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CA2505389A1 - 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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CA2505389A1
CA2505389A1 CA002505389A CA2505389A CA2505389A1 CA 2505389 A1 CA2505389 A1 CA 2505389A1 CA 002505389 A CA002505389 A CA 002505389A CA 2505389 A CA2505389 A CA 2505389A CA 2505389 A1 CA2505389 A1 CA 2505389A1
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alkyl
benzo
amino
methyl
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CA2505389C (en
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Frank Himmelsbach
Elke Langkopf
Matthias Eckhardt
Roland Maier
Michael Mark
Mohammad Tadayyon
Ralf R. H. Lotz
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Boehringer Ingelheim Pharma GmbH and Co KG
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D473/00—Heterocyclic compounds containing purine ring systems
    • C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
    • A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin

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Abstract

The present invention relates to substituted xanthines of general formula (see formula I), wherein R1 to R4 are defined as in claim 1, the tautomers, the stereoisomers, the mixtures thereof, the prodrugs thereof and the salts thereof, which have valuable pharmacological properties, particularly an inhibitory effect on the activity of the enzyme dipeptidylpeptidase-IV (DPP-IV).

Claims (10)

1. Compounds of general formula wherein R1 denotes a C1-3-alkyl group substituted by a group R a, while R a denotes a 1,4-dihydro-quinazolinyl or 3,4-dihydro-quinazolinyl group wherein in each case in the benzo moiety one to three methyne groups may be replaced by nitrogen atoms, a 3,4-dihydro-isoquinolinyl, 1H-benzo[d][1,2]oxazinyl, 4H-benzo[e][1,3]oxazinyl, 4H-benzo[d][1,3]oxazinyl or 2H-benzo[1,4]oxazinyl group, wherein in each case in the benzo moiety one to three methyne groups may be replaced by nitrogen atoms and in the heterocyclyl moiety a methylene group may be replaced by a carbonyl group, a 4H-benzo[e][1,3]thiazinyl, 4H-benzo[d][1,3]thiazinyl or 2H-benzo[1,4]thiazinyl group, wherein in each case in the benzo moiety one to three methyne groups may be replaced by nitrogen atoms and in the heterocyclyl moiety a methylene group may be replaced by a carbonyl group and a sulphur atom may be replaced by a sulphinyl or sulphonyl group, a 2-oxo-2H-benzo[e][1,3]oxazinyl or 2,2-dioxo-1H-benzo[c][1,2]thiazinyl group, wherein in each case in the benzo moiety one to three methyne groups may be replaced by nitrogen atoms, a 2,3-dihydro-1H-benzo[e][1,4]diazepinyl, 4,5-dihydro-3H-benzo[b]-[1,4]diazepinyl or 5-oxo-4,5-dihydro-3H-benzo[e][1,4]diazepinyl group, wherein in each case in the benzo moiety one to three methyne groups may be replaced by nitrogen atoms and in the heterocyclyl moiety a methylene group may be replaced by a carbonyl group , a 2,3-dihydro-benzo[f][1,4]oxazepinyl or 2,3-dihydro-benzo[b][1,4]oxa-zepinyl group wherein in each case in the benzo moiety one to three methyne groups may be replaced by nitrogen atoms and in the heterocyclyl moiety a methylene group may be replaced by a carbonyl group, a 2,3-dihydro-benzo[f][1,4]thiazepinyl or 2,3-dihydro-benzo[b][1,4]thiazepinyl group, wherein in each case in the benzo moiety one to three methyne groups may be replaced by