+

(78) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-(homopiperazin-1-yl)-xanthine Rf value: 0.31 (silica gel, ethyl acetate/methanol/conc. aqueous ammonia =
90:10:1) -Mass spectrum (ESI+): m/z = 347 [M+H]+

(79) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-[N-((S)-2-amino-propyl)-N-methyl-amino]-xanthine Carried out with sodium carbonate and Hunig base in dimethylsuiphoxide at 150 C
in a Roth bomb Rf value: 0.31 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 335 [M+H]+

(80) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-(piperazin-1-yl)-xanthine Rf value: 0.42 (silica gel, methylene chloride/methanol = 9:1) Mass spectrum (ESI+): m/z = 333 [M+H]+

(81) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-[N-((R)-2-amino-propyl)-N-methyl-amino]-xanthine Carried out with sodium carbonate and Hunig base in dimethylsulphoxide at 150 C
in a Roth bomb Melting point: 101-104.5 C
Mass spectrum (ESI+): rr/z = 335 [M+H]+

(82) 1-[2-(pyridin-3-yl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 438 [M+H]+
Rf value: 0.18 (silica gel, ethyl acetate/methanol/conc. aqueous ammonia =
7:3:0.1) (83) 1-[2-(4-methyl-thiazol-5-yl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 458 [M+H]+
Rf value: 0.14 (silica gel, ethyl acetate/methanol/conc. aqueous ammonia =
7:3:0.1) (84) 1-methyl-3-(2-dimethylamino-ethyl)-7-benzyl-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.18 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
9:1:0.1) Mass spectrum (ESI+): m/z = 426 [M+H]+
(85) 1-cyanomethyl-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.33 (silica gel, ethyl acetate/methanol/conc. aqueous ammonia =
7:3:0.1) Mass spectrum (ESI+): m/z = 372 [M+H]+
(86) 1 -[2-(3-methoxY-PhenYI)-ethY1]-3 methY1-7-(3 methY1-2 buten-1-Y1)-8-(3 amino-piperidin-1-yl)-xanthine Melting point: 118.5-119.5 C
Mass spectrum (ESI+): m/z = 467 [M+H]+
(87) 1-[2-(3-bromo-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Melting point: 116.5-117.5 C
Mass spectrum (ESI+): rn/z = 515, 517 [M+H]+
(88) 1-[2-(3-chloro-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.21 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
9:1:0.1) Mass spectrum (ESI+): m/z = 471, 473 [M+H]+
(89) 1,3-dimethyl-7-((E)-1-hexen-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 361 [M+H]+
(90) 1-((E)-2-phenyl-vinyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.11 (silica gel, ethyl acetate/methanol/conc. aqueous ammonia =
7:3:0.1) Mass spectrum (ESI+): n-/z = 435 [M+H]+
(91) 1-[2-(2-chloro-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.25 (silica gel, ethyl acetate/methanol/conc. aqueous ammonia =
7:3:0.1) Mass spectrum (ESI+): m/z = 471, 473 [M+H]+
(92) 1,3-dimethyl-7-((E)-2-phenyl-vinyl)-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 381 [M+H]+
(93) 1-[2-(2-methoxY-phenYI)-ethY1]-3-methy1-7-(3-methy1-2-buten-1-y1)-8-(3 amino-piperidin-1-yl)-xanthine Rf value: 0.15 (silica gel, ethyl acetate/methanol/conc. aqueous ammonia =
7:3:0.1) Mass spectrum (ESI+): m/z = 467 [M+H]+
(94) 1-[2-(2-trifluoromethyl-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.16 (silica gel, ethyl acetate/methanol/conc. aqueous ammonia =
7:3:0.1) Mass spectrum (ESI+): m/z = 505 [M+H]+
(95) 1-[2-(2-bromo-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.15 (silica gel, ethyl acetate/methanol/conc. aqueous ammonia =
7:3:0.1) Mass spectrum (ESI+): m/z = 515, 517 [M+H]+
(96) 1-(2-phenyl-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(piperazin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 423 [M+H]+
(97) 1-(2-phenyl-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(homopiperazin-1-yl)-xanthine Mass spectrum (ESI+): rrdz = 437 [M+H]+
(98) 1-[2-(3-fluoro-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Melting point: 126.8-127.5 C
Mass spectrum (ESI+): m/z = 455 [M+H]+
(99) 1-[2-(3-nitro-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1 -yl)-8-(3-amino-piperidin-1 -yl)-xanthine Melting point: 120.8-122 C
Mass spectrum (ESI+): m/z = 482 [M+H]+
(100) 1-[2-(4-methyl-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Melting point: 129-130.2 C
Mass spectrum (ESI+): m/z = 451 [M+H]+
(101) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-(3-aminomethyl-pyrrolidin-l -yl)-xanthine Rf value: 0.50 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 347 [M+H]+
ell, (102) 1,3-dimethyl-7-[(thiophen-3-yl)-methyl]-8-(piperazin-l-yl)-xanthine (Carried out in tetrahydrofuran at 60 C) Rf value: 0.14 (silica gel, methylene chloride/methanol = 9:1) Mass spectrum (ESI+): m/z = 361 [M+H]+
(103) 1,3-dimethyl-7-[(thiophen-2-yl)-methyl]-8-(piperazin-1-yl)-xanthine (Carried out in tetrahydrofuran at 60 C) Rf value: 0.19 (silica gel, methylene chloride/methanol = 9:1) Mass spectrum (ESI+): m/z = 361 [M+H]+
(104) 1,3-dimethyl-7-[(furan-3-yl)-methyl]-8-(piperazin-1-yl)-xanthine (Carried out in tetrahydrofuran at 60 C) Rf value: 0.13 (silica gel, methylene chloride/methanol = 9:1) Mass spectrum (ESI+): m/z = 345 [M+HJ+
(105) 1,3-dimethyl-7-[(furan-2-yl)-methyl]-8-(piperazin-1-yl)-xanthine (Carried out in tetrahydrofuran at 60 C) Rf value: 0.13 (silica gel, methylene chloride/methanol = 9:1) Mass spectrum (ESI+): m/z = 345 [M+H]+
(106) 1,3-dimethyl-7-(2-propyn-1-yl)-8-(piperazin-1-yl)-xanthine (Carried out in tetrahydrofuran at 60 C) Rf value: 0.16 (silica gel, methylene chloride/methanol = 9:1) Mass spectrum (ESI+): rn/z = 303 [M+H]+
(107) 1,3-dimethyl-7-(2,3-dimethyl-2-buten-1-yl)-8-(piperazin-1-yl)-xanthine (Carried out in tetrahydrofuran at 60 C) Rf value: 0.24 (silica gel, methylene chloride/methanol = 9:1) Mass spectrum (ESI+): rr/z = 347 [M+H]+
(108) 1,3-dimethyl-7-((E)-2-methyl-2-buten-1-yl)-8-(piperazin-1-yl)-xanthine (Carried out in tetrahydrofuran at 60 C) Rf value: 0.27 (silica gel, methylene chloride/methanol = 9:1) Mass spectrum (ESI+): m/z = 333 [M+H]+
(109) 1,3-dimethyl-7-[(1-cyclohexen-1-yl)-methyl]-8-(piperazin-1-yl)-xanthine (Carried out in tetrahydrofuran at 60 C) Rf value: 0.17 (silica gel, methylene chloride/methanol = 9:1) Mass spectrum (ESI+): m/z = 359 [M+H]+
(110) 1,3-dimethyl-7-[(1-cyclopenten-1-yl)-methyl]-8-(piperazin-1-yl)-xanthine (Carried out in tetrahydrofuran at 60 C) Rf value: 0.19 (silica gel, methylene chloride/methanol = 9:1) Mass spectrum (ESI+): rn/z = 345 [M+H]+
(111) 1,3-dimethyl-7-((Z)-2-methyl-2-buten-1 -yl)-8-(piperazin-1 -yl)-xanthine (Carried out in tetrahydrofuran at 60 C) Rf value: 0.23 (silica gel, methylene chloride/methanol = 9:1) Mass spectrum (ESI+): m/z = 333 [M+H]+
(112) 1,3-dimethyl-7-((E)-2-hexen-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 361 [M+H]+
(113) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-((S)-2-aminomethyl-azetidin-l-yl)-xanthine Rf value: 0.52 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 333 [M+H]+
(114) 1,3-dimethyl-7-((E)-1-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 333 [M+H]+
(115) 1,3,7-trimethyl-8-(3-amino-piperidin-1-yl)-xanthine Carried out with potassium carbonate in dimethylformamide Melting point: 147 C
Mass spectrum (ESI+): m/z = 293 [M+H]+
(116) 1,3-dimethyl-7-(2-naphthyl)-8-(3-amino-piperidin-1-yl)-xanthine Carried out with potassium carbonate in dimethylformamide Mass spectrum (ESI+): m/z = 405 [M+H]+
(117) 1,3-dimethyl-7-phenyl-8-(3-amino-piperidin-1-yl)-xanthine Carried out with potassium carbonate in dimethylformamide Mass spectrum (ESI+): m/z = 355 [M+H]+
(118) 1,3-dimethyl-7-(3,5-dimethyl-phenyl)-8-(3-amino-piperidin-1-yl)-xanthine Carried out with potassium carbonate in dimethylformamide Mass spectrum (ESI+): rrVz = 383 [M+H]+
(119) 1,3-dimethyl-7-[(2-naphthyl)methyl]-8-(3-amino-piperidin-1-yl)-xanthine Carried out with potassium carbonate in dimethylformamide Mass spectrum (ESI+): m/z = 419 [M+H]+
(120) 1,3-dimethyl-7-[(1-naphthyl)methyl]-8-(3-amino-piperidin-1-yl)-xanthine Carried out with potassium carbonate in dimethylformamide Mass spectrum (ESI+): m/z = 419 [M+H]+
(121) 1,3-dimethyl-7-(2-cyano-benzyl)-8-(3-amino-piperidin-1-yl)-xanthine Carried out with potassium carbonate in dimethylformamide Mass spectrum (ESI+): m/z = 394 [M+H]+
(122) 1,3-dimethyl-7-(4-methyl-phenyl)-8-(3-amino-piperidin-1-yl)-xanthine Carried out with potassium carbonate in dimethylformamide Mass spectrum (ESI+): m/z = 369 [M+H]+
(123) 1,3-dimethyl-7-(3-cyano-benzyl)-8-(3-amino-piperidin-1-yi)-xanthine Carried out with potassium carbonate in dimethylformamide Mass spectrum (ESI+): m/z = 394 [M+H]+
(124) 1,3-dimethyl-7-(3,5-difluoro-benzyl)-8-(3-amino-piperidin-1-yl)-xanthine Carried out with potassium carbonate in dimethylformamide Mass spectrum (ESI+): m/z = 405 [M+H]+
(125) 1,3-dimethyl-7-(4-cyano-benzyl)-8-(3-amino-piperidin-1-yl)-xanthine Carried out with potassium carbonate in dimethylformamide Mass spectrum (ESI+): m/z = 394 [M+H]+
(126) 1,3-dimethyl-7-(3-nitro-benzyl)-8-(3-amino-piperidin-l-yl)-xanthine Carried out with potassium carbonate in dimethylformamide Mass spectrum (ESI+): m/z = 414 [M+H]+
(127) 1,3-dimethyl-7-(4-nitro-benzyl)-8-(3-amino-piperidin-1-yi)-xanthine Carried out with potassium carbonate in dimethylformamide Mass spectrum (ESI+): m/z = 414 [M+H]+
(128) 1,3-dimethyl-7-(2-nitro-benzyl)-8-(3-amino-piperidin-l-yl)-xanthine Carried out with potassium carbonate in dimethylformamide Mass spectrum (ESI+): m/z = 414 [M+H]+
(129) 1,3-dimethyl-7-(3-trifluoromethyl-phenyl)-8-(3-amino-piperidin-l -yl)-xanthine Carried out with potassium carbonate in dimethylformamide Mass spectrum (ESI+): m/z = 423 [M+H]+
(130) 1,3-dimethyl-7-(3-cyano-phenyl)-8-(3-amino-piperidin-1-yl)-xanthine Carried out with potassium carbonate in dimethylformamide Mass spectrum (ESI+): m/z = 380 [M+H]+
(131) 1-(2-phenyl-propyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-l-yl)-xanthine Carried out with potassium carbonate in dimethylsulphoxide Rf value: 0.50 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
80:20:1) Mass spectrum (ESI+): m/z = 451 [M+H]+
(132) 1,3-dimethyl-7-(3-fluoro-phenyl)-8-(3-amino-piperidin-1-yl)-xanthine Carried out with potassium carbonate in dimethylformamide Rf value: 0.10 (silica gel, methylene chloride/methanol = 9:1) Mass spectrum (ESI+): m/z = 373 [M+H]+
(133) 1-(2-methoxy-2-phenyl-ethyl)-3-methyl-7-(3-methyl-2-buten-1 -yl)-8-(3-amino-piperidin-1 -yl)-xanthine Carried out with potassium carbonate in dimethylsulphoxide Rf value: 0.20 (silica gel, ethyl acetate/methanol = 8:2) Mass spectrum (ESI+): rn/z = 467 [M+H]+
(134) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-(2-amino-2-methyl-propylamino)-xanthine Carried out with sodium carbonate in dimethylsulphoxide Melting point: 140.5-143 C
Mass spectrum (ESI+): m/z = 335 [M+H]+
(135) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-((f-2-amino-propylamino)-xanthine Carried out with sodium carbonate in dimethylsulphoxide Melting point: 141-144 C
Mass spectrum (ESI+): m/z = 321 [M+H]+
(136) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-((S)-2-amino-propylamino)-xanthine Carried out with potassium tert. butoxide and sodium carbonate in dimethylsulphoxide Melting point: 142-145 C
Mass spectrum (ESI+): m/z = 321 [M+H]+
(137) 1,3-dimethyl-7-(2-cyano-benzyl)-8-(homopiperazin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 394 [M+H]+
Rf value: 0.10 (silica gel, methylene chloride/methanol = 9:1) (138) 1,3-dimethyl-7-(2-iod-benzyl)-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 495 [M+H]+
(139) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-[3-amino-3-(pyrrolidin-1-ylcarbonyl)-piperidin-1-yl]-xanthine Carried out in the presence of sodium carbonate in dimethylsulphoxide.
Melting point: 159-160 C
Mass spectrum (ESI+): rrVz = 444 [M+H]+
(140) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-4-hydroxy-piperidin-1-yl)-xanthine Carried out in the presence of sodium carbonate in dimethylsulphoxide.
Rf value: 0.64 (Reversed Phase ready-made TLC plate (E. Merck), acetonitrile/water/ trifluoroacetic acid = 50:50:1) Mass spectrum (ESI+): rn/z = 363 [M+H]+
Example 2 (R)-1,3-dimethyl-7-(3-methyl-2-buten-1-y1)-8-(3-amino-pperidin-1-yl)-xanthine 980 mg of (R)-1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonyl-amino)-piperidin-1-yl]-xanthine in 12 ml methylene chloride are combined with 3 ml of trifluoroacetic acid and stirred for 2 hours at ambient temperature. Then the mixture is diluted with methylene chloride and made alkaline with 1 M sodium hydroxide solution. The organic phase is separated off, dried and evaporated to dryness.
Yield: 680 mg (89 % of theory) Mass spectrum (ESI+): m/z = 347 [M+H]+
Rf value: 0.20 (aluminium oxide, ethyl acetate/methanol = 9:1) The following compounds are obtained analogously to Example 2:

(1) (S')-1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 347 [M+H]+

(2) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-hexahydroazepin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 361 [M+H]' (3) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-(4-amino-hexahydroazepin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 361 [M+H]+

(4) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-(cis-3-amino-cyclohexyl)-xanthine-hydrochloride The reaction was carried out with hydrochloric acid.
'H-NMR (400 MHz, 6 mg in 0.5 ml DMSO-d6, 30 C): characteristic signals at 3.03 ppm (1 H, m, H-1) and 3.15 ppm (1 H, m, H-3) (5) 1,3-dimethyl-7-(3-methyl-2-buten-l-yl)-8-(3-aminopropyl)-xanthine The reaction was carried out with hydrochloric acid.
Mass spectrum (ESI+): m/z = 306 [M+H]+

(6) 1,3-dimethyl-7-(3-methyl-2-buten-1 -yl)-8-(3-amino-4-methyl-piperidin-1 -yl)-xanthine Mass spectrum (ESI+): m/z = 361 [M+H]+

(7) 1-methyl-3-(4-methoxy-benzyl)-7-benzyl-8-((S)-3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 475 [M+H]+
Rf value: 0.38 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
9:1:0.1) (8) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-[N-(2-aminoethyl)-N-ethyl-amino]-xanthine Mass spectrum (ESI+): nVz = 335 [M+H]+

(9) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-(piperidin-4-yl)-xanthine Mass spectrum (ESI+): m/z = 332 [M+H]+

(10) 1,3-dimethyl-7-(3-methyl-2-buten-1-yi)-8-(trans-2-amino-cyclohexyl)-xanthine Mass spectrum (ESI+): m/z = 346 [M+H]+

(11) 1 -methyl-3-hexyl-7-benzyl-8-((S)-3-amino-piperidin-1 -yl)-xanthine Rf value: 0.18 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
9:1:0.1) Mass spectrum (ESI+): m/z = 439 [M+H]+

(12) 1-methyl-3-(2-hydroxy-ethyl)-7-benzyl-8-((S)-3-amino-piperidin-1-yl)-xanthine Rf value: 0.19 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
9:1:0.1) Mass spectrum (ESI+): m/z = 399 [M+H]+

(13) 1-(2-phenyl-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 437 [M+H]+

(14) 1-(2-phenyl-ethyl)-3-methyl-7-(3-methyl-2-buten-1 -yl)-8-((R)-3-amino-piperidin-1 -yl)-xanthine Mass spectrum (ESI+): m/z = 437 [M+H]+

(15) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-[2-(aminomethyl)-piperidin-1-yl)]-xanthine Rf value: 0.34 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 361 [M+H]+

(16) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-[(pyrrolidin-3-yl)amino]-xanthine Carried out with hydrochloric acid in dioxan Rf value: 0.15 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 333 [M+H]+

(17) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-[N-(piperidin-3-yl)-N-methyl-amino]-xanthine Rf value: 0.44 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 361 [M+H]+

(18) 1-[2-(4-hydroxy-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-((S)-amino-piperidin-1-yl)-xanthine Carried out in tetrahydrofuran/water at 50-80 C
Rf value: 0.58 (ready-made reversed phase TLC plate(E. Merck), acetonitrile/water/
trifluoroacetic acid = 50:50:1) Mass spectrum (ESI+): m/z = 453 [M+H]+

(19) 1-[(methoxycarbonyl)-methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-((S')-3-amino-piperidin-1-yl)-xanthine Melting point: 102-105 C
Mass spectrum (ESI+): m/z = 405 [M+H]+

(20) 1-[3-(methoxycarbonyl)-propyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-((S)-amino-piperidin-1-yl)-xanthine Rf value: 0.15 (silica gel, methylene chloride/methanol = 9:1) Mass spectrum (ESI+): m/z = 433 [M+H]+

(21) 1-{2-[4-(ethoxycarbonyl)-phenyl]-ethyl}-3-methyl-7-(3-methyl-2-buten-1-yl)-8-((S')-3-amino-piperidin-1-yl)-xanthine Melting point: 142-144 C
Mass spectrum (ESI+): m/z = 509 [M+H]+

(22) 1-[2-(3-hydroxy-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-((S)-amino-piperidin-1-yl)-xanthine Carried out in tetrahydrofuran/water at 80 C
Melting point: 168-170 C

Mass spectrum (ESI+): rn/z = 453 [M+H]+

(23) 1-[2-(methoxycarbonyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine Rf value: 0.26 (silica gel, methylene chloride/methanol = 9:1) Mass spectrum (ESI+): m/z = 419 [M+H]+

(24) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-[(piperidin-4-yl)amino]-xanthine Mass spectrum (ESI+): m/z = 347 [M+H]+
Rf value: 0.25 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
9:1:0.1) (25) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-[(piperidin-3-yl)amino]-xanthine Mass spectrum (ESI+): m/z = 347 [M+H]+
Rf value: 0.13 (silica gel, methylene chloride/methanol = 9:1) (26) 1-phenyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): rn/z = 395 [M+H]+

(27) 1-phenyl-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-l -yl)-xanthine Rf value: 0.70 (aluminium oxide, methylene chloride/methanol = 19:1) Mass spectrum (ESI+): m/z = 409 [M+H]+

(28) 1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.16 (silica gel, ethyl acetate/methanol/conc. aqueous ammonia =
7:3:0.1) Mass spectrum (ESI+): m/z = 451 [M+H]+

(29) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-[N-(pyrrolidin-3-yl)-N-methyl-amino]-xanthine Rf value: 0.43 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 347 [M+H]+

(30) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-cyclohexyl)-xanthine (According to NMR spectrum cis/trans mixture = 65:35) Mass spectrum (ESI+): m/z = 346 [M+H]+

(31) 1,3-bis(2-phenyl-ethyl)-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.33 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 527 [M+H]+

(32) 1-(2-phenyl-ethyl)-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 423 [M+H]+

(33) 1-(2-phenyl-ethyl)-3-cyanomethyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.31 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 462 [M+H]+

(34) 1-(2-phenyl-ethyl)-3-[(methoxycarbonyl)-methyl]-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 495 [M+H]+

(35) 1-[2-(2-nitro-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.25 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 482 [M+H]+

(36) 1-[2-(3,5-difluoro-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Melting point: 162-163.5 C
Mass spectrum (ESI+): m/z = 473 [M+H]+

(37) 1-[2-(2-methoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yi)-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 481 [M+H]+

(38) 1-[2-(thiophen-3-yl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 457 [M+H]+

(39) 1-[2-(2,6-difluoro-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-l -yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.35 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 473 [M+H]+

(40) 1-[2-(4-methoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3--yl)-8-(3-amino-piperidin-1 -yl Mass spectrum (ESI+): m/z = 481 [M+H]+

(41) 1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 451 [M+H]+

(42) 1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1 -yl)-8-((R)-3-amino-piperidin-1 -yl)-xanthine Mass spectrum (ESI+): m/z = 451 [M+H]+

(43) 1-[2-(3,5-dimethyl-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.15 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 465 [M+H]+

(44) 1-(phenylsulphanyl methyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidi n-1-yl)-xanthine Rf value: 0.40 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 455 [M+H]+

(45) 1-(phenyl sulphinylmethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.42 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 471 [M+H]+

(46) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-(cis-2-amino-cyclopropylamino)-xanthine Mass spectrum (ESI+): m/z = 319 [M+H]+
Rf value: 0.55 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:0.1) (47) 1-[2-(3-methoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-l-yl)-xanthine Rf value: 0.14 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 481 [M+H]+