nitrogen atoms and in the heterocyclyl moiety a methylene group may be replaced by a carbonyl group and a sulphur atom may be replaced by a sulphinyl or sulphonyl group, a 5-oxo-4,5-dihydro-benzo[f][1,3,4]oxadiazepinyl group wherein in the benzo moiety one to three methyne groups may be replaced by nitrogen atoms, an 11H-dibenzo[b,e]azepinyl or 5H-dibenzo[a,d]cycloheptenyl group, wherein in each case in the benzo moiety one to three methyne groups may be replaced by nitrogen atoms and the methylene group in the heterocyclyl moiety may be replaced by an oxygen or sulphur atom, a carbonyl, sulphinyl, sulphonyl or an imino group substituted by R x, where R x denotes a hydrogen atom or a C1-4-alkyl, C2-4-alkenyl, C2-4-alkynyl, C3-6-cycloalkyl, C3-6-cycloalkyl-C1-3-alkyl, aryl, aryl-C1-3-alkyl, hydroxy-C2-4-alkyl, C1-3-alkyloxy-C2-4-alkyl, C3-6-cycloalkyloxy-C2-4-alkyl, amino-C2-4-alkyl, C1-3-alkylamino-C2-4-alkyl, di-(C1-3-alkyl)-amino-C2-4-alkyl, C1-3-alkyl-carbonyl, C1-3-alkyloxy-carbonyl, C1-3-alkyloxy-carbonyl-C1-3-alkyl, aryl-carbonyl, C1-3-alkyl-sulphonyl or aryl-sulphonyl group, a phenanthridinyl, 1,2,3,4-tetrahydro-phenanthridinyl, benzo[f]quino-xalinyl, 5H-dibenzo[d,f][1,3]diazepinyl, 5H-benzo[e]pyrrolo[1,2-a][1,4]diazepinyl, thieno[3,2-b][1,4]benzoxazepinyl or a 3-oxo-2,3-dihydro-isoindol-1-ylidene group, wherein in each case in the benzo moiety one to three methyne groups may be replaced by nitrogen atoms, a benzo[1,2,5]oxadiazolyl, dibenzofuranyl, Indolizinyl, 1H-perimidinyl, group, a pyrazolo[1,5-c]quinazolinyl group or an imidazo[2,1-a]isoquinolinyl or imidazo[1,2-a]isoquinolinyl group while the above-mentioned groups R a may be substituted by the groups R10 to R13 and may additionally be substituted by a C1-3-alkyl group 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, cyano-C1-3-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, or 4-(C1-3-alkyl)-piperazin-1-yl group, a C1-3-alkyl-carbonylamino, arylcarbonylamino, aryl-C1-3-alkyl-carbonylamino, C1-3-alkyloxy-carbonylamino, aminocarbonylamino, C1-3-alkyl-aminocarbonylamino, di-(C1-3-alkyl)aminocarbonylamino, pyrrolidin-1-yl-carbonylamino, piperidin-1-yl-carbonylamino, morpholin-4-yl-carbonylamino, piperazin-1-yl-carbonylamino or 4-(C1-3-alkyl)-piperazin-1-yl-carbonylamino, C1-3-alkyl-sulphonylamino, bis-(C1-3-alkylsulphonyl)-amino, aminosulphonylamino, C1-3-alkylamino-sulphonylamino, di-(C1-3-alkyl)amino-sulphonylamino, pyrrolidin-1-yl-sulphonylamino, piperidin-1-yl-sulphonylamino, morpholin-4-yl-sulphonylamino, piperazin-1-yl-sulphonylamino or 4-(C1-3-alkyl)-piperazin-1-yl-sulphonylamino, (C1-3-alkylamino)thiocarbonylamino, (C1-3-alkyloxy-carbonylamino)-carbonylamino, 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-C1-3-alkyl-carbonylamino, N-(C1-3-alkyl)-C1-3-alkyloxy-carbonylamino, N-(aminocarbonyl)-C1-3-alkylamino, N-(C1-3-alkyl-aminocarbonyl)-C1-3-alkylamino, N-[di-(C1-3-alkyl)aminocarbonyl]-C1-3-alkylamino, N-(C1-3-alkyl)-C1-3-alkyl-sulphonylamino, N-(C1-3-alkyl)-arylsulphonylamino or N-(C1-3-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 may be substituted in each case by a methyl or ethyl 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-1-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-alkyl)-piperazin-1-yl-carbonyl-C1-3-alkyl group, a