(48) 1-[2-(4-methyl-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-l -yl)-xanthine Rf value: 0.35 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 465 [M+H]+

(49) 1-(2-methoxycarbonyl-2-propen-1-yl)-3-methyl-7-(3-methyl-2-buten-l -yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.30 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 431 [M+H]+

(50) 1-(2-phenyl-ethyl)-3-(2-dimethylamino-ethyl)-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.15 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 494 [M+H]+

(51) 1-(2-phenyl-ethyl)-3-(2-propyn-1-yl)-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.71 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
80:20:1) Mass spectrum (ESI+): m/z = 461 [M+H]+
(52) 1-(2-phenyl-ethyl)-3-((E)-2-phenyl-vinyl)-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.27 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 525 [M+H]+

(53) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-(piperidin-3-yl)-xanthine Mass spectrum (ESI+): m/z = 332 [M+H]+

(54) 1-(2-phenyl-ethyl)-3-vinyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-pipendin-1-yl)-xanthine Rf value: 0.26 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): rn/z = 449 [M+H]+

(55) 1-(3-oxo-3-phenyl-propyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 465 [M+H]+

(56) 1-methyl-3-(2-phenyl-2-oxo-ethyl)-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.30 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 451 [M+H]+

(57) 1 -methyl -3-cyanomethyl-7- (3-methyl-2-buten- 1 -yl)-8-(3-ami no-pi pe rid i n- 1 -yl) -xanthine Rf value: 0.23 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): rn/z = 372 [M+H]+

(58) 1-methyl-3-(2-phenyl-ethyl)-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.20 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 437 [M+H]+

(59) 1-methyl-3-(2-dimethylamino-ethyl)-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.14 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
80:20:1) Mass spectrum (ESI+): m/z = 404 [M+H]+

(60) 1-methyl-3-isopropyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Melting point: 115-117 C
Mass spectrum (ESI+): m/z = 375 [M+H]+

(61) 1-(2-hydroxy-2-phenyl-ethyl)-3-methyl-7-(3-methyl-2-buten-1 -yl)-8-(3-amino-piperidin-1 -yl)-xanthine Rf value: 0.20 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 453 [M+H]+

(62) 1-methyl-3-(2-cyano-ethyl)-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Melting point: 146-149 C
Mass spectrum (ESI+): m/z = 386 [M+H]+

(63) 1-methyl-3-[2-(4-methoxy-phenyl)-ethyl]-7-(3-methyl-2-buten-1-yl)-8-(3-ami no-piperidin-1-yl)-xanthine Rf value: 0.34 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 467 [M+H]+

(64) 1-methyl-3-phenyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.38 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 409 [M+H]+

(65) 1-methyl-3-[2-(3-methoxy-phenyl)-ethyl]-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.35 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 467 [M+H]+

(66) 1-methyl-3-[2-(2-methoxy-phenyl)-ethyl]-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.31 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 467 [M+H]+

(67) 1-methyl-3-[2-(3-methyl-phenyl)-ethyl]-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.13 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 451 [M+H]+

(68) 1-methyl-3-[2-(4-methyl-phenyl)-ethyl]-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.16 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
95:5:1) Mass spectrum (ESI+): m/z = 451 [M+H]+

(69) 1-methyl-3-[2-(2-methyl-phenyl)-ethyl]-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.16 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
95:5:1) Mass spectrum (ESI+): m/z = 451 [M+H]+

(70) 1-methyl-3-[2-(2-fluoro-phenyl)-ethyl]-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.35 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 455 [M+H]+

(71) 1-(2-oxo-propyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine x trifluoroacetic acid (The product is isolated as the trifluoroacetate.) Mass spectrum (ESI+): m/z = 389 [M+H]+

(72) 1-methyl-3-(4-phenyl-butyl)-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.36 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 465 [M+H]+

(73) 1-methyl-3-(3-phenyl-propyl)-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-l -yl)-xanthine Rf value: 0.33 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 451 [M+H]+

(74) 1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-(2-cyano-benzyl)-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 498 [M+H]+

(75) 1-(2-phenyl-ethyl)-3-methyl-7-(2-cyano-benzyl)-8-(3-amino-piperidin-1-yi)-xanthine Mass spectrum (ESI+): m/z = 484 [M+H]+

(76) 1-(3-methoxycarbonyl-2-propen-1-yl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.35 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
80:20:1) Mass spectrum (ESI+): rn/z = 431 [M+H]+

(77) 1-methyl-3-[2-(4-fluoro-phenyl)-ethyl]-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidi n-1-yl)-xanthine Rf value: 0.28 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 455 [M+H]+

(78) 1-methyl-3-[2-(3-fluoro-phenyl)-ethyl]-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.35 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 455 [M+H]+

(79) 1-[2-(2,5-dimethoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.29 (silica gel, ethyl acetate/methanol/conc. aqueous ammonia =
70:30:1) Mass spectrum (ESI+): m/z = 511 [M+H]+

(80) 1-[2-(4-fluoro-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-l -yl)-xanthine Rf value: 0.35 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
80:20:1) Mass spectrum (ESI+): rn/z = 469 [M+H]+

(81) 1-phenylcarbonylamino-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine (Contaminated with 1-phenylcarbonylamino-7-(3-methyl-butyl)-8-(3-amino-piperidin-1-yl)-xanthi ne) Rf value: 0.26 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
80:20:1) Mass spectrum (ESI+): rn/z = 438 [M+H]+

(82) 1-amino-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine (Contaminated with 1 -amino-7-(3-methyl-butyl)-8-(3-amino-piperidin-1 -yl)-xanthine) Rf value: 0.22 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
80:20:1) Mass spectrum (ESI+): m/z = 334 [M+H]+

(83) 1-[2-(3-methanesulphonyloxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 545 [M+H]+

(84) 1-[2-(3-allyloxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): rn/z = 507 [M+H]+

(85) 1-{2-oxo-2-[3-(2-propyn-1-yloxy)-phenyl]-ethyl}-3-methyl-7-(3-methyl-2-buten-l -yl)-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 505 [M+H]+

(86) 1-(3-methoxycarbonyl-2-propen-1-yl)-3-methyl-7-(2-cyano-benzyl)-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 478 [M+H]+

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

(88) 1-[2-(3-cyanomethoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 506 [M+H]+

(89) 1-[2-(3-benzyloxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 557 [M+H]+

(90) 1-[2-(3-phenyisulphonyloxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-l-yl)-xanthine Mass spectrum (ESI+): m/z = 607 [M+H]+

(91) 1-[2-(3-hydroxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 467 [M+H]+

(92) 1-[(pyridin-2-yl)methyl]-3-methyl-7-(2-cyano-benzyl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.20 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 471 [M+H]+

(93) 1-[2-(3-phenyloxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 543 [M+H]+

(94) 1-(2-phenyl-2-oxo-ethyl)-3-[(methoxycarbonyl)methyl]-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.29 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 509 [M+H]+

(95) 1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(piperazin-1-yl)-xanthine Rf value: 0.10 (silica gel, methylene chloride/methanol = 90:10) Mass spectrum (ESI+): m/z = 437 [M+H]+

(96) 1-[2-(3-amino-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-l -yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf.value: 0.25 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
80:20:1) Mass spectrum (ESI+): m/z = 466 [M+H]+

(97) 1-(2-{3-[bis(methanesulphonyl)-amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.45 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
80:20:1) Mass spectrum (ESI+): m/z = 622 [M+H]+

(98) 1-[2-(2-bromo-5-dimethylamino-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-l-yl)-xanthine Mass spectrum (ESI+): rn/z = 572, 574 [M+H]+

(99) 1-[2-(3-nitro-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-l -yl)-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 496 [M+H]+

(100) 1-[2-(3-methoxycarbonylamino-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-l-yl)-xanthine tell" Mass spectrum (ESI+): rr/z = 524 [M+H]+

(101) 1-[2-(3-acetylamino-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-l-yl)-8-(3-amino-piperidin-l-yl)-xanthine Mass spectrum (ESI+): m/z = 508 [M+H]+

(102) 1-[2-(3-{[(ethoxycarbonylamino)carbonyl]amino}-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yi)-8-(3-amino-piperidin-l-yl)-xanthine Mass spectrum (ESI+): rn/z = 581 [M+H]+

(103) 1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1 -yl)-8-(homopiperazin-1 -yl)-xanthine Rf value: 0.10 (silica gel, methylene chloride/methanol = 90:10) Mass spectrum (ESI+): m/z = 451 [M+H]+

(104) 1-[2-(3-cyanomethylamino-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.35 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
80:20:1) Mass spectrum (ESI+): m/z = 505 [M+H]+

"" 1 ,3-dimeth 1-7-3 meth 1-2 buten-1-Y)!-8-(4aminomethYI-PPeridin-l- I
(105) Y( Y Y)-xanthine Carried out with isopropanolic hydrochloric acid (5-6M) in methylene chloride Melting point: 110-112 C
Mass spectrum (ESI+): m/z = 361 [M+H]+

(106) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-(3-aminomethyl-piperidin-l -yl)-xanthine Carried out with isopropanolic hydrochloric acid (5-6M) in methylene chloride.
Rf value: 0.48 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:0.1) Mass spectrum (ESI+): m/z = 361 [M+H]+

(107) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-(trans-2-amino-cyclobutylamino)-xanthine Carried out with isopropanolic hydrochloric acid (5-6M) in methylene chloride.
Rf value: 0.65 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:0.1) Mass spectrum (ESI+): m/z = 333 [M+H]+

(108) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-[N-((S)-2-amino-l -methyl-ethyl)-N-methyl-amino]-xanthine Carried out with isopropanolic hydrochloric acid (5-6M) in methylene chloride.

Melting point: 109.5-113 C
Mass spectrum (ESI+): m/z = 335 [M+H]+

(109) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-[N-((R)-2-amino-l -methyl-ethyl)-N-methyl-ami no]-xanthi ne Carried out with isopropanolic hydrochloric acid (5-6M) in methylene chloride.
Rf value: 0.50 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): rr/z = 335 [M+H]+

(110) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-[cis-N-(2-amino-cyclohexyl)-N-methyl-ami no]-xanthine Carried out with isopropanolic hydrochloric acid (5-6M) in methylene chloride.
Rf value: 0.71 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 375 [M+H]+

(111) 1,3-dimethyl-7-(3-methyl-2-buten-1 -yl)-8-(6-amino-[1,4]diazepan-1 -yl)-xanthine Carried out with isopropanolic hydrochloric acid (5-6M) in methylene chloride.
Rf value: 0.41 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 362 [M+H]+

(112) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-[N-(2-amino-2-methyl-propyl)-N-methyl-amino]-xanthine Carried out with isopropanolic hydrochloric acid (5-6M) in methylene chloride.
Melting point: 156.5-159.5 C
Mass spectrum (ESI+): m/z = 349 [M+H]+

(113) 1-[(pyridin-2-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Carried out with isopropanolic hydrochloric acid (5-6M) in methylene chloride.

Melting point: 136-139.5 C
Mass spectrum (ESI+): m/z = 424 [M+H]+

(114) 1-[(thiazol-2-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Carried out with isopropanolic hydrochloric acid (5-6M) in methylene chloride.
Melting point: 124-127 C
Mass spectrum (ESI+): nilz = 430 [M+H]+

(115) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-(trans-2-amino-cyclopentylamino)-xanthine Carried out with isopropanolic hydrochloric acid (5-6M) in methylene chloride.
Rf value: 0.25 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
95:5:0.1) Mass spectrum (ESI+): m/z = 347 [M+H]+

(116) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-(trans-3-amino-cyclohexylamino)-xanthine (contaminated with about 25% of cis compound) Carried out with isopropanolic hydrochloric acid (5-6M) in methylene chloride.
Rf value: 0.16 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI'): m/z = 359 [M-H]"

(117) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-(cis-3-amino-cyclohexylamino)-xanthine ( contaminated with about 21 % of trans compound) Carried out with isopropanolic hydrochloric acid (5-6M) in methylene chloride.
Rf value: 0.21 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI"): m/z = 359 [M-H]-(118) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-(cis-2-amino-cyclopentylamino)-xanthine Carried out with isopropanolic hydrochloric acid (5-6M) in methylene chloride.
Rf value: 0.25 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
95:5:0.1) Mass spectrum (ESI '): m/z = 347 [M+H]+

(119) 1-[(isoquinolin-1-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Carried out with isopropanolic hydrochloric acid (5-6M) in methylene chloride.
Melting point: 146-149 C
Mass spectrum (ESI+): m/z = 474 [M+H]+

(120) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-(cis-3-amino-cyclopentylamino)-xanthine Carried out with isopropanolic hydrochloric acid (5-6M) in methylene chloride.
Melting point: 146-148 C
Mass spectrum (ESI '): m/z = 347 [M+H]+

(121) 1-[(benzo[d]isothiazol-3-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Carried out with isopropanolic hydrochloric acid (5-6M) in methylene chloride.
Melting point: 129-131 C
Mass spectrum (ESI+): m/z = 480 [M+H]+

(122) 1-[(pyridin-3-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Carried out with isopropanolic hydrochloric acid (5-6M) in methylene chloride.
Rf value: 0.42 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): rn/z = 424 [M+H]+

(123) 1-[(pyridin-4-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Carried out with isopropanolic hydrochloric acid (5-6M) in methylene chloride.
Rf value: 0.48 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 424 [M+H]+

(124) 1-[(isoxazol-3-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Carried out with isopropanolic hydrochloric acid (5-6M) in methylene chloride.
Melting point: 124-127.5 C
Mass spectrum (ESI+): r /z = 414 [M+H]+

(125) 1-[(isoquinolin-1-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yi)-8-((R)-3-amino-piperidin-1-yl)-xanthine Carried out with isopropanolic hydrochloric acid (5-6M) in methylene chloride.
Rf value: 0.50 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 474 [M+H]+

(126) 1-[(isoquinolin-1-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine Carried out with isopropanolic hydrochloric acid (5-6M) in methylene chloride.
Mass spectrum (ESI+): m/z = 474 [M+H]+

(127) 1-[(1-naphthyl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Carried out with isopropanolic hydrochloric acid (5-6M) in methylene chloride.
Rf value: 0.51 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 473 [M+H]+

(128) 1-[(benzo[d]isoxazol-3-yl)methyl]-3-methyl-7-(3-methyl-2-buten-l -yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.20 (silica gel, methylene chloride/methanol = 9:1) Mass spectrum (ESI+): nyz = 464 [M+H]+

(129) 1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1 -yl)-8-(3-amino-methyl-piperidin-1 -yl)-xanthine Rf value: 0.18 (silica gel, ethyl acetate/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 465 [M+H]+

(130) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-3-methyl-piperidin-1-yl)--yl)-xanthine Rf value: 0.41 (aluminium oxide, methylene chloride/methanol = 20:1) Mass spectrum (ESI+): m/z = 361 [M+H]+

(131) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-[N-(2-amino-3-dimethylamino-3-oxo-propyl)-N-methyl-amino]-xanthine x trifluoroacetic acid Rf value: 0.31 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
40:10:1) Mass spectrum (ESI+): m/z = 392 [M+H]+

(132) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-[N-(2,3-diamino-3-oxo-propyl)-N-methyl-amino]-xanthine x trifluoroacetic acid Rf value: 0.28 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
40:10:1) Mass spectrum (ESI+): m/z = 364 [M+H]+

(133) 1-[(aminocarbonyl)methyl)]-3-methyl-7-(2-cyano-benzyl)-8-(3-amino-piperidin-1-yl)-xanthine Prepared from 1 -cyanomethyl-3-methyl-7-(2-cyano-benzyl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1 -yl]-xanthine. During the treatment with trifluoroacetic acid the protecting group is cleaved and the cyano group is hydrolysed to form the amide.

R f value: 0.10 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:0.1) Mass spectrum (ESI+): m/z = 437 [M+H]+

(134) 1-[2-(3-methanesulphonylamino-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 544 [M+H]+
Rf value: 0.45 (silica gel, methylene chloride/methanol/triethylamine =
90:10:0.1) (135) 1-[2-(2-nitro-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yi)-xanthine Mass spectrum (ESI+): m/z = 496 [M+H]+

(136) 1-[2-(2-ami no-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yi)-xanthine Mass spectrum (ESI+): m/z = 466 [M+H]+

(137) 1-(2-{3-[(methylamino)thiocarbonylami no]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.30 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
"" ,, 80:20:0.1) Mass spectrum (ESI+): m/z = 539 [M+H]+

(138) 1-[2-(2-acetylamino-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 508 [M+H]+

(139) 1-[(6-methyl-pyridi n-2-yl) methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Carried out with isopropanolic hydrochloric acid (5-6M) in methylene chloride.
Melting point: 127.5-130 C
Mass spectrum (ESI+): m/z = 438 [M+H]+

(140) 1-[(isoquinolin-4-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Carried out with isopropanolic hydrochloric acid (5-6M) in methylene chloride.
Rf value: 0.40 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 474 [M+H]+
(141) 1-[(1-methyl-1 H-indazol-3-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Carried out with isopropanolic hydrochloric acid (5-6M) in methylene chloride.
Rf value: 0.31 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 477 [M+H]+
(142) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-{N-[2-amino-3-oxo-3-(pyrrolidin-1-yl)-propyl]-N-methyl-amino}-xanthine Melting point: 138 C
Mass spectrum (ESI+): m/z = 418 [M+H]+
(143) 1,3-dimethY1-7-(3-methy1-2-buten-1-Y)1-8-[N-(2-amino-3-methYlamino-3-oxo-propyl)-N-methyl-amino]-xanthine Rf value: 0.20 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 378 [M+H]+
(144) 1-(2-{3-[(methoxycarbonyl)methylamino]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.29 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
80:20:0.1) Mass spectrum (ESI+): m/z = 538 [M+H]+

= -225-(145) 1-cyanomethyl-3-methyl-7-(2-cyano-benzyl)-8-(3-amino-piperidin-1-yl)-xanthine Carried out with isopropanolic hydrochloric acid (5-6M) in methylene chloride.
Rf value: 0.60 (silica gel, methylene chloride/methanol = 9:2) Mass spectrum (ESI+): m/z = 419 [M+H]+
(146) 1-[2-(2-hydroxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine x trifluoroacetic acid Mass spectrum (ESI+): m/z = 467 [M+H]+
(147) 1-[2-(2-methanesulphonyloxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 545 [M+H]+
(148) 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 spectrum (ESI+): rn/z = 539 [M+H]+
(149) 1-[2-(2-cyanomethoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 506 [M+H]+
(150) 1-(2-{3-[(dimethylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.45 (silica gel, methylene chloride/methanol/triethylamine =
80:20:0.1) Mass spectrum (ESI+): m/z = 552 [M+H]+
(151) 1-(2-{3-[(methylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-l-yl)-xanthine Rf value: 0.55 (silica gel, methylene chloride/methanol/ triethylamine =
80:20:0.1) Mass spectrum (ESI+): m/z = 538 [M+H]+
(152) 1-(2-{3-[(aminocarbonyl) methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 524 [M+H]+
(153) 1-(2-{2-[bis(methanesulphonyl)-amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-l-yl)-xanthine Mass spectrum (ESI+): m/z = 622 [M+H]+
(154) 1-methyl-3-[2-(4-methoxy-phenyl)-ethyl]-7-(2-cyano-benzyl)-8-(3-amino p" piperidin-1-yl)-xanthine Rf value: 0.35 (silica gel, methylene chloride/methanol = 9:1) Mass spectrum (ESI+): m/z = 514 [M+H]+
(155) 1-methyl-3-(2-phenyl-ethyl)-7-(2-cyano-benzyl)-8-(3-amino-piperidin-l-yl)-xanthine Mass spectrum (ESI+): m/z = 484 [M+H]+
(156) 1-(2-{3-[(aminocarbonyl)amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 509 [M+H]+
(157) 1-(2-{3-[(dimethylaminocarbonyl)amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-l-yl)-xanthine Mass spectrum (ESI+): m/z = 537 [M+H]+
(158) 1-methyl-3-((E)-2-phenyl-vinyl)-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.49 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): rn/z = 435 [M+H]+
(159) 1-(4-oxo-4H-chromen-3-yl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine x trifluoroacetic acid Mass spectrum (ESI+): m/z = 477 [M+H]+
(160) 1-[(3-methyl-pyridin-2-yl)methyl]-3-methyl-7-(3-methyl-2-buten-l -yl)-8-(3-amino-piperidin-1-yl)-xanthine Carried out with isopropanolic hydrochloric acid (5-6 M) in methylene chloride.
Rf value: 0.54 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 438 [M+H]+
(161) 1-[(5-methyl-pyridin-2-yl)methyl]-3-methyl-7-(3-methyl-2-buten-l -yl)-8-(3-amino-piperidin-1-yl)-xanthine Carried out with isopropanolic hydrochloric acid (5-6 M) in methylene chloride.
Rf value: 0.35 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 438 [M+H]+
(162) 1-[(4-methyl-pyridin-2-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yi)-xanthine Carried out with isopropanolic hydrochloric acid (5-6 M) in methylene chloride.
Rf value: 0.39 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 438 [M+H]+
(163) 1-[(quinolin-4-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidi n-1-yl)-xanthine Carried out with isopropanolic hydrochloric acid (5-6 M) in methylene chloride.
Rf value: 0.53 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 474 [M+H]+
(164) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-(endo-6-amino-2-aza-bicyclo[2.2.2]oct-2-yl)-xanthi ne Carried out with isopropanolic hydrochloric acid (5-6 M) in methylene chloride.
Melting point: 174-179 C
Mass spectrum (ESI+): m/z = 373 [M+H]+
(165) 1-[(quinolin-8-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Carried out with isopropanolic hydrochloric acid (5-6 M) in methylene chloride.
Melting point: 175-177 C
Mass spectrum (ESI+): m/z = 474 [M+H]+
(166) 1-[(5-nitro-isoquinolin-1-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Carried out with isopropanolic hydrochloric acid (5-6 M) in methylene chloride.
Rf value: 0.47 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 519 [M+H]+
(167) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-(exo-6-amino-2-aza-bicyclo[2.2.2]oct-2-yl)-xanthine Carried out with isopropanolic hydrochloric acid (5-6 M) in methylene chloride.
Rf value: 0.23 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
95:5:0.1) Mass spectrum (ESI+): m/z = 373 [M+H]+
(168) 1-[(2-oxo-l,2-dihydro-quinolin-4-yl)methylj-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Carried out with isopropanolic hydrochloric acid (5-6 M) in methylene chloride.
Rf value: 0.43 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 490 [M+H]+
(169) 1-[(5-amino-isoquinolin-1-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Carried out with isopropanolic hydrochloric acid (5-6 M) in methylene chloride.
Rf value: 0.39 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 489 [M+H]+
(170) 1-[2-(3-cyano-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yi)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.65 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 476 [M+H]+
(171) 1-[2-(3-aminosulphonyl-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-l -yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.24 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 530 [M+H]+
(172) 1-[2-(3-aminocarbonyl-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.10 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI'): m/z = 494 [M+H]+
(173) 1-(2-phenoxy-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-l -yl)-xanthine Mass spectrum (ESI+): m/z = 453 [M+H]+
(174) 1,3-dimethyl-2-thioxo-7-benzyl-8-(3-amino-piperidin-l-yl)-xanthine x trifluoroacetic acid Rf value: 0.50 (aluminium oxide, methylene chloride/methanol = 20:1) Mass spectrum (ESI+): m/z = 385 [M+H]+

Example 3 1.3-dimethyl-7-(3-methyl-2-buten-1-y1)-8-(3-methylamino-piperidin-1-vi)-xanthine 154 mg of 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine and 0.032 ml of aqueous formaldehyde solution (37 % by weight) in 0.5 ml of methanol are combined with 24 mg of sodium borohydride and stirred at ambient temperature.
0.01 ml of formaldehyde solution and 10 mg of sodium borohydride are both added twice more and stirring is continued at ambient temperature. The reaction mixture is combined with 1 M sodium hydroxide solution and repeatedly extracted with ethyl acetate. The organic phases are combined, dried and evaporated down. The residue is purified by chromatography over an aluminium oxide column with ethyl acetate/methanol.
Yield: 160 mg (25% of theory) Mass spectrum (ESI+): m/z = 361 [M+H]+
Rf value: 0.80 (aluminium oxide, ethyl acetate/methanol = 4:1) The following compound is obtained analogously to Example 3:

(1) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-(3-dimethylamino-piperidin-l -yl)-xanthine Mass spectrum (ESI+): m/z = 375 [M+H]+
Rf value: 0.65 (aluminium oxide, methylene chloride/methanol = 100:1) Example 4 (S)-1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-{3-[(2-cyanpyrrolidin-1-ylcarbonyl-methvl)aminol-piperidin-1-vl)-xanthine Prepared by reacting the compound of Example 1(4) with (S)-1 -(bromoacetyl)-2-cyano-pyrrolidine in tetrahydrofuran in the presence of triethylamine at ambient temperature Melting point: 67-68 C
Mass spectrum (ESI+): m/z = 505 [M+Na]+
Example 5 1-methvl-7-benzyl-8-(3-amino-12iperidin-1-yl)-xanthine Prepared by treating 1-methyl-3-(2-trimethylsilanyl-ethoxymethyl)-7-benzyl-8-(3-amino-piperidin-l-yl)-xanthine with trifluoroacetic acid in methylene chloride at ambient temperature Mass spectrum (ESI+): m/z = 355 [M+H]+
Example 6 1-methyl-3-carboxymethyl-7-benzyl-8-l3-amino-piperidin-1-yl)-xanthine Prepared by treating 1 -methyl-3-[(methoxycarbonyl)-methyl]-7-benzyl-8-(3-amino-piperidin-1 -yl)-xanthine with 1 N sodium hydroxide solution in methanol Melting point: 212-215 C
Mass spectrum (ESI+): m/z = 413 [M+H]+

The following compounds are obtained analogously to Example 6:

(1) 1-carboxymethyl-3-methyl-7-(3-methyl-2-buten-1-yl)-8-((S)-3-amino-piperidin-l -yl)-xanthine Rf value: 0.54 (ready-made reversed phase TLC plate(E. Merck), acetonitrile/water/
trifluoroacetic acid = 50:50:1) Mass spectrum (ESI+): m/z = 391 [M+H]+

(2) 1-(3-carboxy-propyl)-3-methyl-7-(3-methyl-2-buten-1 -yl)-8-((S)-3-amino-piperidin-1 -yl)-xanthine Rf value: 0.42 (ready-made reversed phase TLC plate(E. Merck), acetonitrile/water/
trifluoroacetic acid = 50:50:1) Mass spectrum (ESI+): m/z = 419 [M+H]+

(3) 1-[2-(4-carboxy-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1 -yl)-8-((S)-3-amino-piperidin-1 -yl)-xanthine A"""" Rf value: 0.42 (ready-made reversed phase TLC plate(E. Merck), acetonitrile/water/
trifluoroacetic acid = 50:50:1) Mass spectrum (ESI+): m/z = 481 [M+H]+

(4) 1-(2-carboxy-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine Melting point: 226-228 C
Mass spectrum (ESI+): m/z = 405 [M+H]+

(5) 1-(2-phenyl-ethyl)-3-carboxymethyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine ep""^ Melting point: 228-235 C
Mass spectrum (ESI+): m/z = 481 [M+H]+
Example 7 1-[2-(3-amino-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-vl)-xanthine Prepared by reduction of 1-[2-(3-nitro-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-l-yl)-8-(3-amino-piperidin-1-yl)-xanthine with iron in a mixture of ethanol, water and glacial acetic acid (10:5:1).
Rf value: 0.45 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
9:1:0.1) Mass spectrum (ESI+): m/z = 452 [M+H]+

The following compounds are obtained analogously to Example 7:

(1) 1-[2-(2-amino-phenyl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.20 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
9:1:0.1) Mass spectrum (ESI+): m/z = 452 [M+H]+

(2) 1,3-dimethyl-7-(3-amino-benzyl)-8-(3-amino-piperidin-1-yl)-xanthine Rf value: 0.20 (silica gel, methylene chloride/methanol/conc. aqueous ammonia =
90:10:1) Mass spectrum (ESI+): m/z = 384 [M+H]+

(3) 1,3-dimethyl-7-(2-amino-benzyl)-8-(3-amino-piperidin-1-yl)-xanthine Mass spectrum (ESI+): m/z = 384 [M+H]+

Example 8 1.3-dimethyl-7-(3-methyl-2-buten-1-vl)-8-(1-amino-12iperidin-4-vl)-xanthine Prepared by treating 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-(1-nitroso-piperidin-4-yl)-xanthine with zinc in a mixture of acetic acid and water (1:1.5) at 80 C
Mass spectrum (ESI+): rr/z = 347 [M+H]+

The following compounds are obtained analogously to Example 8:

(1) 1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-(1-amino-piperidin-3-yl)-xanthine Mass spectrum (ESI+): m/z = 347 [M+H]+

Example 9 1-(2-hydroxyimino-2-phenyl-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-((R)-3-amino piperidin-1-vi)-xanthine Prepared by reacting 1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine with hydroxylamine-hydrochloride in the presence of potassium carbonate in ethanol at 85 C.
Rf value: 0.54 (ready-made reversed phase TLC plate(E. Merck), acetonitrile/water/
trifluoroacetic acid = 10:10:0.2) Mass spectrum (ESI+): m/z = 466 [M+H]+
Example 10 1-[2-(2-methanesulphonylamino-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yll)-xanthine Prepared by treating 1-(2-{2-[bis(methanesulphonyl)-amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine with 5 N
sodium hydroxide solution in tetrahydrofuran at ambient temperature.
Mass spectrum (ESI+): m/z = 544 [M+H]+

The following compounds may also be obtained analogously to the foregoing Examples and other methods known from the literature:

(1) 7-(3-methyl-2-buten-1 -yl)-8-(3-amino-piperidin-1 -yl)-xanthine (2) 1-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine (3) 3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine (4) 1 -ethyl -3-methyl -7-(3- methyl-2-buten- 1 -yl) -8-(3-ami no-pi pe rid in-1 -yl)-xanthi ne (5) 1 -propyl-3-methyl-7-(3-methyl-2-buten- 1 -yl)-8-(3-ami no-piperi din- 1 -yl)-xanthine (6) 1-(2-propyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yi)-xanthine (7) 1-butyl-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-l -yl)-xanthine (8) 1-(2-butyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine (9) 1-(2-methylpropyl)-3-methyl-7-(3-methyl-2-buten-1-yi)-8-(3-amino-piperidin-l -yl)-xanthine (10) 1-(2-propen-1-yi)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine (11) 1-(2-propyn-1-yi)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine (12) 1-cyclopropylmethyl-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-l -yl)-xanthine (13) 1-benzyl-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine (14) 1-(2-phenylethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-l -yl)-xanthine (15) 1-(2-hydroxyethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine (16) 1-(2-methoxyethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-l -yl)-xanthine (17) 1-(2-ethoxyethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1 -yl)-xanthine DEMANDES OU BREVETS VOLUMINEUX
LA PRESENTE PARTIE DE CETTE DEMANDE OU CE BREVETS
COMPREND PLUS D'UN TOME.

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Claims (26)