carboxy-C1-3-alkyloxy, C1-3-alkyloxy-carbonyl-C1-3-alkyloxy, cyano-C1-3-alkyloxy, aminocarbonyl-C1-3-alkyloxy, C1-3-alkyl-aminocarbonyl-C1-3-alkyloxy, di-(C1-3-alkyl)-aminocarbonyl-C1-3-alkyloxy, pyrrolidin-1-yl-carbonyl-C1-3-alkyloxy, piperidin-1-yl-carbonyl-C1-3-alkyloxy, morpholin-4-yl-carbonyl-C1-3-alkyl-oxy, piperazin-1-yl-carbonyl-C1-3-alkyloxy or 4-(C1-3-alkyl)-piperazin-1-yl-carbonyl-C1-3-alkyloxy group, a hydroxy-C1-3-alkyl, C1-3-alkyloxy-C1-3-alkyl, amino-C1-3-alkyl, C1-3-alkylamino-C1-3-alkyl, di-(C1-3-alkyl)-amino-C1-3-alkyl, pyrrolidin-1-yl-C1-3-alkyl, piperidin-1-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, C1-3-alkyl-sulphanyl-C1-3-alkyloxy, C1-3-alkylsulphinyl-C1-3-alkyloxy, C1-3-alkylsulphonyl-C1-3-alkyloxy, amino-C1-3-alkyloxy, C1-3-alkylamino-C1-3-alkyloxy, di-(C1-3-alkyl)-amino-C1-3-alkyloxy, pyrrolidin-1-yl-C1-3-alkyloxy, piperidin-1-yl-C1-3-alkyloxy, morpholin-4-yl-C1-3-alkyloxy, piperazin-1-yl-C1-3-alkyloxy, 4-(C1-3-alkyl)-piperazin-1-yl-C1-3-alkyloxy group, a mercapto, C1-3-alkylsulphanyl, C1-3-alkylsulphinyl, C1-3-alkylsulphonyl, C1-3-alkylsulphonyloxy, arylsulphonyloxy, trifluoromethylsulphanyl, trifluoromethylsulphinyl or trifluoromethylsulphonyl group, a sulpho, aminosulphonyl, C1-3-alkyl-aminosulphonyl, di-(C1-3-alkyl)-aminosulphonyl, pyrrolidin-1-yl-sulphonyl, piperidin-1-yl-sulphonyl, 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 C3-4-alkenyloxy or C3-4-alkynyloxy 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, R11 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, ethylenedioxy or a straight-chain C3-5-alkylene group and R13 denotes a hydrogen atom, a fluorine, chlorine or bromine atom, a trifluoromethyl, C1-3-alkyl or C1-3-alkyloxy group, R2 denotes a hydrogen atom, a C1-6-alkyl group, a C2-4-alkenyl group, a C3-4-alkynyl group, a C3-4-cycloalkyl group, a C3-4-cycloalkyl-C1-3-alkyl group, a tetrahydrofuran-3-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, tetrahydrofuranylmethyl or tetrahydropyranylmethyl group, an aryl group, an aryl-C1-4-alkyl group, an aryl-C2-3-alkenyl group, an arylcarbonyl-C1-2-alkyl group, a heteroaryl-C1-3-alkyl group, 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, an aryl-A-C1-3-alkyl group, while A denotes an oxygen or sulphur atom, an imino, C1-3-alkylimino, sulphinyl or sulphonyl group, a C1-4-alkyl group substituted by a group R b, while R b denotes a cyano, carboxy, C1-3-alkyloxy-carbonyl, aminocarbonyl, C1-3-alkylamino-carbonyl, di-(C1-3-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, or a C2-4-alkyl group substituted by a group R c, while R c 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 3 position of the xanthine structure by at least two carbon atoms, R3 denotes a C3-8-alkyl group, a C1-3-alkyl group substituted by a group R d, while R d 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, while the above-mentioned heterocyclic groups may be substituted in each case 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 amino, C1-3-alkylamino or a di-(C1-3-alkyl)amino group and may additionally be substituted by one or two C1-3-alkyl groups, a piperidin-1-yl or hexahydroazepin-1-yl group which is substituted in the 3 position or in the 4 position by an amino, C1-3-alkylamino or a di-(C1-3-alkyl)amino group and may additionally be substituted by one or two C1-3-alkyl groups, 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 in 2 position or in 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, while this bridge contains 2 to 5 