CLAIMS:
1. A compound of formula a tautomer, enantiomer, diastereomer, mixture thereof or a salt thereof, wherein R1 denotes a hydrogen atom, a C1-6-alkyl group, a C3-6-alkenyl group, a C3-4-alkenyl group which is substituted by a C1-2-alkyloxy-carbonyl group, a C3-6-alkynyl group, a C3-6-cycloalkyl-C1-3-alkyl group, a phenyl group which may be substituted by a fluorine, chlorine or bromine atom or by a methyl, trifluoromethyl, hydroxy or methoxy group, a phenyl-C1-4-alkyl group wherein the phenyl moiety is substituted by R10 to R12, wherein R10 denotes a hydrogen atom, a fluorine, chlorine or bromine atom, a C1-4-alkyl, trifluoromethyl, hydroxymethyl, C3-6-cycloalkyl, ethynyl or phenyl group, a hydroxy, C1-4-alkyloxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, phenoxy, benzyloxy, 2-propen-1-yloxy, 2-propyn-1-yloxy, cyano-C1-2-alkyloxy, C1-2-alkylsulphonyloxy, phenylsulphonyloxy, carboxy-C1-3-alkyloxy, C1-3-alkyloxy-carbonyl-C1-3-alkyloxy, aminocarbonyl-C1-3-alkyloxy, C1-2-alkyl-aminocarbonyl-C1-3-alkyloxy, di-(C1-2-alkyl)aminocarbonyl-C1-3-alkyloxy, pyrrolidin-1-yl-carbonyl-C1-3-alkyloxy, piperidin-1-ylcarbonyl-C1-3-alkyloxy, morpholin-4-ylcarbonyl-C1-3-alkyloxy, methylsulphanylmethoxy, methylsulphinylmethoxy, methylsulphonylmethoxy, C3-6-cycloalkyloxy or C3-6-cycloalkyl-C1-2-alkyloxy group, a carboxy, C1-3-alkyloxycarbonyl, carboxy-C1-3-alkyl, C1-3-alkyloxy-carbonyl-C1-3-alkyl, aminocarbonyl, C1-2-alkylaminocarbonyl, di-(C1-2-alkyl)aminocarbonyl, morpholin-4-ylcarbonyl or cyano group, a nitro, amino, C1-2-alkylamino, di-(C1-2-alkyl)amino, cyano-C1-2-alkylamino, [N-(cyano-C1-2-alkyl)-N-C1-2-alkyl-amino], C1-2-alkyloxy-carbonyl-C1-2-alkylamino, C1-2-alkyl-carbonylamino, C1-2-alkyloxy-carbonylamino, C1-3-alkylsulphonylamino, bis-(C1-2-alkylsulphonyl)-amino, aminosulphonylamino, C1-2-alkylamino-sulphonylamino, di-(C1-2-alkyl)amino-sulphonylamino, morpholin-4-yl-sulphonylamino, (C1-2-alkylamino)thiocarbonylamino, (C1-2-alkyloxy-carbonylamino)carbonylamino, aminocarbonylamino, C1-2-alkylaminocarbonylamino, di-(C1-2-alkyl)aminocarbonylamino or morpholin-4-ylcarbonylamino group, a 2-oxo-imidazolidin-1-yl, 3-methyl-2-oxo-imidazolidin-1-yl, 2,4-dioxo-imidazolidin-1-yl, 3-methyl-2,4-dioxo-imidazolidin-1-yl, 2,5-dioxo-imidazolidin-1-yl, 3-methyl-2,5-dioxo-imidazolidin-1-yl, 2-oxo-hexahydropyrimidin-1-yl or 3-methyl-2-oxo-hexahydropyrimidin-1-yl group, or a C1-2-alkylsulphanyl, C1-2-alkylsulphinyl, C1-2-alkylsulphonyl, aminosulphonyl, C1-2-alkylaminosulphonyl or di-(C1-2-alkyl)aminosulphonyl group, and R11 and R12, which may be identical or different, denote a hydrogen, fluorine, chlorine or bromine atom or a methyl, cyano, trifluoromethyl or methoxy group, or, R11 together with R12, if they are bound to adjacent carbon atoms, also denote a methylenedioxy, difluoromethylenedioxy, 1,3-propylene or 1,4-butylene group, a phenyl-C1-3-alkyl group wherein the alkyl moiety is substituted by a carboxy, C1-2-alkyloxy-carbonyl, aminocarbonyl, C1-2-alkylaminocarbonyl or di-(C1-2-alkyl)aminocarbonyl group, a phenyl-C2-3-alkenyl group, wherein the phenyl moiety may be substituted by a fluorine, chlorine or bromine atom or by a methyl, trifluoromethyl or methoxy group, a phenyl-(CH2)m-A-(CH2)n group wherein the phenyl moiety is substituted by R10 to R12, wherein R10 to R12 are as hereinbefore defined and A denotes a carbonyl, hydroxyiminomethylene or C1-2-alkyloxyiminomethylene group, m denotes the number 0 or 1 and n denotes the number 1 or 2, a phenylcarbonylmethyl group wherein the phenyl moiety is substituted by R10 to R12, wherein R10 to R12 are as hereinbefore defined and the methyl moiety is substituted by a methyl or ethyl group, a phenylcarbonylmethyl group wherein two adjacent hydrogen atoms of the phenyl moiety are replaced by a -O-CO-NH, -NH-CO-NH, -N=CH-NH, -N=CH-O or -O-CH2-CO-NH- bridge, wherein the abovementioned bridges may be substituted by one or two methyl groups, a phenyl-(CH2)m-B-(CH2)n group wherein the phenyl moiety is substituted by R10 to R12, wherein R10 to R12, m and n are as hereinbefore defined and B denotes a methylene group which is substituted by a hydroxy or C1-2-alkyloxy group and is optionally additionally substituted by a methyl group, a naphthylmethyl or naphthylethyl group, wherein the naphthyl moiety is substituted in each case by R10 to R12, wherein R10 to R12 are as hereinbefore defined, a [1,4]naphthoquinon-2-yl, chromen-4-on-3-yl or 1-oxoindan-2-yl group, a heteroaryl-C1-3-alkyl group, wherein by the term heteroaryl is meant a pyrrolyl, furanyl, thienyl, pyridyl, indolyl, benzofuranyl, benzothiophenyl, quinolinyl or isoquinolinyl group, or a pyrrolyl, furanyl, thienyl or pyridyl group wherein one or two methyne groups are replaced by nitrogen atoms, or an indolyl, benzofuranyl, benzothiophenyl, quinolinyl or isoquinolinyl group wherein one to three methyne groups are replaced by nitrogen atoms, or a 1,2-dihydro-2-oxo-pyridinyl, 1,4-dihydro-4-oxo-pyridinyl, 2,3-dihydro-3-oxo-pyridazinyl, 1,2,3,6-tetrahydro-3,6-dioxo-pyridazinyl, 1,2-dihydro-2-oxo-pyrimidinyl, 3,4-dihydro-4-oxo-pyrimidinyl, 1,2,3,4-tetrahydro-2,4-dioxo-pyrimidinyl, 1,2-dihydro-2-oxo-pyrazinyl, 1,2,3,4-tetrahydro-2,3-dioxo-pyrazinyl, 2,3-dihydro-2-oxo-indolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydro-2-oxo-1 H-benzimidazolyl, 2,3-dihydro-2-oxo-benzoxazolyl, 1,2-dihydro-2-oxo-quinolinyl, 1,4-dihydro-4-oxo-quinolinyl, 1,2-dihydro-1-oxo-isoquinolinyl, 1,4-dihydro-4-oxo-cinnolinyl, 1,2-dihydro-2-oxo-quinazolinyl, 1,4-dihydro-4-oxo-quinazolinyl, 1,2,3,4-tetrahydro-2,4-dioxo-quinazolinyl, 1,2-dihydro-2-oxoquinoxalinyl, 1,2,3,4-tetrahydro-2,3-dioxo-quinoxalinyl, 1,2-dihydro-1-oxo-phthalazinyl, 1,2,3,4-tetrahydro-1,4-dioxo-phthalazinyl, chromanyl, cumarinyl, 2,3-dihydro-benzo[1,4]dioxinyl or 3,4-dihydro-3-oxo-2H-benzo[1,4]oxazinyl group, wherein the abovementioned heteroaryl groups may be substituted by R10 to R12, wherein R10 to R12 are as hereinbefore defined, a furanyl-A-CH2, thienyl-A-CH2, thiazolyl-A-CH2 or pyridyl-A-CH2 group, wherein A
is as hereinbefore defined, a furanyl-B-CH2, thienyl-B-CH2, thiazolyl-B-CH2 or pyridyl-B-CH2 group, wherein B
is as hereinbefore defined, a C1-4-alkyl-A-(CH2)n group, wherein A and n are as hereinbefore defined, a C3-6-cycloalkyl-(CH2)m-A-(CH2)n group, wherein A, m and n are as hereinbefore defined, a C3-6-cycloalkyl-(CH2)m-B-(CH2), group, wherein B, m and n are as hereinbefore defined, a R21-A-(CH2)n group wherein R21 denotes a C1-2-alkyloxycarbonyl, aminocarbonyl, C1-2-alkylaminocarbonyl, di-(C1-2-alkyl)aminocarbonyl, pyrrolidin-1-yl-carbonyl, piperidin-1-yl-carbonyl or morpholin-4-yl-carbonyl group and A
and n are as hereinbefore defined, a phenyl-D-C1-3-alkyl group wherein the phenyl moiety is optionally substituted by a fluorine, chlorine or bromine atom, a methyl, trifluoromethyl or methoxy group and D denotes an oxygen or sulphur atom, a sulphinyl or sulphonyl group, a C1-4-alkyl group substituted by a group R a, wherein R a denotes a cyano, carboxy, C1-3-alkyloxy-carbonyl, aminocarbonyl, C1-2-alkyl-aminocarbonyl, di-(C1-2-alkyl)aminocarbonyl, pyrrolidin-1-yl-carbonyl, piperidin-1-ylcarbonyl or morpholin-4-ylcarbonyl group, a C2-4-alkyl group substituted by a group R b, wherein R b denotes a hydroxy, C1-3-alkyloxy, amino, C1-3-alkylamino, di-(C1-3-alkyl)-amino, pyrrolidin-1-yl, piperidin-1-yl, morpholin-4-yl, piperazin-1-yl, 4-methyl-piperazin-1-yl or 4-ethyl-piperazin-1-yl group and is isolated from the cyclic nitrogen atom in the 1 position of the xanthine skeleton by at least two carbon atoms, or an amino or benzoylamino group, R2 denotes a hydrogen atom, a C1-6-alkyl group, a C2-4-alkenyl group, a C3-4-alkynyl group, a C3-6-cycloalkyl group, a C3-6-cycloalkyl-C1-3-alkyl group, a tetra hydrofuran-3-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, tetrahydrofuranylmethyl or tetrahydropyranylmethyl group, a phenyl group which is optionally substituted by a fluorine, chlorine or bromine atom or by a methyl, trifluoromethyl, hydroxy, methoxy, difluoromethoxy or trifluoromethoxy group, a phenyl-C1-4-alkyl group wherein the phenyl moiety is optionally substituted by a fluorine, chlorine or bromine atom, a methyl, trifluoromethyl, dimethylamino, hydroxy, methoxy, difluoromethoxy or trifluoromethoxy group, a phenyl-C2-3-alkenyl group, wherein the phenyl moiety may be substituted by a fluorine, chlorine or bromine atom or by a methyl, trifluoromethyl or methoxy group, a phenylcarbonyl-C1-2-alkyl group wherein the phenyl moiety is optionally substituted by a fluorine, chlorine or bromine atom, a methyl, trifluoromethyl, hydroxy, methoxy, difluoromethoxy or trifluoromethoxy group, a heteroaryl-C1-3-alkyl group, wherein the term heteroaryl is as hereinbefore defined, a furanylcarbonylmethyl, thienylcarbonylmethyl, thiazolylcarbonylmethyl or pyridylcarbonylmethyl group, a C1-4-alkyl-carbonyl-C1-2-alkyl group, a C3-6-cycloalkyl-carbonyl-C1-2-alkyl group, a phenyl-D-C1-3-alkyl group wherein the phenyl moiety is optionally substituted by a fluorine, chlorine or bromine atom, a methyl, trifluoromethyl, hydroxy, methoxy, difluoromethoxy or trifluoromethoxy group, and D is as hereinbefore defined, or a C1-4-alkyl group substituted by a group R a, wherein R a is as hereinbefore defined, or a C2-4-alkyl group substituted by a group R b, wherein R b is as hereinbefore defined and is isolated from the cyclic nitrogen atom in the 3 position of the xanthine skeleton by at least two carbon atoms, R3 denotes a C1-3-alkyl group substituted by the group R c, wherein R c denotes a C3-7-cycloalkyl group optionally substituted by one or two C1-3-alkyl groups, a C5-7-cycloalkenyl group optionally substituted by one or two C1-3-alkyl groups or an aryl group or a furanyl, thienyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyridyl, pyridazinyl, pyrimidyl or pyrazinyl group, wherein the abovementioned heterocyclic groups may each be substituted by one or two C1-3-alkyl groups or by a fluorine, chlorine, bromine or iodine atom or by a trifluoromethyl, cyano or C1-3-alkyloxy group, a C3-8-alkenyl group, a C3-6-alkenyl group substituted by a fluorine, chlorine or bromine atom, or a trifluoromethyl group, a C3-8-alkynyl group, an aryl group or an aryl-C2-4-alkenyl group, and R4 denotes an azetidin-1-yl or pyrrolidin-1-yl group which is substituted in the 3 position by an R e NR d group and may additionally be substituted by one or two C1-3-alkyl groups, wherein R e denotes a hydrogen atom or a C1-3-alkyl group and R d denotes a hydrogen atom or a C1-3-alkyl group, or a piperidin-1-yl or hexahydroazepin-1-yl group which is substituted in the 3 position by an R e NR d group and may additionally be substituted by one or two C1-3-alkyl groups, wherein R e and R d are as hereinbefore defined, while by the aryl groups mentioned in the definition of the groups mentioned above are meant phenyl or naphthyl groups which may be mono- or disubstituted independently of one another by R h, while the substituents may be identical or different and R h denotes a fluorine, chlorine, bromine or iodine atom, a trifluoromethyl, cyano, nitro, amino, C1-3-alkyl, cyclopropyl, ethenyl, ethynyl, hydroxy, C1-3-alkyloxy, difluoromethoxy or trifluoromethoxy group and unless otherwise stated, the abovementioned alkyl and alkenyl groups may be straight-chained or branched.
2. Compound of formula I according to claim 1, a tautomer, enantiomer, diastereomer, mixture thereof or a salt thereof, wherein R3 and R4 are as defined in claim 1, R1 denotes a hydrogen atom, a C1-6-alkyl group, a C3-6-alkenyl group, a C3-4-alkenyl group which is substituted by a C1-2-alkyloxy-carbonyl group, a C3-6-alkynyl group, a C3-6-cycloalkyl-C1-3-alkyl group, a phenyl group which may be substituted by a fluorine, chlorine or bromine atom or by a methyl, trifluoromethyl, hydroxy or methoxy group, a phenyl-C1-4-alkyl group wherein the phenyl moiety is substituted by R10 to R12, wherein R10 denotes a hydrogen atom, a fluorine, chlorine or bromine atom, a C1-4-alkyl, trifluoromethyl, hydroxymethyl, C3-6-cycloalkyl, ethynyl or phenyl group, a hydroxy, C1-4-alkyloxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, phenoxy, benzyloxy, 2-propen-1-yloxy, 2-propyn-1-yloxy, cyano-C1-2-alkyloxy, C1-2-alkylsulphonyloxy, phenylsulphonyloxy, carboxy-C1-3-alkyloxy, C1-3-alkyloxy-carbonyl-C1-3-alkyloxy, aminocarbonyl-C1-3-alkyloxy, C1-2-alkyl-aminocarbonyl-C1-3-alkyloxy, di-(C1-2-alkyl)aminocarbonyl-C1-3-alkyloxy, pyrrolidin-1-yl-carbonyl-C1-3-alkyloxy, piperidin-1-ylcarbonyl-C1-3-alkyloxy, morpholin-4-ylcarbonyl-C1-3-alkyloxy, methylsulphanylmethoxy, methylsulphinylmethoxy, methylsulphonylmethoxy, C3-6-cycloalkyloxy or C3-6-cycloalkyl-C1-2-alkyloxy group, a carboxy, C1-3-alkyloxycarbonyl, carboxy-C1-3-alkyl, C1-3-alkyloxy-carbonyl-C1-3-alkyl, aminocarbonyl, C1-2-alkylaminocarbonyl, di-(C1-2-alkyl)aminocarbonyl, morpholin-4-ylcarbonyl or cyano group, a nitro, amino, C1-2-alkylamino, di-(C1-2-alkyl)amino, cyano-C1-2-alkylamino, [N-(cyano-C1-2-alkyl)-N-C1-2-alkyl-amino], C1-2-alkyloxy-carbonyl-C1-2-alkylamino, C1-2-alkyl-carbonylamino, C1-2-alkyloxy-carbonylamino, C1-3-alkylsulphonylamino, bis-(C1-2-alkylsulphonyl)-amino, aminosulphonylamino, C1-2-alkylamino-sulphonylamino, di-(C1-2-alkyl)amino-sulphonylamino, morpholin-4-yl-sulphonylamino, (C1-2-alkylamino)thiocarbonylamino, (C1-2-alkyloxy-carbonylamino)carbonylamino, aminocarbonylamino, C1-2-alkylaminocarbonylamino, di-(C1-2-alkyl)aminocarbonylamino or morpholin-4-ylcarbonylamino group, a 2-oxo-imidazolidin-1-yl, 3-methyl-2-oxo-imidazolidin-1-yl, 2,4-dioxo-imidazolidin-1-yl, 3-methyl-2,4-dioxo-imidazolidin-1-yl, 2, 5-dioxo-imidazolidin-1-yl, 3-methyl-2,5-dioxo-imidazolidin-1-yl, 2-oxo-hexahydropyrimidin-1-yl or 3-methyl-2-oxo-hexahydropyrimidin-1-yl group, or a C1-2-alkylsulphanyl, C1-2-alkylsulphinyl, C1-2-alkylsulphonyl, aminosulphonyl, C1-2-alkylaminosulphonyl or di-(C1-2-alkyl)aminosulphonyl group, and R11 and R12, which may be identical or different, denote a hydrogen, fluorine, chlorine or bromine atom or a methyl, cyano, trifluoromethyl or methoxy group, or, R11 together with R12, if they are bound to adjacent carbon atoms, also denote a methylenedioxy, difluoromethylenedioxy, 1,3-propylene or 1,4-butylene group, a phenyl-C1-3-alkyl group wherein the alkyl moiety is substituted by a carboxy, C1-2-alkyloxy-carbonyl, aminocarbonyl, C1-2-alkylaminocarbonyl or di-(C1-2-alkyl)aminocarbonyl group, a phenyl-C2-3-alkenyl group, wherein the phenyl moiety may be substituted by a fluorine, chlorine or bromine atom or by a methyl, trifluoromethyl or methoxy group, a phenyl-(CH2)-A-(CH2)n group wherein the phenyl moiety is substituted by R10 to R12, wherein R10 to R12 are as hereinbefore defined and A denotes a carbonyl, hydroxyiminomethylene or C1-2-alkyloxyiminomethylene group, m denotes the number 0 or 1 and n denotes the number 1 or 2, a phenylcarbonylmethyl group wherein the phenyl moiety is substituted by R10 to R12, wherein R10 to R12 are as hereinbefore defined and the methyl moiety is substituted by a methyl or ethyl group, a phenylcarbonylmethyl group wherein two adjacent hydrogen atoms of the phenyl moiety are replaced by a -O-CO-NH, -NH-CO-NH, -N=CH-NH, -N=CH-O or -O-CH2-CO-NH- bridge, wherein the abovementioned bridges may be substituted by one or two methyl groups, a phenyl-(CH2)m-B-(CH2)n group wherein the phenyl moiety is substituted by R10 to R12, wherein R10 to R12, m and n are as hereinbefore defined and B denotes a methylene group which is substituted by a hydroxy or C1-2-alkyloxy group and is optionally additionally substituted by a methyl group, a naphthylmethyl or naphthylethyl group, wherein the naphthyl moiety is substituted in each case by R10 to R12, wherein R10 to R12 are as hereinbefore defined, a [1,4]naphthoquinon-2-yl, chromen-4-on-3-yl or 1-oxoindan-2-yl group, a heteroaryl-C1-3-alkyl group, wherein the term heteroaryl denotes a pyrrolyl, imidazolyl, triazolyl, furanyl, thienyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, benzimidazolyl, 2,3-dihydro-2-oxo-1H-benzimidazolyl, indazolyl, benzofuranyl, 2,3-dihydrobenzofuranyl, benzoxazolyl, 2,3-dihydro-2-oxo-benzoxazolyl, benzoisoxazolyl, benzothiophenyl, benzothiazolyl, benzoisothiazolyl, quinolinyl, 1,2-dihydro-2-oxo-quinolinyl, isoquinolinyl, 1,2-dihydro-1-oxo-isoquinolinyl, cinnolinyl, quinazolinyl, 1,2-dihydro-2-oxo-quinazolinyl, 1,2-dihydro-1-oxo-phthalazin-4-yl, cumarinyl or 3,4-dihydro-3-oxo-2H-benzo[1,4]oxazinyl group, wherein the abovementioned heteroaryl groups may be substituted at carbon atoms by a fluorine, chlorine or bromine atom, by a methyl, trifluoromethyl, cyano, aminocarbonyl, aminosulphonyl, methylsulphonyl, nitro, amino, acetylamino, methylsulphonylamino, methoxy, difluoromethoxy or trifluoromethoxy group and the imino groups of the abovementioned heteroaryl groups may be substituted by methyl or ethyl groups, a furanyl-A-CH2, thienyl-A-CH2, thiazolyl-A-CH2 or pyridyl-A-CH2 group, wherein A
is as hereinbefore defined, a furanyl-B-CH2, thienyl-B-CH2, thiazolyl-B-CH2 or pyridyl-B-CH2 group, wherein B
is as hereinbefore defined, a C1-4-alkyl-A-(CH2)n group, wherein A and n are as hereinbefore defined, a C3-6-cycloalkyl-(CH2)m-A-(CH2)n group, wherein A, m and n are as hereinbefore defined, a C3-6-cycloalkyl-(CH2)m-B-(CH2)n group, wherein B, m and n are as hereinbefore defined, a R21-A-(CH2)n group wherein R21 denotes a C1-2-alkyloxycarbonyl, aminocarbonyl, C1-2-alkylaminocarbonyl, di-(C1-2-alkyl)aminocarbonyl, pyrrolidin-1-yl-carbonyl, piperidin-1-yl-carbonyl or morpholin-4-yl-carbonyl group and A
and n are as hereinbefore defined, a phenyl-D-C1-3-alkyl group wherein the phenyl moiety is optionally substituted by a fluorine, chlorine or bromine atom, a methyl, trifluoromethyl or methoxy group and D denotes an oxygen or sulphur atom, a sulphinyl or sulphonyl group, a C1-4-alkyl group substituted by a group R a, wherein R a denotes a cyano, carboxy, C1-3-alkyloxy-carbonyl, aminocarbonyl, C1-2-alkyl-aminocarbonyl, di-(C1-2-alkyl)aminocarbonyl, pyrrolidin-1-yl-carbonyl, piperidin-1-ylcarbonyl or morpholin-4-ylcarbonyl group, a C2-4-alkyl group substituted by a group R b, wherein R b denotes a hydroxy, C1-3-alkyloxy, amino, C1-3-alkylamino, di-(C1-3-alkyl)-amino, pyrrolidin-1-yl, piperidin-1-yl, morpholin-4-yl, piperazin-1-yl, 4-methyl-piperazin-1-yl or 4-ethyl-piperazin-1-yl group and is isolated from the cyclic nitrogen atom in the 1 position of the xanthine skeleton by at least two carbon atoms, or an amino or benzoylamino group, R 2 denotes a hydrogen atom, a C1-6-alkyl group, a C2-4-alkenyl group, a C3-4-alkynyl group, a C3-6-cycloalkyl group, a C3-6-cycloalkyl-C1-3-alkyl group, a tetrahydrofuran-3-yl, tetra hydropyran-3-yl, tetra hydropyran-4-yl, tetrahydrofuranyl methyl or tetrahydropyranylmethyl group, a phenyl group which is optionally substituted by a fluorine, chlorine or bromine atom or by a methyl, trifluoromethyl, hydroxy, methoxy, difluoromethoxy or trifluoromethoxy group, a phenyl-C1-4-alkyl group wherein the phenyl moiety is optionally substituted by a fluorine, chlorine or bromine atom, a methyl, trifluoromethyl, dimethylamino, hydroxy, methoxy, difluoromethoxy or trifluoromethoxy group, a phenyl-C2-3-alkenyl group, wherein the phenyl moiety may be substituted by a fluorine, chlorine or bromine atom or by a methyl, trifluoromethyl or methoxy group, a phenylcarbonyl-C1-2-alkyl group wherein the phenyl moiety is optionally substituted by a fluorine, chlorine or bromine atom, a methyl, trifluoromethyl, hydroxy, methoxy, difluoromethoxy or trifluoromethoxy group, a heteroaryl-C1-3-alkyl group, wherein the term heteroaryl is as hereinbefore defined, a furanylcarbonyimethyl, thienylcarbonylmethyl, thiazolylcarbonylmethyl or pyridylcarbonylmethyl group, a C1-4-alkyl-carbonyl-C1-2-alkyl group, a C3-6-cycloalkyl-carbonyl-C1-2-alkyl group, a phenyl-D-C1-3-alkyl group wherein the phenyl moiety is optionally substituted by a fluorine, chlorine or bromine atom, a methyl, trifluoromethyl, hydroxy, methoxy, difluoromethoxy or trifluoromethoxy group, and D is as hereinbefore defined, or a C1-4-alkyl group substituted by a group R a, wherein R a is as hereinbefore defined, or a C2-4-alkyl group substituted by a group R b, wherein R b is as hereinbefore defined and is isolated from the cyclic nitrogen atom in the 3 position of the xanthine skeleton by at least two carbon atoms, while by the aryl groups mentioned in the definition of the groups mentioned above are meant phenyl or naphthyl groups which may be mono- or disubstituted independently of one another by R h, while the substituents may be identical or different and R h denotes a fluorine, chlorine, bromine or iodine atom, a trifluoromethyl, cyano, nitro, amino, C1-3-alkyl, cyclopropyl, ethenyl, ethynyl, hydroxy, C1-3-alkyloxy, difluoromethoxy or trifluoromethoxy group and unless otherwise stated, the abovementioned alkyl and alkenyl groups may be straight-chained or branched.
3. Compound of formula I according to claim 1 or 2, a tautomer, enantiomer, diastereomer, mixture thereof or a salt thereof, wherein R1 denotes a hydrogen atom, a C1-4-alkyl group, a C3-5-alkenyl group, a 2-propen-1-yl group which is substituted by a methoxycarbonyl group, a C3-5-alkynyl group, a phenyl-C1-4-alkyl group wherein the phenyl moiety is substituted by R10 to R12, wherein R10 denotes a hydrogen atom, a fluorine, chlorine or bromine atom, a methyl, ethyl, trifluoromethyl or ethynyl group, a hydroxy, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, phenoxy, benzyloxy, 2-propen-1-yloxy, 2-propyn-1-yloxy, cyano-C1-2-alkyloxy, C1-2-alkyl-sulphonyloxy, phenylsulphonyloxy, carboxy-C1-2-alkyloxy, C1-2-alkyloxy-carbonyl-C1-2-alkyloxy, aminocarbonyl-C1-2-alkyloxy, C1-2-alkyl-aminocarbonyl-C1-2-alkyloxy, di-(C1-2-alkyl)aminocarbonyl-C1-2-alkyloxy, pyrrolidin-1-ylcarbonyl-C1-2-alkyloxy, piperidin-1-ylcarbonyl-C1-2-alkyloxy or morpholin-4-ylcarbonyl-C1-2-alkyloxy group, a carboxy, C1-2-alkyloxy-carbonyl, aminocarbonyl, C1-2-alkylaminocarbonyl, di-(C1-2-alkyl)aminocarbonyl, morpholin-4-ylcarbonyl or cyano group, a nitro, amino, C1-2-alkylamino, di-(C1-2-alkyl)amino, cyano-C1-2-alkylamino, [N-(cyano-C1-2-alkyl)-N-methyl-amino], C1-2-alkyloxy-carbonyl-C1-2-alkylamino, C1-2-alkyl-carbonylamino, C1-2-alkyloxy-carbonylamino, C1-2-alkylsulphonylamino, bis-(C1-2-alkylsulphonyl)-amino, aminosulphonylamino, C1-2-alkylamino-sulphonylamino, di-(C1-2-alkyl)amino-sulphonylamino, morpholin-4-yl-sulphonylamino, (C1-2-alkylamino)thiocarbonylamino, (C1-2-alkyloxy-carbonylamino)carbonylamino, aminocarbonylamino, C1-2-alkylaminocarbonylamino, di-(C1-2-alkyl)aminocarbonylamino or morpholin-4-yl-carbonylamino group, a 2-oxo-imidazolidin-1-yl, 3-methyl-2-oxo-imidazolidin-1-yl, 2,4-dioxo-imidazolidin-1-yl, 3-methyl-2,4-dioxo-imidazolidin-1-yl, 2, 5-dioxo-imidazolidin-1-yl, 3-methyl-2,5-dioxo-imidazolidin-1-yl, 2-oxo-hexahydropyrimidin-1-yl or 3-methyl-2-oxo-hexahydropyrimidin-1-yl group, or a C1-2-alkylsulphanyl, C1-2-alkylsulphinyl, C1-2-alkylsulphonyl, aminosulphonyl, C1-2-alkylaminosulphonyl or di-(C1-2-alkyl)aminosulphonyl group, and R11 and R12, which may be identical or different, denote a hydrogen, fluorine, chlorine or bromine atom or a methyl, cyano or methoxy group, or, R11 together with R12, if they are bound to adjacent carbon atoms, also denote a methylenedioxy group, a phenylmethyl group wherein the methyl moiety is substituted by a carboxy, methoxycarbonyl or aminocarbonyl group, a 2-phenylethyl group wherein the ethyl moiety is substituted by a carboxy, methoxycarbonyl or aminocarbonyl group, a 2-phenylethyl group wherein the ethyl moiety is substituted in the 2 position by a hydroxy, methoxy, hydroxyimino or methoxyimino group, a 2-phenylethyl group wherein the ethyl moiety is substituted in the 2 position by a hydroxy group and a methyl group, a phenylcarbonylmethyl group wherein the phenyl moiety is substituted by R10 to R12, wherein R10 to R12 are as hereinbefore defined, a 1-(phenylcarbonyl)ethyl or 2-(phenylcarbonyl)ethyl group, a 2-phenylethenyl group, a phenylsulphanylmethyl or phenylsulphinylmethyl group, a 2-(phenyloxy)ethyl group, a naphthylmethyl or naphthylethyl group, wherein the naphthyl moiety may be substituted in each case by a methyl, nitro, amino, acetylamino, methylsulphonylamino, cyano, aminocarbonyl or aminosulphonyl group, a[1,4]naphthoquinon-2-yl, chromen-4-on-3-yl or 1-oxoindan-2-yl group an oxazolylmethyl, isoxazolylmethyl, thiazolylmethyl, pyridylmethyl, benzofuranylmethyl, 2,3-dihydrobenzofuranyimethyl, benzo[d]isoxazolylmethyl, benzo[d]isothiazolylmethyl, (1H-indazol-3-yl)methyl, quinolinylmethyl, (1,2-dihydro-2-oxo-quinolin-4-yl)methyl, isoquinolinylmethyl, (1,2-dihydro-1-oxo-isoquinolin-4-yl)methyl, cinnolinylmethyl, quinazolinyimethyl, (1,2-dihydro-2-oxo-quinazolin-yl)methyl, (1,2-dihydro-1-oxo-phthalazin-4-yl)methyl or cumarinylmethyl group, wherein the heterocyclic moiety may be substituted by a methyl group in each case, a quinolinylmethyl or isoquinolinyimethyl group, wherein the heterocyclic moiety is substituted in each case by a cyano, nitro, amino, acetylamino, methylsulphonylamino, aminocarbonyl or aminosulphonyl group, a pyrrolylethyl, triazolylethyl, thienylethyl, thiazolylethyl or pyridylethyl group, wherein the heterocyclic moiety may be substituted in each case by a methyl group, a furanylcarbonylmethyl, thienylcarbonylmethyl, thiazolylcarbonylmethyl or pyridylcarbonylmethyl group, a methyl group which is substituted by a cyclopropyl, cyano, carboxy, aminocarbonyl or methoxycarbonyl group, an ethyl group which is substituted in the 2 position by a hydroxy, methoxy, dimethylamino, carboxy or methoxycarbonyl group, or a propyl group which is substituted in the 3 position by a hydroxy, dimethylamino, carboxy or methoxycarbonyl group, a 2-oxopropyl group or an amino or benzoylamino group, R2 denotes a hydrogen atom, a C1-6-alkyl group, an ethenyl group, a 2-propen-1-yl or 2-propyn-1-yl group, a C3-6-cycloalkyl group, a tetrahydrofuran-3-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, tetrahydrofuranylmethyl or tetrahydropyranylmethyl group, a phenyl group, a phenyl-C1-4-alkyl group, wherein the phenyl moiety may be substituted by a fluorine or chlorine atom, a methyl, dimethylamino, hydroxy, methoxy or trifluoromethoxy group, a phenylcarbonylmethyl group, wherein the phenyl moiety may be substituted by a fluorine or chlorine atom, a hydroxy, methoxy or trifluoromethoxy group, a 2-phenylethenyl group, a 2-(phenyloxy)ethyl group, a pyridylmethyl or pyridylethyl group, a methyl group which is substituted by a C3-6-cycloalkyl, cyano, carboxy or methoxycarbonyl group, or an ethyl group which is substituted in the 2 position by a C3-6-cycloalkyl, cyano, carboxy, methoxycarbonyl, hydroxy, methoxy or dimethylamino group, or a propyl group which is substituted in the 3 position by a C3-6-cycloalkyl, cyano, carboxy, methoxycarbonyl, hydroxy, methoxy or dimethylamino group, R3 denotes a C4-6-alkenyl group, a 1-cyclopenten-1-ylmethyl or 1-cyclohexen-1-ylmethyl group, a 1-cyclopenten-1-ylmethyl group wherein the 1-cyclopenten-1-yl moiety is substituted by a methyl group, a 2-propyn-1-yl, 2-butyn-1-yl or 2-pentyn-1-yl group, a phenyl group which may be substituted by a fluorine atom or a cyano, methyl-methoxy or trifluoromethyl group, a phenyl group which is substituted by two methyl groups, a benzyl group wherein the phenyl moiety may be substituted by one or two fluorine atoms, a chlorine, bromine or iodine atom, or a methyl, methoxy, cyano, nitro or amino group, a furanylmethyl or thienylmethyl group, a cyclopropylmethyl group or a cyclopropylmethyl group wherein the cyclopropyl moiety is substituted by a methyl group, and R4 denotes a piperidin-1-yl group which is substituted in the 3 position by an amino group, wherein the piperidin-1-yl moiety may additionally be substituted by a methyl group, or a hexahydroazepin-1-yl group which is substituted in the 3 position by an amino group, unless otherwise stated, the abovementioned alkyl and alkenyl groups may be straight-chained or branched.
4. Compound of formula I according to claim 1, 2 or 3, a tautomer, enantiomer, diastereomer, mixture thereof or a salt thereof wherein R1 denotes a hydrogen atom, a C1-4-alkyl group, a C3-5-alkenyl group, a 2-propen-1-yl group which is substituted by a methoxycarbonyl group, a C3-5-alkynyl group, a phenyl-C1-4-alkyl group wherein the phenyl moiety may be substituted by one or two fluorine atoms, one or two chlorine atoms, a bromine atom, one to three methyl groups, a trifluoromethyl, hydroxy, methoxy, nitro, amino, carboxy or ethoxycarbonyl group, a 2-phenylethyl group wherein the ethyl moiety is substituted in the 2 position by a hydroxy, methoxy or hydroxyimino group, a phenylcarbonylmethyl group wherein the phenyl moiety may be substituted by a fluorine atom or by a methyl, aminocarbonyl, aminosulphonyl, cyano, hydroxy, methoxy, phenoxy, benzyloxy, 2-propen-1-yloxy, 2-propyn-1-yloxy, cyanomethoxy, (methoxycarbonyl)methoxy, (aminocarbonyl)methoxy, (methylaminocarbonyl)-methoxy, (dimethylaminocarbonyl)methoxy, methylsulphonyloxy, phenylsulphonyloxy, nitro, amino, (methoxycarbonyl)methylamino, acetylamino, methoxycarbonylamino, methylsulphonylamino, bis-(methylsulphonyl)-amino, aminocarbonylamino, dimethylaminocarbonylamino, (methylamino)thiocarbonylamino, (ethoxycarbonylamino)carbonylamino or cyanomethylamino group, a phenylcarbonylmethyl group wherein the phenyl moiety is substituted by two methoxy groups or by a bromine atom and by a dimethylamino group, a 2-(phenylcarbonyl)ethyl group, a 2-phenylethenyl group, a 2-(phenoxy)ethyl group, a phenylsulphanylmethyl or phenylsulphinylmethyl group, a naphthylmethyl or naphthylethyl group, an isoxazolylmethyl, thiazolylmethyl, pyridylmethyl, benzo[d]isoxazolylmethyl, benzo[d]isothiazolylmethyl, (1H-indazol-3-yl)methyl, quinolinylmethyl or isoquinolinylmethyl group, wherein the heterocyclic moiety may be substituted in each case by a methyl group, an isoquinolinylmethyl group wherein the isoquinolinyl moiety is substituted by a nitro or amino group, a (1,2-dihydro-2-oxo-quinolin-4-yl)methyl group, a pyrrolylethyl, triazolylethyl, thienylethyl, thiazolylethyl or pyridylethyl group, wherein the heterocyclic moiety may be substituted in each case by a methyl group, a thienylcarbonylmethyl group, a methyl group which is substituted by a cyclopropyl, cyano, carboxy, aminocarbonyl or methoxycarbonyl group, an ethyl group which is substituted in the 2 position by a hydroxy, methoxy, dimethylamino, carboxy or methoxycarbonyl group, or a propyl group which is substituted in the 3 position by a hydroxy, dimethylamino, carboxy or methoxycarbonyl group, a 2-oxopropyl group or an amino or benzoylamino group, R2 denotes a hydrogen atom, a C1-6-alkyl group, an ethenyl group, a 2-propen-1-yl or 2-propyn-1-yl group, a phenyl group, a phenyl-C1-4-alkyl group wherein the phenyl moiety may be substituted by a fluorine atom, a methyl or methoxy group, a phenylcarbonylmethyl group, a 2-phenylethenyl group, a methyl group which is substituted by a cyclopropyl, cyano, carboxy or methoxy-carbonyl group, or an ethyl group which is substituted in the 2 position by a cyano, hydroxy, methoxy or dimethylamino group, R3 denotes a C4-6-alkenyl group, a 1-cyclopenten-1-ylmethyl or 1-cyclohexen-1-ylmethyl group, a 2-propyn-1-yl, 2-butyn-1-yl or 2-pentyn-1-yl group, a phenyl group which may be substituted by a fluorine atom or a cyano, methyl or trifluoromethyl group, a phenyl group which is substituted by two methyl groups, a benzyl group wherein the phenyl moiety may be substituted by one or two fluorine atoms, an iodine atom or a cyano, nitro or amino group, a furanylmethyl or thienylmethyl group or a cyclopropyl m ethyl group and R4 denotes a piperidin-1-yl group which is substituted in the 3 position by an amino group, wherein the piperidin-1-yl moiety may additionally be substituted by a methyl group, or a hexahydroazepin-1-yl group which is substituted in the 3 position by an amino group, unless otherwise stated, the abovementioned alkyl and alkenyl groups may be straight-chained or branched.
5. Compound of formula I according to claim 1, a tautomer, enantiomer, diastereomer, mixture thereof or a salt thereof, wherein R1, R2 and R3 are defined as in claim 1 or 2 and R4 denotes a piperidin-1-yl or hexahydroazepin-1-yl group which is substituted in the 3 position by an amino group and may additionally be substituted by one or two C1-3-alkyl groups.
6. A compound of formula a tautomer, enantiomer, diastereomer, mixture thereof or a salt thereof, wherein R1, R3 and R4 are as defined in claim 1, 2, 3, 4 or 5, and R2 is a C1-alkyl group, which may be straight-chained or branched.
7. The compound:
1,3-dimethyl-7-benzyl-8-(3-amino-pyrrolidin-1-yl)-xanthine;
1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-pyrrolidin-1-yl)-xanthine;
1,3-dimethyl-7-benzyl-8-(3-amino-piperidin-1-yl)-xanthine;