carbon atoms, if the two hydrogen atoms are located on the same carbon atom, or contains 1 to 4 carbon atoms if the hydrogen atoms are located on adjacent carbon atoms, or contains 1 to 4 carbon atoms, if the hydrogen atoms are located on carbon atoms which by are separated by one atom, or contains 1 to 3 carbon atoms if the two hydrogen atoms are located on carbon atoms which are 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 by an amino group in the 6 position, 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-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, while the two nitrogen atoms on the cycloalkyl moiety are separated from one another by at least two carbon atoms, an 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, while the two nitrogen atoms on 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-alkyl)amino-C1-3-alkyl group, an 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-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, 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-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 R19-C2-4-alkylamino group wherein R19 is separated from the nitrogen atom of the C2-4-alkylamino moiety by at least two carbon atoms and R19 denotes an amino, C1-3-alkylamino or di-(C1-3-alkyl)-amino group, an R19-C2-4-alkylamino group wherein the nitrogen atom of the C2-4-alkylamino moiety is substituted by a C1-3-alkyl group and R19 is separated from the nitrogen atom of the C2-4-alkylamino moiety by at least two carbon atoms, while R19 is as hereinbefore defined, 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, while the groups mentioned for R20 may each be substituted by one or two C1-3-alkyl groups, an amino group substituted by the group R20 and a C1-3-alkyl group wherein R20 is as hereinbefore defined, while 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-chain and may additionally be substituted by one or two C1-3-alkyl groups, while R19 is as hereinbefore defined, 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, while the above-mentioned groups may each be substituted by one or two C1-3-alkyl groups, while by the aryl groups mentioned in the definition of the above groups are meant phenyl or naphthyl groups, which may be mono- or disubstituted by R h independently of one another, where the substituents are identical or different and R h 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 definitions of the above mentioned 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, and the above-mentioned heteroaryl groups may be mono- or disubstituted by R h, while the substituents may be identical or different and R h is as hereinbefore defined, and, unless otherwise specified, the above-mentioned alkyl, alkenyl and alkynyl groups may be straight-chain or branched, the tautomers, enantiomers, diastereomers, the mixtures thereof, the prodrugs thereof and the salts thereof.