1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine;
1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-(4-amino-piperidin-1-yl)-xanthine;
1,3-dimethyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine;

1,3-dimethyl-7-[(1-cyclopenten-1-yl)methyl]-8-(3-amino-piperidin-1-yl)-xanthine;
1,3-dimethyl-7-(2-thienylmethyl)-8-(3-amino-piperidin-1-yl)-xanthine;
1,3-dimethyl-7-(3-fluorobenzyl)-8-(3-amino-piperidin-1-yl)-xanthine;
1,3-dimethyl-7-(2-fluorobenzyl)-8-(3-amino-piperidin-1-yl)-xanthine;
1,3-dimethyl-7-(4-fluorobenzyl)-8-(3-amino-piperidin-1-yl)-xanthine;
1,3-dimethyl-7-(2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine;
1,3-bis-(cyclopropylmethyl)-7-benzyl-8-(3-amino-piperidin-1-yl)-xanthine;
(R)-1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine;
(S)-1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine;
1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-hexahydroazepin-1-yl)-xanthine;

1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-(4-amino-hexahydroazepin-1-yl)-xanthine;

1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-(3-methylamino-piperidin-1-yl)-xanthine;
1-(2-phenylethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine;

1-[2-(thiophen-2-yl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine;

1-[2-(thiophen-3-yl)-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine;

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

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

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

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

1-(2-phenyl-ethyl)-3-methyl -7-(3-methyl-2-buten-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine;

1-(2-phenyl-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-((R)-3-amino-piperidin-yl)-xanthine;

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

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

1-(2-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-methyl -7-(3-methyl-2-buten-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine;

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

1-[(isoquinolin-1-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine; or 1-[(1-naphthyl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-yl)-xanthine;

or a salt thereof.
8. A physiologically acceptable salt of the compound as defined in claim 1, 2, 3, 4, 5, 6 or 7, with an inorganic or organic acid or base.
9. A pharmaceutical composition comprising:

a compound as defined in claim 1, 2, 3, 4, 5 or 6 a tautomer, enantiomer, diastereomer, mixture thereof or a salt thereof;

a compound as defined in claim 7, or a salt thereof; or a physiologically acceptable salt as defined in claim 8; and one or more inert carriers and/or diluents.
10. Use of:

a compound as defined in claim 1, 2, 3, 4, 5 or 6 a tautomer, enantiomer, diastereomer, mixture thereof or a salt thereof;

a compound as defined in claim 7, or a salt thereof; or a physiologically acceptable salt as defined in claim 8;

for preparing a pharmaceutical composition for the treatment of type I or type II
diabetes mellitus, arthritis, obesity, allograft transplantation or osteoporosis caused by calcitonin.
11. Use of:

a compound as defined in claim 1, 2, 3, 4, 5 or 6 a tautomer, enantiomer, diastereomer, mixture thereof or a salt thereof;

a compound as defined in claim 7, or a salt thereof; or a physiologically acceptable salt as defined in claim 8;

for preparing a pharmaceutical composition for the treatment of type II
diabetes mellitus or obesity.
12. Use of:

a compound as defined in claim 1, 2, 3, 4, 5 or 6 a tautomer, enantiomer, diastereomer, mixture thereof or a salt thereof;

a compound as defined in claim 7, or a salt thereof; or a physiologically acceptable salt as defined in claim 8;
for the inhibition of dipeptidylpeptidase-IV (DPP-IV).
13. Use of:

a compound as defined in claim 1, 2, 3, 4, 5 or 6 a tautomer, enantiomer, diastereomer, mixture thereof or a salt thereof;

a compound as defined in claim 7, or a salt thereof; or a physiologically acceptable salt as defined in claim 8 for the treatment of type I or type II diabetes mellitus, arthritis, obesity, allograft transplantation or osteoporosis caused by calcitonin.
14. Use of:

a compound as defined in claim 1, 2, 3, 4, 5 or 6 a tautomer, enantiomer, diastereomer, mixture thereof or a salt thereof;

a compound as defined in claim 7, or a salt thereof; or a physiologically acceptable salt as defined in claim 8 for the treatment of type II diabetes mellitus.
15. Use of:

a compound as defined in claim 1, 2, 3, 4, 5 or 6 a tautomer, enantiomer, diastereomer, mixture thereof or a salt thereof;

a compound as defined in claim 7, or a salt thereof; or a physiologically acceptable salt as defined in claim 8 for the treatment of obesity.
16. Use according to claim 12, 13, 14 or 15 in combination with metformin, a sulphonylurea, nateglinide, repaglinide, a thiazolidinedione, a PPAR-gamma-agonist, an alpha-glucosidase inhibitor, insulin or an insulin analogue, or GLP-1 or a GLP-1 analogue.
17. Use according to claim 12, 13, 14 or 15 in combination with metformin, a sulphonylurea or a thiazolidinedione.
18. Use according to claim 17, wherein the thiazolidinedione is pioglitazone.
19. The pharmaceutical composition according to claim 9 for the treatment of type I or type II diabetes mellitus, arthritis, obesity, allograft transplantation or osteoporosis caused by calcitonin.
20. The pharmaceutical composition according to claim 9 for the treatment of type II diabetes mellitus.
21. The pharmaceutical composition according to claim 9 for the treatment of obesity.
22. The pharmaceutical composition according to claim 9, 19, 20 or 21, which is an oral dosage form.
23. The pharmaceutical composition according to claim 22, wherein the oral dosage form is a tablet.
24. Process for preparing a pharmaceutical composition as defined in claim 9, comprising incorporating:

a compound as defined in claim 1, 2, 3, 4, 5 or 6 a tautomer, enantiomer, diastereomer, mixture thereof or a salt thereof;

a compound as defined in claim 7, or a salt thereof; or a physiologically acceptable salt as defined in claim 8 in one or more inert carriers and/or diluents by a non-chemical method.
25. Process for preparing a compound of formula a tautomer, enantiomer, diastereomer, mixture thereof or a salt thereof, the process comprising:

a) for a compound of formula I wherein R4 is one of the groups defined below linked to the xanthine skeleton via a nitrogen atom:

reacting a compound of formula wherein R1 to R3 are defined as defined below, and Z1 denotes a leaving group with a compound of formula H-R4' (IV), wherein R4'denotes one of the groups defined for R4 below, which is linked to the xanthine skeleton of formula I via a nitrogen atom, or b) for compound of formula I wherein R4 as defined below contains an amino group or an alkylamino group optionally substituted in the alkyl moiety:
deprotecting a compound of formula wherein R1, R2 and R3 are as defined as below and R4" contains an N-tert.-butyloxycarbonylamino group or an N-tert.-butyloxycarbonyl-N-alkylamino group optionally substituted in the alkyl moiety, or c) for a compound of formula I wherein R2 denotes a hydrogen atom:
deprotecting a compound of formula wherein R1, R3 and R4 are defined below and R2' denotes a protecting group;
while a compound of formula I thus obtained which contains an amino, alkylamino or imino group may be converted by acylation or sulphonylation into a corresponding acyl or sulphonyl compound of formula I;

a compound of formula I thus obtained which contains an amino, alkylamino or imino group may be converted by alkylation or reductive alkylation into a corresponding alkyl compound of formula I;

a compound of formula I thus obtained which contains a nitro group may be converted by reduction into a corresponding amino compound;

a compound of formula I thus obtained which contains an imino group may be converted by nitrosation and subsequent reduction into a corresponding N-amino-imino compound;

a compound of formula I thus obtained which contains a C1-3-alkyloxycarbonyl group may be converted by cleavage of the ester into the corresponding carboxy compound;

a compound of formula I thus obtained wherein R1 contains a carbonyl group may be converted by reaction with hydroxylamine into a corresponding oxime of formula I;