2. Compounds of general formula I according to claim 1, wherein R1 denotes a methyl group substituted by a group R a, where R a denotes a 1,4-dihydro-quinazolinyl or 3,4-dihydro-quinazolinyl group, a 3,4-dihydro-isoquinolinyl group, a 1H-benzo[d][1,2]oxazinyl or 1-oxo-1H-benzo[d][1,2]oxazinyl group, a 4H-benzo[e][1,3]oxazinyl or 4-oxo-4H-benzo[e][1,3]oxazinyl group, a 4H-benzo[d][1,3]oxazinyl or 4-oxo-4H-benzo[d][1,3]oxazinyl group, 2H-benzo[1,4]oxazinyl or 2-oxo-2H-benzo[1,4]oxazinyl group, a 4H-benzo[e][1,3]thiazinyl or 4-oxo-4H-benzo[e][1,3]thiazinyl group, a 4H-benzo[d][1,3]thiazinyl or 2H-benzo[1,4]thiazinyl group, a 2-oxo-2H-benzo[e][1,3]oxazinyl or 2,2-dioxo-1H-benzo[c][1,2]thiazinyl group, a 2,3-dihydro-1H-benzo[e][1,4]diazepinyl or 2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepinyl group, a 4,5-dihydro-3H-benzo[b][1,4]diazepinyl or 4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepinyl group, a 5-oxo-4,5-dihydro-3H-benzo[e][1,4]diazepinyl group, a 2,3-dihydro-benzo[f][1,4]oxazepinyl or 2,3-dihydro-benzo[b][1,4]oxazepinyl group, a 2,3-dihydro-benzo[t][1,4]thiazepinyl- 2,3-dihydro-benzo[b][1,4]thiazepinyl group, a 5-oxo-4,5-dihydro-benzo[f][1,3,4]oxadiazepinyl group, an 11H-dibenzo[b,e]azepinyl or 11-oxo-11H-dibenzo[b,e]azepinyl group, an 11 H-benzo[e]pyrido[3,2-b]azepinyl group, a 5H-dibenzo[b,e][1,4]diazepinyl or dibenzo[b,f][1,4]oxazepinyl group, a dibenzo[b,f][1,4]thiazepinyl, 5-oxo-dibenzo[b,f][1,4]thiazepinyl or 5,5-dioxo-dibenzo[b,f][1,4]thiazepinyl group, 5H-dibenzo[a,d]cycloheptenyl or 5H-dibenzo[b,f]azepinyl group, a phenanthridinyl, benzo[c][1,5]naphthyridinyl, benzo[h][1,6]naphthyri-dinyl, benzo[c][1,8]naphthyridinyl or 1,2,3,4-tetrahydro-phenanthridinyl group, a benzo[f]quinoxalinyl group, a 5H-dibenzo[d,f][1,3]diazepinyl, 5H-benzo[e]pyrrolo[1,2-.alpha.][1,4]diazepinyl or thieno[3,2-b][1,4]benzoxazepinyl group, a 3-oxo-2,3-dihydro-isoindol-1-ylidene group, a benzo[1,2,5]oxadiazolyl group, a dibenzofuranyl group, an indolizinyl group, a 1 H-perimidinyl group, a pyrazolo[1,5-c]quinazolinyl group or an imidazo[2,1-a]isoquinolinyl or imidazo[1,2-a]isoquinolinyl group while the benzo groups of the above-mentioned groups R a are substituted by the groups R10 to R12 and the alkylene units of the above-mentioned groups R a may be substituted by one or two C1-3-alkyl or C1-3-alkyloxy-carbonyl groups, while the groups may be identical or different, or by a trifluoromethyl group, and the imino groups of the above-mentioned groups R a may be substituted by a C1-3-alkyl group and R10 denotes a hydrogen atom, a fluorine, chlorine, bromine or iodine atom, a C1-3-alkyl or cyclopropyl group, a hydroxy, C1-3-alkyloxy or cyclopropyloxy group, a nitro, amino, C1-3-alkylamino or di-(C1-3-alkyl)amino group, a C1-3-alkyl-carbonylamino or C1-3-alkyl-sulphonylamino group, a cyano, carboxy, C1-3-alkyloxy-carbonyl, aminocarbonyl, C1-3-alkyl-aminocarbonyl or di-(C1-3-alkyl)-aminocarbonyl group, a mercapto, C1-3-alkylsulphanyl, C1-3-alkylsulphinyl or C1-3-alkylsulphonyl or aminosulphonyl group or a difluoromethyl, trifluoromethyl, difluoromethoxy or trifluoromethoxy group and R11 and R12, which may be identical or different, in each case represent a hydrogen atom, a fluorine, chlorine or bromine atom, a methyl, trifluoromethyl or methoxy group, R2 denotes a hydrogen atom, a C1-3-alkyl group, a C3-6-cycloalkyl group or a phenyl group optionally mono- or disubstituted by 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, while the substituents may be identical or different, R3 denotes a 2-buten-1-yl or 3-methyl-2-buten-1-yl group, a 2-butyn-1-yl group or a 1-cyclopenten-1-ylmethyl group and R4 denotes a (3-amino-piperidin-1-yl) group, while, unless otherwise stated, the above-mentioned alkyl groups may be straight-chain or branched, the tautomers, enantiomers, diastereomers, the mixtures thereof and the salts thereof.
3. Compounds of general formula I according to claim 2, wherein R1 denotes a methyl group substituted by a group R a, where R a denotes a 1,4-dihydro-quinazolin-2-yl or 3,4-dihydro-quinazolin-2-yl group, a 3,4-dihydro-isoquinolin-1-yl group, a 1H-benzo[d][1,2]oxazin-4-yl or 1-oxo-1H-benzo[d][1,2]oxazin-4-yl group, a 4H-benzo[e][1,3]oxazin-2-yl or 4-oxo-4H-benzo[e][1,3]oxazin-2-yl group, a 4H-benzo[d] [1,3]oxazin-2-yl or 4-oxo-4H-benzo[d][1,3]oxazin-2-yl group, 2H-benzo[1,4]oxazin-3-yl or 2-oxo-2H-benzo[1,4]oxazin-3-yl group, a 4H-benzo[e][1,3]thiazin-2-yl or 4-oxo-4H-benzo[e][1,3]thiazin-2-yl group, a 4H-benzo[d][1,3]thiazin-2-yl or 2H-benzo[1,4]thiazin-3-yl group, a 2-oxo-2H-benzo[e][1,3]oxazin-4-yl or 2,2-dioxo-1H-benzo[c][1,2]thia-zin-4-yl group, a 2,3-dihydro-1H-benzo[e][1,4]diazepin-5-yl or 2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-5-yl group, a 4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl or 4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl group, a 5-oxo-4,5-dihydro-3H-benzo[e][1,4]diazepin-2-yl group, a 2,3-dihydro-benzo[f][1,4]oxazepin-5-yl or 2,3-dihydro-benzo[b]-[1,4]oxazepin-4-yl group, a 2,3-dihydro-benzo[f][1,4]thiazepin-5-yl or 2,3-dihydro-benzo[b]-[1,4]thiazepin-4-yl group, a 5-oxo-4,5-dihydro-benzo[f][1,3,4]oxadiazepin-2-yl group, an 11H-dibenzo[b,e]azepin-6-yl or 11-oxo-11H-dibenzo[b,e]azepin-6-yl group, an 11 H-benzo[e]pyrido[3,2-b]azepin-6-yl group a 5H-dibenzo[b,e][1,4]diazepin-11-yl or dibenzo[b,f][1,4]oxazepin-11-yl group, a dibenzo[b,f][1,4]thiazepin-11-yl, 5-oxo-dibenzo[b,f][1,4]thiazepin-11-yl or 5,5-dioxo-dibenzo[b,f][1,4]thiazepin-11-yl group, a 5H-dibenzo[a,d]cyclohepten-10-yl or 5H-dibenzo[b,f]azepin-10-yl group, a phenanthridin-6-yl, benzo[c][1,5]naphthyridin-6-yl, benzo[h][1,6]naph-thyridin-5-yl, benzo[c][1,8]naphthyridin-6-yl or 1,2,3,4-tetrahydro-phenanthridin-6-yl group, a benzo[f]quinoxalin-6-yl group, a 5H-dibenzo[d,f][1,3]diazepin-6-yl, 5H-benzo[e]pyrrolo[1,2-.alpha.][1,4]diazepin-11-yl or thieno[3,2-b][1,4]benzoxazepinyl-9-yl group, a 3-oxo-2,3-dihydro-isoindol-1-ylidene group, a benzo[1,2,5]oxadiazol-5-yl group, a dibenzofuran-2-yl group, an indolizin-2-yl group, a 1H-perimidin-2-yl group, a pyrazolo[1,5-c]quinazolin-5-yl group or an imidazo[2,1-a]isoquinolin-2-yl or imidazo[1,2-a]isoquinolin-2-yl group while the benzo groups of the above-mentioned groups R a are substituted by the groups R10 to R12 and the alkylene units of the above-mentioned groups R a may be substituted by one or two methyl-or methoxy-carbonyl groups, while the groups may be identical or different, or by a trifluoromethyl group and the imino groups of the above-mentioned groups R a may be substituted by a methyl group and R10 denotes a hydrogen atom, a fluorine, chlorine, bromine or iodine atom, a methyl or ethyl group, a hydroxy, methoxy or ethoxy group or a difluoromethyl, trifluoromethyl, difluoromethoxy or trifluoromethoxy group and R11 and R12, which may be identical or different, each represent a hydrogen atom, a fluorine, chlorine or bromine atom, a methyl, trifluoromethyl or methoxy group, R2 denotes a hydrogen atom or a methyl, ethyl, propyl, isopropyl, phenyl or cyclopropyl group, R3 denotes a 2-buten-1-yl or 3-methyl-2-buten-1-yl group, a 2-butyn-1-yl group or a 1-cyclopenten-1-ylmethyl group and R4 denotes a (3-amino-piperidin-1-yl) group, the tautomers, enantiomers, diastereomers, the mixtures thereof and the salts thereof.