a compound of formula I thus obtained which contains a carboxy group may be converted by esterification into a corresponding ester of formula I; or a compound of formula I thus obtained which contains a carboxy or ester group may be converted by reaction with an amine into a corresponding amide of formula I, wherein R1 denotes a hydrogen atom, a C1-6-alkyl group, a C3-6-alkenyl group, a C3-4-alkenyl group which is substituted by a C1-2-alkyloxy-carbonyl group, a C3-6-alkynyl group, a C3-6-cycloalkyl-C1-3-alkyl group, a phenyl group which may be substituted by a fluorine, chlorine or bromine atom or by a methyl, trifluoromethyl, hydroxy or methoxy group, a phenyl-C1-4-alkyl group wherein the phenyl moiety is substituted by R10 to R12, wherein R10 denotes a hydrogen atom, a fluorine, chlorine or bromine atom, a CI-4-alkyl, trifluoromethyl, hydroxymethyl, C3-6-cycloalkyl, ethynyl or phenyl group, a hydroxy, C1-4-alkyloxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, phenoxy, benzyloxy, 2-propen-1-yloxy, 2-propyn-1-yloxy, cyano-C1-2-alkyloxy, C1-2-alkylsulphonyloxy, phenylsulphonyloxy, carboxy-C1-3-alkyloxy, C1-3-alkyloxy-carbonyl-C1-3-alkyloxy, aminocarbonyl-C1-3-alkyloxy, C1-2-alkyl-aminocarbonyl-C1-3-alkyloxy, di-(C1-2-alkyl)aminocarbonyl-C1-3-alkyloxy, pyrrolidin-1-yl-carbonyl-C1-3-alkyloxy, piperidin-1-ylcarbonyl-C1-3-alkyloxy, morpholin-4-ylcarbonyl-C1-3-alkyloxy, methylsulphanylmethoxy, methylsulphinylmethoxy, methylsulphonylmethoxy, C3-6-cycloalkyloxy or C3-6-cycloalkyl-C1-2-alkyloxy group, a carboxy, C1-3-alkyloxycarbonyl, carboxy-C1-3-alkyl, C1-3-alkyloxy-carbonyl-C1-3-alkyl, aminocarbonyl, C1-2-alkylaminocarbonyl, di-(C1-2-alkyl)aminocarbonyl, morpholin-4-ylcarbonyl or cyano group, a nitro, amino, C1-2-alkylamino, di-(C1-2-alkyl)amino, cyano-C1-2-alkylamino, [N-(cyano-C1-2-alkyl)-N-C1-2-alkyl-amino], C1-2-alkyloxy-carbonyl-C1-2-alkylamino, C1-2-alkyl-carbonylamino, C1-2-alkyloxy-carbonylamino, C1-3-alkylsulphonylamino, bis-(C1-2-alkylsulphonyl)-amino, aminosulphonylamino, C1-2-alkylamino-sulphonylamino, di-(C1-2-alkyl)amino-sulphonylamino, morpholin-4-yl-sulphonylamino, (C1-2-alkylamino)thiocarbonylamino, (C1-2-alkyloxy-carbonylamino)carbonylamino, aminocarbonylamino, C1-2-alkylaminocarbonylamino, di-(C1-2-alkyl)aminocarbonylamino or morpholin-4-ylcarbonylamino group, a 2-oxo-imidazolidin-1-yl, 3-methyl-2-oxo-imidazolidin-1-yl, 2,4-dioxo-imidazolidin-1-yl, 3-methyl-2,4-dioxo-imidazolidin-1-yl, 2,5-dioxo-imidazolidin-1-yl, 3-methyl-2,5-dioxo-imidazolidin-1-yl, 2-oxo-hexahydropyrimidin-1-yl or 3-methyl-2-oxo-hexahydropyrimidin-1-yl group, or a C1-2-alkylsulphanyl, C1-2-alkylsulphinyl, C1-2-alkylsulphonyl, aminosulphonyl, C1-2-alkylaminosulphonyl or di-(C1-2-alkyl)aminosulphonyl group, and R11 and R12, which may be identical or different, denote a hydrogen, fluorine, chlorine or bromine atom or a methyl, cyano, trifluoromethyl or methoxy group, or, R11 together with R12, if they are bound to adjacent carbon atoms, also denote a methylenedioxy, difluoromethylenedioxy, 1,3-propylene or 1,4-butylene group, a phenyl-C1-3-alkyl group wherein the alkyl moiety is substituted by a carboxy, C1-2-alkyloxy-carbonyl, aminocarbonyl, C1-2-alkylaminocarbonyl or di-(C1-2-alkyl)aminocarbonyl group, a phenyl-C2-3-alkenyl group, wherein the phenyl moiety may be substituted by a fluorine, chlorine or bromine atom or by a methyl, trifluoromethyl or methoxy group, a phenyl-(CH2)m-A-(CH2)n group wherein the phenyl moiety is substituted by R10 to R12, wherein R10 to R12 are as hereinbefore defined and A denotes a carbonyl, hydroxyiminomethylene or C1-2-alkyloxyiminomethylene group, m denotes the number 0 or 1 and n denotes the number 1 or 2, a phenylcarbonylmethyl group wherein the phenyl moiety is substituted by R10 to R12, wherein R10 to R12 are as hereinbefore defined and the methyl moiety is substituted by a methyl or ethyl group, a phenylcarbonylmethyl group wherein two adjacent hydrogen atoms of the phenyl moiety are replaced by a -O-CO-NH, -NH-CO-NH, -N=CH-NH, -N=CH-O or -O-CH2-CO-NH- bridge, wherein the abovementioned bridges may be substituted by one or two methyl groups, a phenyl-(CH2)m-B-(CH2)n group wherein the phenyl moiety is substituted by R10 to R12, wherein R10 to R12, m and n are as hereinbefore defined and B denotes a methylene group which is substituted by a hydroxy or C1-2-alkyloxy group and is optionally additionally substituted by a methyl group, a naphthylmethyl or naphthylethyl group, wherein the naphthyl moiety is substituted in each case by R10 to R12, wherein R10 to R12 are as hereinbefore defined, a [1,4]naphthoquinon-2-yl, chromen-4-on-3-yl or 1-oxoindan-2-yl group, a heteroaryl-C1-3-alkyl group, wherein by the term heteroaryl is meant a pyrrolyl, furanyl, thienyl, pyridyl, indolyl, benzofuranyl, benzothiophenyl, quinolinyl or isoquinolinyl group, or a pyrrolyl, furanyl, thienyl or pyridyl group wherein one or two methyne groups are replaced by nitrogen atoms, or an indolyl, benzofuranyl, benzothiophenyl, quinolinyl or isoquinolinyl group wherein one to three methyne groups are replaced by nitrogen atoms, or a 1,2-dihydro-2-oxo-pyridinyl, 1,4-dihydro-4-oxo-pyridinyl, 2,3-dihydro-3-oxo-pyridazinyl, 1,2,3,6-tetrahydro-3,6-dioxo-pyridazinyl, 1,2-dihydro-2-oxo-pyrimidinyl, 3,4-dihydro-4-oxo-pyrimidinyl, 1,2,3,4-tetrahydro-2,4-dioxo-pyrimidinyl, 1,2-dihydro-2-oxo-pyrazinyl, 1,2,3,4-tetrahydro-2,3-dioxo-pyrazinyl, 2,3-dihydro-2-oxo-indolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydro-2-oxo-1H-benzimidazolyl, 2,3-dihydro-2-oxo-benzoxazolyl, 1,2-dihydro-2-oxo-quinolinyl, 1,4-dihydro-4-oxo-quinolinyl, 1,2-dihydro-1-oxo-isoquinolinyl, 1,4-dihydro-4-oxo-cinnolinyl, 1,2-dihydro-2-oxo-quinazolinyl, 1,4-dihydro-4-oxo-quinazolinyl, 1,2,3,4-tetrahydro-2,4-dioxo-quinazolinyl, 1,2-dihydro-2-oxoquinoxalinyl, 1,2,3,4-tetrahydro-2,3-dioxo-quinoxalinyl, 1,2-dihydro-1-oxo-phthalazinyl, 1,2,3,4-tetrahydro-1,4-dioxo-phthalazinyl, chromanyl, cumarinyl, 2,3-dihydro-benzo[1,4]dioxinyl or 3,4-dihydro-3-oxo-2H-benzo[1,4]oxazinyl group, wherein the abovementioned heteroaryl groups may be substituted by R10 to R12, wherein R10 to R12 are as hereinbefore defined, a furanyl-A-CH2, thienyl-A-CH2, thiazolyl-A-CH2 or pyridyl-A-CH2 group, wherein A
is as hereinbefore defined, a furanyl-B-CH2, thienyl-B-CH2, thiazolyl-B-CH2 or pyridyl-B-CH2 group, wherein B
is as hereinbefore defined, a C1-4-alkyl-A-(CH2)n group, wherein A and n are as hereinbefore defined, a C3-6-cycloalkyl-(CH2)m-A-(CH2)n group, wherein A, m and n are as hereinbefore defined, a C3-6-cycloalkyl-(CH2)m-B-(CH2)n group, wherein B, m and n are as hereinbefore defined, a R21-A-(CH2)n group wherein R21 denotes a C1-2-alkyloxycarbonyl, aminocarbonyl, C1-2-alkylaminocarbonyl, di-(C1-2-alkyl)aminocarbonyl, pyrrolidin-1-yl-carbonyl, piperidin-1-yl-carbonyl or morpholin-4-yl-carbonyl group and A
and n are as hereinbefore defined, a phenyl-D-C1-3-alkyl group wherein the phenyl moiety is optionally substituted by a fluorine, chlorine or bromine atom, a methyl, trifluoromethyl or methoxy group and D denotes an oxygen or sulphur atom, a sulphinyl or sulphonyl group, a C1-4-alkyl group substituted by a group R a, wherein R a denotes a cyano, carboxy, C1-3-alkyloxy-carbonyl, aminocarbonyl, C1-2-alkyl-aminocarbonyl, di-(C1-2-alkyl)aminocarbonyl, pyrrolidin-1-yl-carbonyl, piperidin-1-ylcarbonyl or morpholin-4-ylcarbonyl group, a C2-4-alkyl group substituted by a group R b, wherein R b denotes a hydroxy, C1-3-alkyloxy, amino, C1-3-alkylamino, di-(C1-3-alkyl)-amino, pyrrolidin-1-yl, piperidin-1-yl, morpholin-4-yl, piperazin-1-yl, 4-methyl-piperazin-1-yl or 4-ethyl-piperazin-1-yl group and is isolated from the cyclic nitrogen atom in the 1 position of the xanthine skeleton by at least two carbon atoms, or an amino or benzoylamino group, R2 denotes a hydrogen atom, a C1-6-alkyl group, a C2-4-alkenyl group, a C3-4-alkynyl group, a C3-6-cycloalkyl group, a C3-6-cycloalkyl-C1-3-alkyl group, a tetrahydrofuran-3-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, tetrahydrofuranylmethyl or tetrahydropyranylmethyl group, a phenyl group which is optionally substituted by a fluorine, chlorine or bromine atom or by a methyl, trifluoromethyl, hydroxy, methoxy, difluoromethoxy or trifluoromethoxy group, a phenyl-C1-4-alkyl group wherein the phenyl moiety is optionally substituted by a fluorine, chlorine or bromine atom, a methyl, trifluoromethyl, dimethylamino, hydroxy, methoxy, difluoromethoxy or trifluoromethoxy group, a phenyl-C2-3-alkenyl group, wherein the phenyl moiety may be substituted by a fluorine, chlorine or bromine atom or by a methyl, trifluoromethyl or methoxy group, a phenylcarbonyl-C1-2-alkyl group wherein the phenyl moiety is optionally substituted by a fluorine, chlorine or bromine atom, a methyl, trifluoromethyl, hydroxy, methoxy, difluoromethoxy or trifluoromethoxy group, a heteroaryl-C1-3-alkyl group, wherein the term heteroaryl is as hereinbefore defined, a furanylcarbonylmethyl, thienylcarbonylmethyl, thiazolylcarbonylmethyl or pyridylcarbonylmethyl group, a C1-4-alkyl-carbonyl-C1-2-alkyl group, a C3-6-cycloalkyl-carbonyl-C1-2-alkyl group, a phenyl-D-C1-3-alkyl group wherein the phenyl moiety is optionally substituted by a fluorine, chlorine or bromine atom, a methyl, trifluoromethyl, hydroxy, methoxy, difluoromethoxy or trifluoromethoxy group, and D is as hereinbefore defined, or a C1-4-alkyl group substituted by a group R a, wherein R a is as hereinbefore defined, or a C2-4-alkyl group substituted by a group R b, wherein R b is as hereinbefore defined and is isolated from the cyclic nitrogen atom in the 3 position of the xanthine skeleton by at least two carbon atoms, R3 denotes a C1-3-alkyl group substituted by the group R c, wherein R c denotes a C3-7-cycloalkyl group optionally substituted by one or two C1-3-alkyl groups, a C5-7-cycloalkenyl group optionally substituted by one or two C1-3-alkyl groups or an aryl group or a furanyl, thienyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyridyl, pyridazinyl, pyrimidyl or pyrazinyl group, wherein the abovementioned heterocyclic groups may each be substituted by one or two C1-3-alkyl groups or by a fluorine, chlorine, bromine or iodine atom or by a trifluoromethyl, cyano or C1-3-alkyloxy group, a C3-8-alkenyl group, a C3-6-alkenyl group substituted by a fluorine, chlorine or bromine atom, or a trifluoromethyl group, a C3-8-alkynyl group, an aryl group or an aryl-C2-4-alkenyl group, and R4 denotes an azetidin-1-yl or pyrrolidin-1-yl group which is substituted in the 3 position by an R e NR d group and may additionally be substituted by one or two C1-3-alkyl groups, wherein R e denotes a hydrogen atom or a C1-3-alkyl group and R d denotes a hydrogen atom or a C1-3-alkyl group, a piperidin-1-yl or hexahydroazepin-1-yl group which is substituted in the 3 position or in the 4 position by an R e NR d group and may additionally be substituted by one or two C1-3-alkyl groups, wherein R e and R d are as hereinbefore defined, a 3-amino-piperidin-1-yl group wherein the piperidin-1-yl moiety is additionally substituted by an aminocarbonyl, C1-2-alkyl-aminocarbonyl, di-(C1-2-alkyl)aminocarbonyl, pyrrolidin-1-yl-carbonyl, (2-cyano-pyrrolidin-1-yl-)carbonyl, thiazolidin-3-yl-carbonyl, (4-cyano-thiazolidin-3-yl)carbonyl, piperidin-1-ylcarbonyl or morpholin-4-ylcarbonyl group, a 3-amino-piperidin-1-yl group wherein the piperidin-1-yl moiety is additionally substituted in the 4 position or in the 5 position by a hydroxy or methoxy group, a 3-amino-piperidin-1-yl group wherein the methylene group is replaced in the position or in the 6 position by a carbonyl group, a piperidin-1-yl or hexahydroazepin-1-yl group substituted in the 3 position by an amino, C1-3-alkylamino or di-(C1-3-alkyl)-amino group, wherein in each case two hydrogen atoms on the carbon skeleton of the piperidin-1-yl or hexahydroazepin-1-yl group are replaced by a straight-chain alkylene bridge, this bridge containing 2 to 5 carbon atoms if the two hydrogen atoms are located on the same carbon atom, or 1 to 4 carbon atoms if the hydrogen atoms are located on adjacent carbon atoms, or 1 to 4 carbon atoms if the hydrogen atoms are located on carbon atoms which are separated by one atom, or 1 to 3 carbon atoms if the two hydrogen atoms are located on carbon atoms separated by two atoms, an azetidin-1-yl, pyrrolidin-1-yl, piperidin-1-yl or hexahydroazepin-1-yl group which is substituted by an amino-C1-3-alkyl, C1-3-alkylamino-C1-3-alkyl or a di-(C1-alkyl)amino-C1-3-alkyl group, a 3-imino-piperazin-1-yl, 3-imino-[1,4]diazepan-1-yl or 5-imino-[1,4]diazepan-1-yl group optionally substituted by one or two C1-3-alkyl groups on the carbon skeleton, a [1,4]diazepan-1 -yl group optionally substituted by one or two C1-3-alkyl groups, which is substituted in the 6 position by an amino group, a C3-7-cycloalkyl group which is substituted by an amino, C1-3-alkylamino or di-(C1-3-alkyl)-amino group, a C3-7-cycloalkyl group which is substituted by an amino-C1-3-alkyl, C1-3-alkylamino-C1-3-alkyl or a di-(C1-3-alkyl)amino-C1-3-alkyl group, a C3-7-cycloalkyl-C1-2-alkyl group wherein the cycloalkyl moiety is substituted by an amino, C1-3-alkylamino or di-(C1-3-alkyl)-amino group, a C3-7-cycloalkyl-C1-2-alkyl group wherein the cycloalkyl moiety is substituted by an amino-C1-3-alkyl, C1-3-alkylamino-C1-3-alkyl or a di-(C1-3-alkyl)amino-C1-3-alkyl group, a C3-7-cycloalkylamino group wherein the cycloalkyl moiety is substituted by an amino, C1-3-alkylamino or di-(C1-3-alkyl)-amino group, wherein the two nitrogen atoms are separated from one another at the cycloalkyl moiety by at least two carbon atoms, a N-(C3-7-cycloalkyl)-N-(C1-3-alkyl)-amino group wherein the cycloalkyl moiety is substituted by an amino, C1-3-alkylamino or di-(C1-3-alkyl)-amino group, wherein the two nitrogen atoms are separated from one another at the cycloalkyl moiety by at least two carbon atoms, a C3-7-cycloalkylamino group wherein the cycloalkyl moiety is substituted by an amino-C1-3-alkyl, C1-3-alkylamino-C1-3-alkyl or a di-(C1-3-alkyl)amino-C1-3-alkyl group, a N-(C3-7-cycloalkyl)-N-(C1-3-alkyl)-amino group wherein the cycloalkyl moiety is substituted by an amino-C1-3-alkyl, C1-3-alkylamino-C1-3-alkyl or a di-(C1-3-alkyl)amino-C1-3-alkyl group, a C3-7-cycloalkyl-Cl-Z-alkyl-amino group wherein the cycloalkyl moiety is substituted by an amino, C1-3-alkylamino or di-(C1-3-alkyl)-amino group, a N-(C3-7-cycloalkyl-C1-2-alkyl)-N-(C1-2-alkyl)-amino group wherein the cycloalkyl moiety is substituted by an amino, C1-3-alkylamino or di-(C1-3-alkyl)-amino group, a C3-7-cycloalkyl-C1-2-alkyl-amino group wherein the cycloalkyl moiety is substituted by an amino-C1-3-alkyl, C1-3-alkylamino-C1-3-alkyl or a di-(C1-3-alkyl)amino-C1-3-alkyl group, an N-(C3-7-cycloalkyl-C1-2-alkyl)-N-(C1-2-alkyl)-amino group wherein the cycloalkyl moiety is substituted by an amino-C1-3-alkyl, C1-3-alkylamino-C1-3-alkyl or a di-(C1-3-alkyl)amino-C1-3-alkyl group, an amino group substituted by the groups R15 and R16 wherein R15 denotes a C1-3-alkyl group and R16 denotes a R"-C2-3-alkyl group, wherein the C2-3-alkyl moiety is straight-chained and may be substituted by one to four C1-3-alkyl groups, which may be identical or different, or by an aminocarbonyl, C1-2-alkyl-aminocarbonyl, di-(C1-2-alkyl)aminocarbonyl, pyrrolidin-1-yl-carbonyl, (2-cyano-pyrrolidin-1-yl)carbonyl, thiazolidin-3-yl-carbonyl, (4-cyano-thiazolidin-3-yl)carbonyl, piperidin-1-ylcarbonyl or morpholin-4-ylcarbonyl group and R17 denotes an amino, C1-3-alkylamino or di-(C1-3-alkyl)-amino group, an amino group substituted by the group R20, wherein R20 denotes an azetidin-3-yl, azetidin-2-ylmethyl, azetidin-3-ylmethyl, pyrrolidin-3-yl, pyrrolidin-2-ylmethyl, pyrrolidin-3-ylmethyl, piperidin-3-yl, piperidin-4-yl, piperidin-2-ylmethyl, piperidin-3-ylmethyl or piperidin-4-ylmethyl group, wherein the groups mentioned for R20 may each be substituted by one or two C1-3-alkyl groups, an amino group substituted by the groups R15 and R20, wherein R15 and R20 are as hereinbefore defined, wherein the groups mentioned for R20 may each be substituted by one or two C1-3-alkyl groups, a R19-C3-4-alkyl group wherein the C3-4-alkyl moiety is straight-chained and may be substituted by the group R15 and may additionally be substituted by one or two C1-3-alkyl groups, wherein R15 is as hereinbefore defined and R19 denotes an amino, C1-3-alkylamino or di-(C1-3-alkyl)-amino group, a 3-amino-2-oxo-piperidin-5-yl or 3-amino-2-oxo-1-methyl-piperidin-5-yl group, a pyrrolidin-3-yl, piperidin-3-yl, piperidin-4-yl, hexahydroazepin-3-yl or hexahydroazepin-4-yl group, which is substituted in the 1 position by an amino, C1-3-alkylamino or di-(C1-3-alkyl)amino group, or an azetidin-2-yl-C1-2-alkyl, azetidin-3-yl-C1-2-alkyl, pyrrolidin-2-yl-C1-2-alkyl, pyrrolidin-3-yl, pyrrolidin-3-yl-C1-2-alkyl, piperidin-2-yl-C1-2-alkyl, piperidin-3-yl, piperidin-3-yl-C1-2-alkyl, piperidin-4-yl or piperidin-4-yl-C1-2-alkyl group, wherein the abovementioned groups may each be substituted by one or two C1-3-alkyl groups, while by the aryl groups mentioned in the definition of the groups mentioned above are meant phenyl or naphthyl groups which may be mono- or disubstituted independently of one another by R h, while the substituents may be identical or different and R h denotes a fluorine, chlorine, bromine or iodine atom, a trifluoromethyl, cyano, nitro, amino, C1-3-alkyl, cyclopropyl, ethenyl, ethynyl, hydroxy, C1-3-alkyloxy, difluoromethoxy or trifluoromethoxy group and unless otherwise stated, the abovementioned alkyl and alkenyl groups may be straight-chained or branched, with the proviso that the compounds 1,3-diethyl-7-(4-methoxybenzyl)-8-[(piperidin-4-yl)amino]-xanthine, and 1,3-diethyl-7-(4-hydroxybenzyl)-8-[(piperidin-4-yl)amino]-xanthine are excluded.
26. Process according to claim 25, wherein Z1 is a halogen atom, a substituted hydroxy, mercapto, sulphinyl, sulphonyl or sulphonyloxy group, or a methanesulphonyl or methanesulphonyloxy group, and R2' is a methoxymethyl, benzyloxymethyl, methoxyethoxymethyl or 2-(trimethylsilyl)ethyloxymethyl group.
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DE2001109021 DE10109021A1 (en) 2001-02-24 2001-02-24 New 8-substituted-xanthine derivatives, useful e.g. for treating diabetes and arthritis, act by inhibiting dipeptidylpeptidase-IV
DE2001117803 DE10117803A1 (en) 2001-04-10 2001-04-10 New 8-substituted-xanthine derivatives, useful e.g. for treating diabetes and arthritis, act by inhibiting dipeptidylpeptidase-IV
DE10117803.4 2001-04-10
DE10140345.3 2001-08-17
DE10140345A DE10140345A1 (en) 2001-08-17 2001-08-17 New 8-substituted-xanthine derivatives, useful e.g. for treating diabetes and arthritis, act by inhibiting dipeptidylpeptidase-IV
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DE2002103486 DE10203486A1 (en) 2002-01-30 2002-01-30 New 8-substituted-xanthine derivatives, useful e.g. for treating diabetes and arthritis, act by inhibiting dipeptidylpeptidase-IV
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Families Citing this family (193)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB0014861D0 (en) * 2000-06-16 2000-08-09 Pharmacia & Upjohn Spa Novel telomerase inhibitors
EP1301187B1 (en) * 2000-07-04 2005-07-06 Novo Nordisk A/S Purine-2,6-diones which are inhibitors of the enzyme dipeptidyl peptidase iv (dpp-iv)
US6821978B2 (en) * 2000-09-19 2004-11-23 Schering Corporation Xanthine phosphodiesterase V inhibitors
HU230382B1 (en) * 2001-02-24 2016-03-29 Boehringer Ingelheim Pharma Gmbh & Co. Kg Xanthine derivative, production and use thereof as a medicament
US6869947B2 (en) 2001-07-03 2005-03-22 Novo Nordisk A/S Heterocyclic compounds that are inhibitors of the enzyme DPP-IV
KR20040033048A (en) * 2001-09-14 2004-04-17 미츠비시 웰파마 가부시키가이샤 Thiazolidine derivative and medicinal use thereof
AU2002331311A1 (en) * 2001-09-19 2003-04-01 Novo Nordisk A/S Heterocyclic compounds that are inhibitors of the enzyme dpp-iv
AU2002360453C1 (en) * 2001-11-26 2009-06-18 The Brigham And Women's Hospital, Inc. Methods for treating autoimmune disorders, and reagents related thereto
DE60304911D1 (en) * 2002-02-25 2006-06-08 Eisai Co Ltd Xanthine derivatives as DPP-IV inhibitors
CN100497336C (en) * 2002-05-31 2009-06-10 先灵公司 Process for preparing xanthine phosphodiesterase V inhibitors and precursors thereof
CN100348599C (en) 2002-06-06 2007-11-14 卫材R&D管理有限公司 Novel fused imidazole derivative
EP1521584A1 (en) 2002-06-17 2005-04-13 Glaxo Group Limited Purine derivatives as liver x receptor agonists
CA2496249C (en) * 2002-08-21 2012-01-24 Boehringer Ingelheim Pharma Gmbh & Co. Kg 8-[3-amino-piperidin-1-yl]-xanthines, the production thereof and the use of the same as medicaments
AU2013202252B2 (en) * 2002-08-21 2016-05-12 Boehringer Ingelheim Pharma Gmbh & Co. Kg 8-[3-amino-piperidin-1-yl]-xanthines, the production thereof and the use of the same as medicaments
US7407955B2 (en) 2002-08-21 2008-08-05 Boehringer Ingelheim Pharma Gmbh & Co., Kg 8-[3-amino-piperidin-1-yl]-xanthines, the preparation thereof and their use as pharmaceutical compositions
DE10238470A1 (en) * 2002-08-22 2004-03-04 Boehringer Ingelheim Pharma Gmbh & Co. Kg New xanthine derivatives, their production and their use as medicines
US7569574B2 (en) 2002-08-22 2009-08-04 Boehringer Ingelheim Pharma Gmbh & Co. Kg Purine derivatives, the preparation thereof and their use as pharmaceutical compositions
US7495005B2 (en) * 2002-08-22 2009-02-24 Boehringer Ingelheim Pharma Gmbh & Co. Kg Xanthine derivatives, their preparation and their use in pharmaceutical compositions
MXPA05003252A (en) * 2002-09-26 2005-07-05 Eisai Co Ltd Combination drug.
WO2004048379A1 (en) * 2002-11-01 2004-06-10 Sumitomo Pharmaceuticals Co., Ltd. Xanthine compound
DE10251927A1 (en) * 2002-11-08 2004-05-19 Boehringer Ingelheim Pharma Gmbh & Co. Kg New 1,7,8-trisubstituted xanthine derivatives, are dipeptidylpeptidase-IV inhibitors useful e.g. for treating diabetes mellitus type I or II, arthritis or obesity
US7482337B2 (en) 2002-11-08 2009-01-27 Boehringer Ingelheim Pharma Gmbh & Co. Kg Xanthine derivatives, the preparation thereof and their use as pharmaceutical compositions
DE10254304A1 (en) * 2002-11-21 2004-06-03 Boehringer Ingelheim Pharma Gmbh & Co. Kg New xanthine derivatives, their production and their use as medicines
UY28103A1 (en) * 2002-12-03 2004-06-30 Boehringer Ingelheim Pharma NEW IMIDAZO-PIRIDINONAS REPLACED, ITS PREPARATION AND ITS EMPLOYMENT AS MEDICATIONS
US7109192B2 (en) 2002-12-03 2006-09-19 Boehringer Ingelheim Pharma Gmbh & Co Kg Substituted imidazo-pyridinones and imidazo-pyridazinones, the preparation thereof and their use as pharmaceutical compositions
EP1608317B1 (en) * 2003-03-25 2012-09-26 Takeda Pharmaceutical Company Limited Dipeptidyl peptidase inhibitors
AU2004237408C9 (en) 2003-05-05 2010-04-15 Probiodrug Ag Medical use of inhibitors of glutaminyl and glutamate cyclases
PT1620082E (en) 2003-05-05 2010-06-11 Probiodrug Ag Medical use of inhibitors of glutaminyl and glutamate cyclases for treating alzheimer`s disease and down syndrome
US7566707B2 (en) 2003-06-18 2009-07-28 Boehringer Ingelheim International Gmbh Imidazopyridazinone and imidazopyridone derivatives, the preparation thereof and their use as pharmaceutical compositions
US7678909B1 (en) 2003-08-13 2010-03-16 Takeda Pharmaceutical Company Limited Dipeptidyl peptidase inhibitors
US7579357B2 (en) * 2003-08-13 2009-08-25 Takeda Pharmaceutical Company Limited Dipeptidyl peptidase inhibitors
US7169926B1 (en) 2003-08-13 2007-01-30 Takeda Pharmaceutical Company Limited Dipeptidyl peptidase inhibitors
JPWO2005021550A1 (en) * 2003-08-29 2006-10-26 大日本住友製薬株式会社 Bicyclic pyrazole derivatives
JP2007505121A (en) * 2003-09-08 2007-03-08 武田薬品工業株式会社 Dipeptidyl peptidase inhibitor
WO2005030751A2 (en) * 2003-09-08 2005-04-07 Takeda Pharmaceutical Company Limited Dipeptidyl peptidase inhibitors
DE10348044A1 (en) * 2003-10-15 2005-05-19 Imtm Gmbh Dual alanyl aminopeptidase and dipeptidyl peptidase IV inhibitors for the functional influence of different cells and for the treatment of immunological, inflammatory, neuronal and other diseases
DE10348023A1 (en) * 2003-10-15 2005-05-19 Imtm Gmbh New alanyl aminopeptidase inhibitors for the functional manipulation of different cells and for the treatment of immunological, inflammatory, neuronal and other diseases
DE10348022A1 (en) * 2003-10-15 2005-05-25 Imtm Gmbh New dipeptidyl peptidase IV inhibitors for the functional influence of different cells and for the treatment of immunological, inflammatory, neuronal and other diseases
DK1675578T3 (en) 2003-10-15 2013-08-26 Probiodrug Ag Inhibitors of glutaminyl and glutamate cyclases for the treatment of the neurodegenerative diseases FBD and FDD
NZ546887A (en) 2003-11-03 2009-04-30 Probiodrug Ag Combinations useful for the treatment of neuronal disorders
MXPA06005518A (en) 2003-11-17 2006-08-17 Novartis Ag Use of dipeptidyl peptidase iv inhibitors.
DE10355304A1 (en) * 2003-11-27 2005-06-23 Boehringer Ingelheim Pharma Gmbh & Co. Kg Novel 8- (piperazin-1-yl) and 8 - ([1,4] diazepan-1-yl) xanthines, their preparation and their use as pharmaceuticals
WO2005053695A1 (en) * 2003-12-04 2005-06-16 Eisai Co., Ltd. Preventive or therapeutic agent for multiple sclerosis
DE10359098A1 (en) * 2003-12-17 2005-07-28 Boehringer Ingelheim Pharma Gmbh & Co. Kg Novel 2- (piperazin-1-yl) and 2 - ([1,4] diazepan-1-yl) imidazo [4,5-d] pyridazin-4-ones, their preparation and their use as pharmaceuticals
DE10360835A1 (en) * 2003-12-23 2005-07-21 Boehringer Ingelheim Pharma Gmbh & Co. Kg New bicyclic imidazole derivatives are dipeptidylpeptidase-IV inhibitors useful to treat e.g. arthritis, obesity, allograft transplantation and calcitonin-induced osteoporosis
ES2684325T5 (en) 2004-01-20 2024-06-10 Novartis Ag Formulation and direct compression process
JP4996926B2 (en) 2004-02-05 2012-08-08 プロビオドルグ エージー Novel inhibitors of glutaminyl cyclase
EP1781657B1 (en) * 2004-02-14 2013-03-27 GlaxoSmithKline Intellectual Property Development Limited Medicaments with hm74a receptor activity
DE102004008112A1 (en) * 2004-02-18 2005-09-01 Boehringer Ingelheim Pharma Gmbh & Co. Kg New 8-aminopiperidinyl-xanthine derivatives, useful for treating e.g. diabetes, arthritis and osteoporosis, are inhibitors of dipeptidylpeptidase-IV
AU2012202850B2 (en) * 2004-02-18 2015-08-20 Boehringer Ingelheim International Gmbh 8-[3-amino-piperidin-1-yl]-xanthine, the production thereof and the use in the form of a DPP inhibitor
US7501426B2 (en) * 2004-02-18 2009-03-10 Boehringer Ingelheim International Gmbh 8-[3-amino-piperidin-1-yl]-xanthines, their preparation and their use as pharmaceutical compositions
DE502005007196D1 (en) * 2004-02-18 2009-06-10 Boehringer Ingelheim Pharma 8-Ä3-AMINO-PIPERIDIN-1-YLÜ-XANTHINE, THEIR PREPARATION AND THEIR USE AS DPP-IV HEMMER
DE102004009039A1 (en) * 2004-02-23 2005-09-08 Boehringer Ingelheim Pharma Gmbh & Co. Kg 8- [3-Amino-piperidin-1-yl] xanthines, their preparation and use as pharmaceuticals
US7732446B1 (en) 2004-03-11 2010-06-08 Takeda Pharmaceutical Company Limited Dipeptidyl peptidase inhibitors
US7393847B2 (en) * 2004-03-13 2008-07-01 Boehringer Ingleheim International Gmbh Imidazopyridazinediones, their preparation and their use as pharmaceutical compositions
CN102127057A (en) * 2004-03-15 2011-07-20 武田药品工业株式会社 Dipeptidyl peptidase inhibitors
WO2005097798A1 (en) * 2004-04-10 2005-10-20 Boehringer Ingelheim International Gmbh Novel 2-amino-imidazo[4,5-d]pyridazin-4-ones and 2-amino-imidazo[4,5-c]pyridin-4-ones, production and use thereof as medicaments
US7179809B2 (en) * 2004-04-10 2007-02-20 Boehringer Ingelheim International Gmbh 2-Amino-imidazo[4,5-d]pyridazin-4-ones, their preparation and their use as pharmaceutical compositions
US7439370B2 (en) 2004-05-10 2008-10-21 Boehringer Ingelheim International Gmbh Imidazole derivatives, their preparation and their use as intermediates for the preparation of pharmaceutical compositions and pesticides
EP1753730A1 (en) * 2004-06-04 2007-02-21 Takeda Pharmaceutical Company Limited Dipeptidyl peptidase inhibitors
DE102004030502A1 (en) 2004-06-24 2006-01-12 Boehringer Ingelheim Pharma Gmbh & Co. Kg Novel imidazoles and triazoles, their preparation and use as medicines
WO2006019965A2 (en) 2004-07-16 2006-02-23 Takeda San Diego, Inc. Dipeptidyl peptidase inhibitors
FR2874014B1 (en) * 2004-08-03 2010-05-14 Univ Paris Descartes ANALOGUES OF AMINOGLYCOSIDES, THEIR USE AND THEIR SYNTHESIS
DE102004037554A1 (en) * 2004-08-03 2006-03-16 Sanofi-Aventis Deutschland Gmbh Substituted 8-aminoalkylthio-xanthines, process for their preparation and their use as medicaments
DE102004038270A1 (en) * 2004-08-06 2006-03-16 Sanofi-Aventis Deutschland Gmbh Substituted bicyclic 8-amino-xanthines, process for their preparation and their use as medicaments
DE102004038268A1 (en) * 2004-08-06 2006-03-16 Sanofi-Aventis Deutschland Gmbh Substituted, bicyclic 8-pyrrolidino-xanthines, process for their preparation and their use as medicaments
DE102004038269A1 (en) * 2004-08-06 2006-03-16 Sanofi-Aventis Deutschland Gmbh Substituted bicyclic 8-piperidino-xanthines, process for their preparation and their use as pharmaceuticals
DE102004039507A1 (en) 2004-08-14 2006-03-02 Sanofi-Aventis Deutschland Gmbh Substituted 8-aminoalkoxi-xanthines, process for their preparation and their use as medicaments
DE102004043944A1 (en) * 2004-09-11 2006-03-30 Boehringer Ingelheim Pharma Gmbh & Co. Kg Novel 8- (3-amino-piperidin-1-yl) -7- (but-2-ynyl) -xanthines, their preparation and their use as pharmaceuticals
DE102004044221A1 (en) * 2004-09-14 2006-03-16 Boehringer Ingelheim Pharma Gmbh & Co. Kg New 3-methyl-7-butynyl xanthines, their preparation and their use as pharmaceuticals
WO2006030847A1 (en) * 2004-09-17 2006-03-23 Dainippon Sumitomo Pharma Co., Ltd. Novel bicyclic pyrazole derivative
DE102004054054A1 (en) * 2004-11-05 2006-05-11 Boehringer Ingelheim Pharma Gmbh & Co. Kg Process for preparing chiral 8- (3-amino-piperidin-1-yl) -xanthines
AU2012205240B2 (en) * 2004-11-05 2015-03-26 Boehringer Ingelheim International Gmbh Method for producing chiral 8-(3-amino-piperidin-1-yl)-xanthines
JP2008524331A (en) 2004-12-21 2008-07-10 武田薬品工業株式会社 Dipeptidyl peptidase inhibitor
KR20070090206A (en) * 2004-12-24 2007-09-05 다이닛본 스미토모 세이야꾸 가부시끼가이샤 Bicyclic pyrrole derivatives
DOP2006000008A (en) * 2005-01-10 2006-08-31 Arena Pharm Inc COMBINED THERAPY FOR THE TREATMENT OF DIABETES AND RELATED AFFECTIONS AND FOR THE TREATMENT OF AFFECTIONS THAT IMPROVE THROUGH AN INCREASE IN THE BLOOD CONCENTRATION OF GLP-1
WO2006112331A1 (en) * 2005-04-13 2006-10-26 Dainippon Simitomo Pharma Co., Ltd. Novel condensed pyrrole derivative
WO2006116157A2 (en) * 2005-04-22 2006-11-02 Alantos Pharmaceuticals Holding, Inc. Dipeptidyl peptidase-iv inhibitors
MY152185A (en) 2005-06-10 2014-08-29 Novartis Ag Modified release 1-[(3-hydroxy-adamant-1-ylamino)-acetyl]-pyrrolidine-2(s)-carbonitrile formulation
DE102005035891A1 (en) 2005-07-30 2007-02-08 Boehringer Ingelheim Pharma Gmbh & Co. Kg 8- (3-amino-piperidin-1-yl) -xanthines, their preparation and their use as pharmaceuticals
KR20080038396A (en) 2005-08-10 2008-05-06 스미스클라인 비참 코포레이션 Xanthine derivatives as selective hm74a agonists
WO2007033266A2 (en) * 2005-09-14 2007-03-22 Takeda Pharmaceutical Company Limited Dipeptidyl peptidase inhibitors for treating diabetis
PE20070622A1 (en) * 2005-09-14 2007-08-22 Takeda Pharmaceutical ADMINISTRATION OF DIPEPTIDYL PEPTIDASE INHIBITORS
ZA200802857B (en) 2005-09-14 2009-09-30 Takeda Pharmaceutical Dipeptidyl peptidase inhibitors for treating diabetes
TW200745080A (en) * 2005-09-16 2007-12-16 Takeda Pharmaceuticals Co Polymorphs of tartrate salt of 2-[2-(3-(R)-amino-piperidin-1-yl)-5-fluoro-6-oxo-6H-pyrimidin-1-ylmethyl]-benzonitrile and methods of use therefor
KR101368988B1 (en) 2005-09-16 2014-02-28 다케다 야쿠힌 고교 가부시키가이샤 Dipeptidyl peptidase inhibitors
TW200745079A (en) * 2005-09-16 2007-12-16 Takeda Pharmaceuticals Co Polymorphs of benzoate salt of 2-[[6-[(3R)-3-amino-1-piperidinyl]-3,4-dihydro-3-methyl-2,4-dioxo-1(2H)-pyrimidinyl]methyl]-benzonitrile and methods of use therefor
GB0526291D0 (en) 2005-12-23 2006-02-01 Prosidion Ltd Therapeutic method
CA2632021A1 (en) * 2005-12-23 2007-06-28 Astrazeneca Ab Gaba-b receptor modulators
JP5302012B2 (en) * 2006-03-08 2013-10-02 タケダ カリフォルニア インコーポレイテッド Glucokinase activator
WO2007112347A1 (en) 2006-03-28 2007-10-04 Takeda Pharmaceutical Company Limited Dipeptidyl peptidase inhibitors
JP2009531456A (en) * 2006-03-28 2009-09-03 武田薬品工業株式会社 Preparation of (R) -3-aminopiperidine dihydrochloride
PL1971862T3 (en) * 2006-04-11 2011-04-29 Arena Pharm Inc Methods of using gpr119 receptor to identify compounds useful for increasing bone mass in an individual
PE20071221A1 (en) 2006-04-11 2007-12-14 Arena Pharm Inc GPR119 RECEPTOR AGONISTS IN METHODS TO INCREASE BONE MASS AND TO TREAT OSTEOPOROSIS AND OTHER CONDITIONS CHARACTERIZED BY LOW BONE MASS, AND COMBINED THERAPY RELATED TO THESE AGONISTS
EP1852108A1 (en) 2006-05-04 2007-11-07 Boehringer Ingelheim Pharma GmbH & Co.KG DPP IV inhibitor formulations
NZ619413A (en) 2006-05-04 2015-08-28 Boehringer Ingelheim Int Polymorphs of a dpp-iv enzyme inhibitor
PE20110235A1 (en) 2006-05-04 2011-04-14 Boehringer Ingelheim Int PHARMACEUTICAL COMBINATIONS INCLUDING LINAGLIPTIN AND METMORPHINE
WO2008017670A1 (en) 2006-08-08 2008-02-14 Boehringer Ingelheim International Gmbh Pyrrolo [3, 2 -d] pyrimidines as dpp-iv inhibitors for the treatment of diabetes mellitus
AR062760A1 (en) * 2006-09-13 2008-12-03 Takeda Pharmaceutical ADMINISTRATION OF DIPEPTIDILPETIDASA INHIBITORS
US8324383B2 (en) 2006-09-13 2012-12-04 Takeda Pharmaceutical Company Limited Methods of making polymorphs of benzoate salt of 2-[[6-[(3R)-3-amino-1-piperidinyl]-3,4-dihydro-3-methyl-2,4-dioxo-1(2H)-pyrimidinyl]methyl]-benzonitrile
US8604244B2 (en) 2010-07-02 2013-12-10 Reviva Pharmaceuticals, Inc. Compositions, synthesis, and methods of using cycloalkylmethylamine derivatives
US7989500B2 (en) 2006-09-15 2011-08-02 Reviva Pharmaceuticals, Inc. Synthesis, methods of using, and compositions of cycloalkylmethylamines
MX2009003548A (en) 2006-10-03 2009-04-15 Alnylam Pharmaceuticals Inc Lipid containing formulations.
TW200838536A (en) * 2006-11-29 2008-10-01 Takeda Pharmaceutical Polymorphs of succinate salt of 2-[6-(3-amino-piperidin-1-yl)-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethy]-4-fluor-benzonitrile and methods of use therefor
EP1939197A1 (en) * 2006-12-22 2008-07-02 Schwarz Pharma Ag 8-ethinylxanthine derivatives as selective A2A receptor antagonists
WO2008103615A1 (en) * 2007-02-21 2008-08-28 Kalypsys, Inc. Isoquinolines useful as inducible nitric oxide synthase inhibitors
US8093236B2 (en) 2007-03-13 2012-01-10 Takeda Pharmaceuticals Company Limited Weekly administration of dipeptidyl peptidase inhibitors
CL2008002427A1 (en) 2007-08-16 2009-09-11 Boehringer Ingelheim Int Pharmaceutical composition comprising 1-chloro-4- (bd-glucopyranos-1-yl) -2- [4 - ((s) -tetrahydrofuran-3-yloxy) benzyl] -benzene combined with 1 - [(4-methylquinazolin- 2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3- (r) -aminopiperidin-1-yl) xanthine; and its use to treat type 2 diabetes mellitus.
ES2733348T3 (en) 2007-08-17 2019-11-28 Boehringer Ingelheim Int Purine derivatives for use in the treatment of diseases related to FAP
WO2009037719A1 (en) * 2007-09-21 2009-03-26 Lupin Limited Novel compounds as dipeptidyl peptidase iv (dpp iv) inhibitors
US8138168B1 (en) 2007-09-26 2012-03-20 Takeda Pharmaceutical Company Limited Renin inhibitors
EP2222676A4 (en) * 2007-12-21 2011-10-26 Endacea Inc A1 adenosine receptor antagonists
CN101952252A (en) * 2008-02-27 2011-01-19 住友化学株式会社 Method for optical resolution of alkylpiperidin-3-yl carbamate and intermediate therefor
JP2009256298A (en) * 2008-03-26 2009-11-05 Sumitomo Chemical Co Ltd Optical resolution method for piperidin-3-ylcarbamate compound, and its intermediate
JP2009256337A (en) * 2008-03-26 2009-11-05 Sumitomo Chemical Co Ltd Method for producing piperidin-3-ylcarbamate compound
AR071175A1 (en) 2008-04-03 2010-06-02 Boehringer Ingelheim Int PHARMACEUTICAL COMPOSITION THAT INCLUDES AN INHIBITOR OF DIPEPTIDIL-PEPTIDASA-4 (DPP4) AND A COMPARING PHARMACO
EP2146210A1 (en) 2008-04-07 2010-01-20 Arena Pharmaceuticals, Inc. Methods of using A G protein-coupled receptor to identify peptide YY (PYY) secretagogues and compounds useful in the treatment of conditions modulated by PYY
WO2010039289A2 (en) 2008-05-14 2010-04-08 Hydra Biosciences, Inc. Compounds and compositions for treating chemical warfare agent-induced injuries
WO2009140517A1 (en) 2008-05-14 2009-11-19 Hydra Biosciences, Inc. Compounds and compositions for treating chemical warfare agent-induced injuries
PE20100156A1 (en) * 2008-06-03 2010-02-23 Boehringer Ingelheim Int NAFLD TREATMENT
KR20190016601A (en) 2008-08-06 2019-02-18 베링거 인겔하임 인터내셔날 게엠베하 Treatment for diabetes in patients inappropriate for metformin therapy
UY32030A (en) 2008-08-06 2010-03-26 Boehringer Ingelheim Int "TREATMENT FOR DIABETES IN INAPPROPRIATE PATIENTS FOR THERAPY WITH METFORMIN"
CA2735562C (en) 2008-08-15 2017-10-17 Boehringer Ingelheim International Gmbh Dpp-4 inhibitors for wound healing
RU2011113823A (en) 2008-09-10 2012-10-20 БЕРИНГЕР ИНГЕЛЬХАЙМ ИНТЕРНАЦИОНАЛЬ ГмбХ (DE) COMBINED THERAPY FOR THE TREATMENT OF DIABETES AND RELATED CONDITIONS
US20200155558A1 (en) 2018-11-20 2020-05-21 Boehringer Ingelheim International Gmbh Treatment for diabetes in patients with insufficient glycemic control despite therapy with an oral antidiabetic drug
JP2012512848A (en) 2008-12-23 2012-06-07 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング Salt forms of organic compounds
AR074990A1 (en) 2009-01-07 2011-03-02 Boehringer Ingelheim Int TREATMENT OF DIABETES IN PATIENTS WITH AN INAPPROPRIATE GLUCEMIC CONTROL THROUGH METFORMIN THERAPY
AR075204A1 (en) 2009-01-29 2011-03-16 Boehringer Ingelheim Int DPP-4 INHIBITORS AND PHARMACEUTICAL COMPOSITIONS THAT INCLUDE THEM, USEFUL TO TREAT METABOLIC DISEASES IN PEDIATRIC PATIENTS, PARTICULARLY MELLITUS DIABETES TYPE 2
NZ594044A (en) 2009-02-13 2014-08-29 Boehringer Ingelheim Int Antidiabetic medications comprising a dpp-4 inhibitor (linagliptin) optionally in combination with other antidiabetics
PL2395983T3 (en) 2009-02-13 2020-09-07 Boehringer Ingelheim International Gmbh Pharmaceutical composition comprisng a sglt2 inhibitor, a dpp-iv inhibitor and optionally a further antidiabetic agent and uses thereof
WO2010132838A1 (en) * 2009-05-14 2010-11-18 Hydra Biosciences, Inc. Compounds useful for treating disorders related to trpa1
US8748457B2 (en) 2009-06-18 2014-06-10 Lupin Limited 2-amino-2- [8-(dimethyl carbamoyl)- 8-aza- bicyclo [3.2.1] oct-3-yl]-exo- ethanoyl derivatives as potent DPP-IV inhibitors
AR077642A1 (en) 2009-07-09 2011-09-14 Arena Pharm Inc METABOLISM MODULATORS AND THE TREATMENT OF DISORDERS RELATED TO THE SAME
EA030999B1 (en) 2009-10-02 2018-10-31 Бёрингер Ингельхайм Интернациональ Гмбх Use of a pharmaceutical composition comprising a dpp-4 inhibitor and metformin hydrochloride
JP2013512229A (en) 2009-11-27 2013-04-11 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング Treatment of diabetic patients whose genotype has been identified with DDP-IV inhibitors such as linagliptin
WO2011113947A1 (en) 2010-03-18 2011-09-22 Boehringer Ingelheim International Gmbh Combination of a gpr119 agonist and the dpp-iv inhibitor linagliptin for use in the treatment of diabetes and related conditions
EP2368552A1 (en) 2010-03-25 2011-09-28 Boehringer Ingelheim Vetmedica GmbH 1-[(3-cyano-pyridin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(r)-amino-piperidin-1-yl]-xanthine for the treatment of a metabolic disorder of a predominantly carnivorous non-human animal
MX2012011631A (en) 2010-04-06 2013-01-18 Arena Pharm Inc Modulators of the gpr119 receptor and the treatment of disorders related thereto.
CN102276627B (en) * 2010-04-29 2013-07-31 山东轩竹医药科技有限公司 Pyridino-heterocycle derivative
BR112012028136A2 (en) 2010-05-05 2016-08-09 Boehringer Ingelheim Int combination therapy
AU2011249771A1 (en) 2010-05-05 2012-11-01 Boehringer Ingelheim International Gmbh Pharmaceutical formulations comprising pioglitazone and linagliptin
EP3725325B1 (en) 2010-06-24 2023-05-31 Boehringer Ingelheim International GmbH Diabetes therapy
JP5827998B2 (en) * 2010-09-13 2015-12-02 アドヴィナス・セラピューティックス・リミテッド Purine compounds as prodrugs of A2B adenosine receptor antagonists, application of these methods and agents
CA2812061A1 (en) 2010-09-22 2012-03-29 Arena Pharmaceuticals, Inc. Modulators of the gpr119 receptor and the treatment of disorders related thereto
US9034883B2 (en) 2010-11-15 2015-05-19 Boehringer Ingelheim International Gmbh Vasoprotective and cardioprotective antidiabetic therapy
AR085689A1 (en) 2011-03-07 2013-10-23 Boehringer Ingelheim Int PHARMACEUTICAL COMPOSITIONS OF METFORMIN, LINAGLIPTINE AND AN SGLT-2 INHIBITOR
WO2012135570A1 (en) 2011-04-01 2012-10-04 Arena Pharmaceuticals, Inc. Modulators of the gpr119 receptor and the treatment of disorders related thereto
US20140066369A1 (en) 2011-04-19 2014-03-06 Arena Pharmaceuticals, Inc. Modulators Of The GPR119 Receptor And The Treatment Of Disorders Related Thereto
US20140038889A1 (en) 2011-04-22 2014-02-06 Arena Pharmaceuticals, Inc. Modulators Of The GPR119 Receptor And The Treatment Of Disorders Related Thereto
WO2012145604A1 (en) 2011-04-22 2012-10-26 Arena Pharmaceuticals, Inc. Modulators of the gpr119 receptor and the treatment of disorders related thereto
WO2012170702A1 (en) 2011-06-08 2012-12-13 Arena Pharmaceuticals, Inc. Modulators of the gpr119 receptor and the treatment of disorders related thereto
CN103781788B (en) 2011-07-15 2016-08-17 勃林格殷格翰国际有限公司 Quinazoline, its preparation and the purposes in pharmaceutical composition thereof being substituted
RU2014109079A (en) 2011-08-12 2015-09-20 Бёрингер Ингельхайм Ветмедика Гмбх PHARMACEUTICAL COMPOSITION WITH MASKED TASTE
WO2013055910A1 (en) 2011-10-12 2013-04-18 Arena Pharmaceuticals, Inc. Modulators of the gpr119 receptor and the treatment of disorders related thereto
US20130172244A1 (en) 2011-12-29 2013-07-04 Thomas Klein Subcutaneous therapeutic use of dpp-4 inhibitor
IN2014MN01407A (en) 2011-12-30 2015-07-03 Reviva Pharmaceuticals Inc
US9555001B2 (en) 2012-03-07 2017-01-31 Boehringer Ingelheim International Gmbh Pharmaceutical composition and uses thereof
EP3685839A1 (en) 2012-05-14 2020-07-29 Boehringer Ingelheim International GmbH Linagliptin for use in the treatment of albuminuria and kidney related diseases
EP4151218A1 (en) 2012-05-14 2023-03-22 Boehringer Ingelheim International GmbH Linagliptin, a xanthine derivative as dpp-4 inhibitor, for use in the treatment of sirs and/or sepsis
WO2013174768A1 (en) 2012-05-24 2013-11-28 Boehringer Ingelheim International Gmbh A xanthine derivative as dpp -4 inhibitor for use in the treatment of autoimmune diabetes, particularly lada
WO2013174767A1 (en) 2012-05-24 2013-11-28 Boehringer Ingelheim International Gmbh A xanthine derivative as dpp -4 inhibitor for use in modifying food intake and regulating food preference
JP2015518843A (en) 2012-05-25 2015-07-06 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング Use of keratinocytes as bioactive agents that may be combined with DPP-4 inhibitors in the treatment of wounds, for example diabetic wounds
CN103509022B (en) * 2012-06-20 2015-04-01 成都苑东药业有限公司 Xanthine derivative
CN103509023B (en) * 2012-06-20 2014-08-27 成都苑东药业有限公司 Xanthine derivative
US20150246117A1 (en) 2012-09-24 2015-09-03 Ulf Eriksson Treatment of type 2 diabetes and related conditions
WO2014074668A1 (en) 2012-11-08 2014-05-15 Arena Pharmaceuticals, Inc. Modulators of gpr119 and the treatment of disorders related thereto
CN106008507B (en) * 2013-01-23 2017-11-28 成都苑东生物制药股份有限公司 Xanthine derivative
CN103936738B (en) * 2013-01-23 2016-11-23 成都苑东生物制药股份有限公司 Xanthine derivative
CA2899646C (en) 2013-03-15 2021-08-31 Hydra Biosciences, Inc. Substituted xanthines and methods of use thereof
CN110075098A (en) 2013-03-15 2019-08-02 勃林格殷格翰国际有限公司 Purposes of the Li Gelieting in heart and protection renal antidiabetic treatment
US11813275B2 (en) 2013-04-05 2023-11-14 Boehringer Ingelheim International Gmbh Pharmaceutical composition, methods for treating and uses thereof
US20140303097A1 (en) 2013-04-05 2014-10-09 Boehringer Ingelheim International Gmbh Pharmaceutical composition, methods for treating and uses thereof
ES2702174T3 (en) 2013-04-05 2019-02-27 Boehringer Ingelheim Int Therapeutic uses of empagliflozin
PT2986304T (en) 2013-04-18 2022-02-25 Boehringer Ingelheim Int Pharmaceutical composition, methods for treating and uses thereof
CN104211702B (en) * 2013-05-29 2018-08-31 中国医学科学院药物研究所 Substituted xanthine class compound and its preparation method and application
CN104292228B (en) * 2013-07-16 2016-03-30 成都苑东生物制药股份有限公司 Polymorphic of a kind of Xanthine compounds and preparation method thereof, purposes
PT3539965T (en) 2013-12-09 2021-04-07 Unichem Lab Ltd An improved process for the preparation of (3r,4r)-(1-benzyl-4-methylpiperidin-3-yl)-methylamine
EP3110449B1 (en) 2014-02-28 2023-06-28 Boehringer Ingelheim International GmbH Medical use of a dpp-4 inhibitor
CN105646492B (en) * 2014-11-14 2019-04-09 中国医学科学院药物研究所 Substituted xanthine class compound and its preparation method and application containing five yuan of heteroaromatics
EA201791982A1 (en) 2015-03-09 2020-02-17 Интекрин Терапьютикс, Инк. METHODS FOR TREATING A NON-ALCOHOLIC FAT LIVER DISEASE AND / OR LIPODYSTROPHY
CN107709323B (en) 2015-05-20 2020-11-20 广东众生睿创生物科技有限公司 Hydroxyl purine compound and application thereof
WO2016184313A1 (en) 2015-05-20 2016-11-24 南京明德新药研发股份有限公司 Hydroxyl purine compounds and use thereof
MX2018015089A (en) 2016-06-10 2019-05-13 Boehringer Ingelheim Int Combinations of linagliptin and metformin.
WO2018104263A1 (en) 2016-12-06 2018-06-14 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods of enhancing the potency of incretin-based drugs in subjects in need thereof
WO2018162722A1 (en) 2017-03-09 2018-09-13 Deutsches Institut Für Ernährungsforschung Potsdam-Rehbrücke Dpp-4 inhibitors for use in treating bone fractures
EP3606527A1 (en) 2017-04-03 2020-02-12 Coherus Biosciences, Inc. Ppar-gamma agonist for treatment of progressive supranuclear palsy
UA124793C2 (en) * 2017-07-11 2021-11-17 Берінґер Інґельгайм Інтернаціональ Ґмбг Novel substituted xanthine derivatives
SG11202003664TA (en) 2017-11-30 2020-05-28 Arrakis Therapeutics Inc Nucleic acid-binding photoprobes and uses thereof
CN114727983A (en) * 2019-09-25 2022-07-08 金翅雀生物公司 Xanthine CB1 inhibitors
CN112898303A (en) * 2019-12-04 2021-06-04 江苏正大清江制药有限公司 Synthetic method of linagliptin chloro intermediate
CN112007032B (en) * 2020-09-16 2021-10-22 厦门大学 Application of compound in preparation of small molecule inhibitor or cancer treatment drug, small molecule inhibitor and cancer treatment drug
WO2023023867A1 (en) * 2021-08-26 2023-03-02 Mcmaster University Compounds for reducing cholesterol and treating liver and kidney disease
WO2024091863A1 (en) 2022-10-25 2024-05-02 Starrock Pharma Llc Combinatorial, and rotational combinatorial therapies for obesity and other diseases

Family Cites Families (110)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2056046A (en) * 1933-05-19 1936-09-29 Rhone Poulenc Sa Manufacture of bases derived from benz-dioxane
US2223499A (en) * 1936-08-20 1940-12-03 Crown Cork & Seal Co Method of coating metal
US2375138A (en) * 1942-05-01 1945-05-01 American Cyanamid Co Alkamine esters of aryloxymethyl benzoic acid
US2629736A (en) * 1951-02-24 1953-02-24 Searle & Co Basically substituted n-alkyl derivatives of alpha, beta, beta-triarylpropionamides
US2730544A (en) * 1952-07-23 1956-01-10 Sahyun Lab Alkylaminoalkyl esters of hydroxycyclohexylbenzoic acid
US2750387A (en) * 1953-11-25 1956-06-12 Searle & Co Basically substituted derivatives of diarylaminobenzamides
DE1211359B (en) * 1955-11-29 1966-02-24 Oreal Oxidant-free cold dye for human hair
US2928833A (en) * 1959-03-03 1960-03-15 S E Massengill Company Theophylline derivatives
US3174901A (en) * 1963-01-31 1965-03-23 Jan Marcel Didier Aron Samuel Process for the oral treatment of diabetes
US3454635A (en) * 1965-07-27 1969-07-08 Hoechst Ag Benzenesulfonyl-ureas and process for their manufacture
US3673241A (en) * 1968-04-04 1972-06-27 Ciba Geigy Corp Substituted benzaldehyde guanylhydrazones
JPS5512435B2 (en) * 1972-07-01 1980-04-02
US4005208A (en) * 1975-05-16 1977-01-25 Smithkline Corporation N-Heterocyclic-9-xanthenylamines
US4061753A (en) * 1976-02-06 1977-12-06 Interx Research Corporation Treating psoriasis with transient pro-drug forms of xanthine derivatives
US4397779A (en) * 1978-08-09 1983-08-09 Baxter Travenol Laboratories, Inc. Preparation of xanthine tracers
PH23995A (en) * 1984-01-09 1990-02-09 Janssen Pharmaceutica Nv 4((bicycle heterocyclyl)-methyl and hetero)piperidines
FR2558162B1 (en) * 1984-01-17 1986-04-25 Adir NOVEL XANTHINE DERIVATIVES, PROCESSES FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
FI79107C (en) * 1984-06-25 1989-11-10 Orion Yhtymae Oy Process for the preparation of stable form of prazosin hydrochloride.
AR240698A1 (en) * 1985-01-19 1990-09-28 Takeda Chemical Industries Ltd Process for the preparation of 5-(4-(2-(5-ethyl-2-pyridil)-ethoxy)benzyl)-2,4-thiazolodinedione and their salts
US5258380A (en) * 1985-06-24 1993-11-02 Janssen Pharmaceutica N.V. (4-piperidinylmethyl and -hetero)purines
GB8515934D0 (en) * 1985-06-24 1985-07-24 Janssen Pharmaceutica Nv (4-piperidinomethyl and-hetero)purines
US4968672A (en) * 1987-01-02 1990-11-06 The United States Of America As Represented By The Department Of Health And Human Services Adenosine receptor prodrugs
US5329025A (en) * 1988-09-21 1994-07-12 G. D. Searle & Co. 3-azido compound
US5234897A (en) * 1989-03-15 1993-08-10 Bayer Aktiengesellschaft Herbicidal 3-amino-5-aminocarbonyl-1,2,4-triazoles
GB8906792D0 (en) * 1989-03-23 1989-05-10 Beecham Wuelfing Gmbh & Co Kg Treatment and compounds
DE3916430A1 (en) * 1989-05-20 1990-11-22 Bayer Ag METHOD FOR PRODUCING 3-AMINO-5-AMINOCARBONYL-1,2,4-TRIAZOLE DERIVATIVES
US5223499A (en) * 1989-05-30 1993-06-29 Merck & Co., Inc. 6-amino substituted imidazo[4,5-bipyridines as angiotensin II antagonists
US5332744A (en) * 1989-05-30 1994-07-26 Merck & Co., Inc. Substituted imidazo-fused 6-membered heterocycles as angiotensin II antagonists
FR2654935B1 (en) * 1989-11-28 1994-07-01 Lvmh Rech USE OF XANTHINES, WHICH MAY BE INCORPORATED IN LIPOSOMES, TO PROMOTE PIGMENTATION OF THE SKIN OR HAIR.
DK0443983T3 (en) * 1990-02-19 1996-03-18 Ciba Geigy Ag acrylic Compounds
US5084460A (en) * 1990-12-24 1992-01-28 A. H. Robins Company, Incorporated Methods of therapeutic treatment with N-(3-ouinuclidinyl)-2-hydroxybenzamides and thiobenzamides
DE4124150A1 (en) * 1991-07-20 1993-01-21 Bayer Ag SUBSTITUTED TRIAZOLES
US5484920A (en) * 1992-04-08 1996-01-16 Kyowa Hakko Kogyo Co., Ltd. Therapeutic agent for Parkinson's disease
US5300298A (en) * 1992-05-06 1994-04-05 The Pennsylvania Research Corporation Methods of treating obesity with purine related compounds
GB9215633D0 (en) * 1992-07-23 1992-09-09 Smithkline Beecham Plc Novel treatment
ES2115725T3 (en) * 1992-07-31 1998-07-01 Shionogi & Co TRIAZOLYLTIOMETHYLETHEOPHALOSPORINE HYDROCHLORIDE, ITS CRYSTALLINE HYDRATE AND THE PREPARATION OF IT.
TW252044B (en) * 1992-08-10 1995-07-21 Boehringer Ingelheim Kg
JP2613355B2 (en) * 1992-09-28 1997-05-28 協和醗酵工業株式会社 Parkinson's disease treatment
DE4242459A1 (en) * 1992-12-16 1994-06-23 Merck Patent Gmbh imidazopyridines
GB9501178D0 (en) * 1995-01-20 1995-03-08 Wellcome Found Guanine derivative
FR2742751B1 (en) * 1995-12-22 1998-01-30 Rhone Poulenc Rorer Sa NOVEL TAXOIDS, THEIR PREPARATION AND THE PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
US5735635A (en) 1996-01-04 1998-04-07 Northern Tier Gardens Corporation Gravity feed watering system for plants
DE19616486C5 (en) * 1996-04-25 2016-06-30 Royalty Pharma Collection Trust Method for lowering the blood glucose level in mammals
US5965555A (en) * 1996-06-07 1999-10-12 Hoechst Aktiengesellschaft Xanthine compounds having terminally animated alkynol side chains
US5958951A (en) * 1996-06-14 1999-09-28 Novo Nordiskials Modified form of the R(-)-N-(4,4-di(3-methylthien-2-yl)but-3-enyl)-nipecotic acid hydrochloride
US5753635A (en) * 1996-08-16 1998-05-19 Berlex Laboratories, Inc. Purine derivatives and their use as anti-coagulants
EP0975608B1 (en) 1997-04-15 2005-06-15 Genentech, Inc. Halo-alkoxycarbonyl prodrugs
AU1791699A (en) * 1997-12-05 1999-06-28 Astrazeneca Uk Limited Novel compounds
CA2315736A1 (en) * 1998-01-05 1999-07-15 Eisai Co., Ltd. Purine compounds and adenosine a2 receptor antagonist as preventive or therapeutic for diabetes mellitus
DE19823831A1 (en) * 1998-05-28 1999-12-02 Probiodrug Ges Fuer Arzneim New pharmaceutical use of isoleucyl thiazolidide and its salts
DE19828114A1 (en) * 1998-06-24 2000-01-27 Probiodrug Ges Fuer Arzneim Produgs of unstable inhibitors of dipeptidyl peptidase IV
IT1312018B1 (en) * 1999-03-19 2002-04-04 Fassi Aldo IMPROVED PROCEDURE FOR THE PRODUCTION OF NON HYGROSCOPICIDAL SALTS OF L (-) - CARNITINE.
MXPA01012899A (en) * 1999-06-21 2002-07-30 Boehringer Ingelheim Pharma Bicyclic heterocycles, medicaments containing these compounds, their use and methods for the production thereof.
US6515117B2 (en) * 1999-10-12 2003-02-04 Bristol-Myers Squibb Company C-aryl glucoside SGLT2 inhibitors and method
AU782878B2 (en) * 2000-02-05 2005-09-08 Vertex Pharmaceuticals Incorporated Pyrazole compositions useful as inhibitors of erk
US6512523B1 (en) * 2000-03-27 2003-01-28 Intel Corporation Accurate averaging of elements using integer averaging
US7078397B2 (en) * 2000-06-19 2006-07-18 Smithkline Beecham Corporation Combinations of dipeptidyl peptidase IV inhibitors and other antidiabetic agents for the treatment of diabetes mellitus
EP1301187B1 (en) * 2000-07-04 2005-07-06 Novo Nordisk A/S Purine-2,6-diones which are inhibitors of the enzyme dipeptidyl peptidase iv (dpp-iv)
BRPI0113146B8 (en) * 2000-08-10 2021-05-25 Mitsubishi Pharma Corp "proline derivatives and pharmaceutical composition comprising them".
US6821978B2 (en) 2000-09-19 2004-11-23 Schering Corporation Xanthine phosphodiesterase V inhibitors
JPWO2002051836A1 (en) * 2000-12-27 2004-04-22 協和醗酵工業株式会社 Dipeptidyl peptidase-IV inhibitor
FR2819254B1 (en) * 2001-01-08 2003-04-18 Fournier Lab Sa NOVEL N- (PHENYLSULFONYL) GLYCINE COMPOUNDS, PROCESS FOR THEIR PREPARATION AND THEIR USE FOR OBTAINING PHARMACEUTICAL COMPOSITIONS
HU230382B1 (en) * 2001-02-24 2016-03-29 Boehringer Ingelheim Pharma Gmbh & Co. Kg Xanthine derivative, production and use thereof as a medicament
US6936590B2 (en) * 2001-03-13 2005-08-30 Bristol Myers Squibb Company C-aryl glucoside SGLT2 inhibitors and method
DE60225556D1 (en) 2001-07-03 2008-04-24 Novo Nordisk As DPP-IV INHIBITING PURINE DERIVATIVE FOR THE TREATMENT OF DIABETES
US6869947B2 (en) * 2001-07-03 2005-03-22 Novo Nordisk A/S Heterocyclic compounds that are inhibitors of the enzyme DPP-IV
US7638522B2 (en) * 2001-08-13 2009-12-29 Janssen Pharmaceutica N.V. Salt of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino] benzonitrile
AU2002331311A1 (en) * 2001-09-19 2003-04-01 Novo Nordisk A/S Heterocyclic compounds that are inhibitors of the enzyme dpp-iv
US6727261B2 (en) * 2001-12-27 2004-04-27 Hoffman-La Roche Inc. Pyrido[2,1-A]Isoquinoline derivatives
JP2005513165A (en) * 2002-01-11 2005-05-12 ノボ　ノルディスク　アクティーゼルスカブ Methods and compositions for the treatment of diabetes, hypertension, chronic heart failure and fluid retention
JP2005517690A (en) * 2002-02-01 2005-06-16 ファイザー・プロダクツ・インク Immediate release dosage form containing solid drug dispersion
DE60304911D1 (en) * 2002-02-25 2006-06-08 Eisai Co Ltd Xanthine derivatives as DPP-IV inhibitors
CN100497336C (en) * 2002-05-31 2009-06-10 先灵公司 Process for preparing xanthine phosphodiesterase V inhibitors and precursors thereof
CN100348599C (en) * 2002-06-06 2007-11-14 卫材R&D管理有限公司 Novel fused imidazole derivative
US20040023981A1 (en) * 2002-07-24 2004-02-05 Yu Ren Salt forms with tyrosine kinase activity
US7407955B2 (en) * 2002-08-21 2008-08-05 Boehringer Ingelheim Pharma Gmbh & Co., Kg 8-[3-amino-piperidin-1-yl]-xanthines, the preparation thereof and their use as pharmaceutical compositions
US7569574B2 (en) * 2002-08-22 2009-08-04 Boehringer Ingelheim Pharma Gmbh & Co. Kg Purine derivatives, the preparation thereof and their use as pharmaceutical compositions
US7495005B2 (en) * 2002-08-22 2009-02-24 Boehringer Ingelheim Pharma Gmbh & Co. Kg Xanthine derivatives, their preparation and their use in pharmaceutical compositions
EP1537880A4 (en) * 2002-09-11 2009-07-01 Takeda Pharmaceutical Sustained release preparation
JP2006503045A (en) * 2002-09-16 2006-01-26 ワイエス Delayed release formulations for oral administration of polypeptide therapeutic agents and methods of using the same
MXPA05003252A (en) * 2002-09-26 2005-07-05 Eisai Co Ltd Combination drug.
US7482337B2 (en) * 2002-11-08 2009-01-27 Boehringer Ingelheim Pharma Gmbh & Co. Kg Xanthine derivatives, the preparation thereof and their use as pharmaceutical compositions
DE10254304A1 (en) * 2002-11-21 2004-06-03 Boehringer Ingelheim Pharma Gmbh & Co. Kg New xanthine derivatives, their production and their use as medicines
US7109192B2 (en) * 2002-12-03 2006-09-19 Boehringer Ingelheim Pharma Gmbh & Co Kg Substituted imidazo-pyridinones and imidazo-pyridazinones, the preparation thereof and their use as pharmaceutical compositions
DE10335027A1 (en) * 2003-07-31 2005-02-17 Boehringer Ingelheim Pharma Gmbh & Co. Kg Use of telmisartan and simvastatin for treatment or prophylaxis of cardiovascular, cardiopulmonary and renal diseases e.g. hypertension combined with hyperlipidemia or atherosclerosis
US7566707B2 (en) * 2003-06-18 2009-07-28 Boehringer Ingelheim International Gmbh Imidazopyridazinone and imidazopyridone derivatives, the preparation thereof and their use as pharmaceutical compositions
JO2625B1 (en) * 2003-06-24 2011-11-01 ميرك شارب اند دوم كوربوريشن Phosphoric acid salt of a dipeptidyl peptidase-IV inhibitor
DE10355304A1 (en) * 2003-11-27 2005-06-23 Boehringer Ingelheim Pharma Gmbh & Co. Kg Novel 8- (piperazin-1-yl) and 8 - ([1,4] diazepan-1-yl) xanthines, their preparation and their use as pharmaceuticals
WO2005053695A1 (en) * 2003-12-04 2005-06-16 Eisai Co., Ltd. Preventive or therapeutic agent for multiple sclerosis
US7217711B2 (en) * 2003-12-17 2007-05-15 Boehringer Ingelheim International Gmbh Piperazin-1-yl and 2-([1,4]diazepan-1-yl)-imidazo[4,5-d]-pyridazin-4-ones, the preparation thereof and their use as pharmaceutical compositions
DK1723136T3 (en) * 2003-12-18 2011-06-27 Tibotec Pharm Ltd Piperidinamino benzimidazole derivative as inhibitors of respiratory syncytial virus replication
DE10360835A1 (en) * 2003-12-23 2005-07-21 Boehringer Ingelheim Pharma Gmbh & Co. Kg New bicyclic imidazole derivatives are dipeptidylpeptidase-IV inhibitors useful to treat e.g. arthritis, obesity, allograft transplantation and calcitonin-induced osteoporosis
US7501426B2 (en) * 2004-02-18 2009-03-10 Boehringer Ingelheim International Gmbh 8-[3-amino-piperidin-1-yl]-xanthines, their preparation and their use as pharmaceutical compositions
DE102004009039A1 (en) * 2004-02-23 2005-09-08 Boehringer Ingelheim Pharma Gmbh & Co. Kg 8- [3-Amino-piperidin-1-yl] xanthines, their preparation and use as pharmaceuticals
US7393847B2 (en) * 2004-03-13 2008-07-01 Boehringer Ingleheim International Gmbh Imidazopyridazinediones, their preparation and their use as pharmaceutical compositions
US7179809B2 (en) * 2004-04-10 2007-02-20 Boehringer Ingelheim International Gmbh 2-Amino-imidazo[4,5-d]pyridazin-4-ones, their preparation and their use as pharmaceutical compositions
US20050239778A1 (en) * 2004-04-22 2005-10-27 Boehringer Ingelheim International Gmbh Novel medicament combinations for the treatment of respiratory diseases
US7439370B2 (en) * 2004-05-10 2008-10-21 Boehringer Ingelheim International Gmbh Imidazole derivatives, their preparation and their use as intermediates for the preparation of pharmaceutical compositions and pesticides
ATE437870T1 (en) * 2004-05-12 2009-08-15 Pfizer Prod Inc PROLINE DERIVATIVES AND THEIR USE AS DIPEPTIDYLPEPTIDASE IV INHIBITORS
TWI354569B (en) * 2004-05-28 2011-12-21 Bristol Myers Squibb Co Coated tablet formulation and method
DE102004030502A1 (en) * 2004-06-24 2006-01-12 Boehringer Ingelheim Pharma Gmbh & Co. Kg Novel imidazoles and triazoles, their preparation and use as medicines
US6980431B1 (en) * 2004-06-30 2005-12-27 Shuttle Inc. Controlling device for controlling slot shutter
TW200613275A (en) * 2004-08-24 2006-05-01 Recordati Ireland Ltd Lercanidipine salts
DE102004043944A1 (en) * 2004-09-11 2006-03-30 Boehringer Ingelheim Pharma Gmbh & Co. Kg Novel 8- (3-amino-piperidin-1-yl) -7- (but-2-ynyl) -xanthines, their preparation and their use as pharmaceuticals
DE102004044221A1 (en) * 2004-09-14 2006-03-16 Boehringer Ingelheim Pharma Gmbh & Co. Kg New 3-methyl-7-butynyl xanthines, their preparation and their use as pharmaceuticals
DE102004054054A1 (en) * 2004-11-05 2006-05-11 Boehringer Ingelheim Pharma Gmbh & Co. Kg Process for preparing chiral 8- (3-amino-piperidin-1-yl) -xanthines
DOP2006000008A (en) * 2005-01-10 2006-08-31 Arena Pharm Inc COMBINED THERAPY FOR THE TREATMENT OF DIABETES AND RELATED AFFECTIONS AND FOR THE TREATMENT OF AFFECTIONS THAT IMPROVE THROUGH AN INCREASE IN THE BLOOD CONCENTRATION OF GLP-1
EP1883631A1 (en) * 2005-05-25 2008-02-06 Wyeth Methods of synthesizing substituted 3-cyanoquinolines and intermediates thereof
DE102005035891A1 (en) * 2005-07-30 2007-02-08 Boehringer Ingelheim Pharma Gmbh & Co. Kg 8- (3-amino-piperidin-1-yl) -xanthines, their preparation and their use as pharmaceuticals
PE20110235A1 (en) * 2006-05-04 2011-04-14 Boehringer Ingelheim Int PHARMACEUTICAL COMBINATIONS INCLUDING LINAGLIPTIN AND METMORPHINE

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