4. Compounds of general formula I according to claim 3, wherein R1 denotes a 3-methoxycarbonyl-3-methyl-3,4-dihydro-isoquinolin-1-ylmethyl group, a 1-methyl-2,2-dioxo-1H-benzo[c][1,2]thiazin-4-ylmethyl group, a 2,3-dihydro-benzo[f][1,4]oxazepin-5-ylmethyl group, a 2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-5-ylmethyl group, a phenanthridin-6-ylmethyl or 1,2,3,4-tetrahydro-phenanthridin-6-ylmethyl group, an 11H-dibenzo[b,e]azepin-6-ylmethyl group, a dibenzo[b,f][1,4]oxazepin-11-ylmethyl group, a 3-oxo-2,3-dihydro-isoindol-1-ylidenemethyl group, a 3-trifluoromethyl-3,4-dihydro-isoquinolin-1-ylmethyl group, a 3,4-dihydro-quinazolin-2-ylmethyl group, a 5-methyl-5H-dibenzo[b,e][1,4]diazepin-11-ylmethyl group, an 8-methyl-dibenzo[b,f][1,4]oxazepin-11-ylmethyl group, a benzo[1,2,5]oxadiazol-5-ylmethyl group, an 8-methyl-phenanthridin-6-ylmethyl group, a 1-methyl-phenanthridin-6-ylmethyl group, a 4-methyl-phenanthridin-6-ylmethyl group, a benzo[h][1,6]naphthyridin-5-ylmethyl group, a pyrazolo[1,5-c]quinazolin-5-yl group, a benzo[c][1,8]naphthyridin-6-ylmethyl group, a benzo[c][1,5]naphthyridin-6-ylmethyl group, a 1H-perimidin-2-ylmethyl group, a benzo[f]quinoxalin-6-ylmethyl group or an imidazo[2,1-a]isoquinolin-2-ylmethyl or imidazo[1,2-a]isoquinolin-2-ylmethyl group, R2 denotes a methyl or cyclopropyl group, R3 denotes a 2-buten-1-yl, 3-methyl-2-buten-1-yl or 2-butyn-1-yl group and R4 denotes a (3-amino-piperidin-1-yl) group, the tautomers, enantiomers, diastereomers, the mixtures thereof and the salts thereof.
5. The following compounds of general formula I according to claim 1:
(1) 1-[(1-methyl-2,2-dioxo-1H-benzo[c][1,2]thiazin-4-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine¦, (2) 1-[(3-methoxycarbonyl-3-methyl-3,4-dihydro-isoquinolin-1-yl]methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine¦, (3) 1-[(2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-5-yl)methyl]-3-methyl-7-((E)-2-buten-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine, (4) 1-[(phenanthridin-6-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine¦, (5) 1-[(1,2,3,4-tetrahydro-phenanthridin-6-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine¦, (6) 1-[(11H-dibenzo[b,e]azepin-6-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine¦, (7) 1-[(dibenzo[b,f][1,4]oxazepin-11-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine¦, (8) 1-[(3-trifluoromethyl-3,4-dihydro-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine¦, (9) 1-[(dibenzo[b,f][1,4]oxazepin-11-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine¦, (10) 1-[(3,4-dihydro-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine¦, (11) 1-[(5-methyl-5H-dibenzo[b,e](1,4]diazepin-11-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine¦, (12) 1-[(8-methyl-dibenzo[b,f][1,4]oxazepin-11-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine¦, (13) 1-[(benzo[1,2,5]oxadiazol-5-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine¦, (14) 1-[(phenanthridin-6-yl)methyl]-3-cyclopropyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine¦, (15) 1-[(8-methyl-phenanthridin-6-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine¦, (16) 1-[(phenanthridin-6-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine¦, (17) 1-[(phenanthridin-6-yl)methyl]-3-cyclopropyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine¦, (18) 1-[(1-methyl-phenanthridin-6-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine¦, (19) 1-[(4-methyl-phenanthridin-6-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine¦, (20) 1-[(benzo[h][1,6]naphthyridin-5-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine¦, (21) 1-[(pyrazolo[1,5-c]quinazolin-5-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine¦, (22) 1-[(benzo[c][1,8]naphthyridin-6-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine¦, (23) 1-[(benzo[c][1,5]naphthyridin-6-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine¦, (24) 1-[(1H-perimidin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine¦, (25) 1-[(benzo[f]quinoxalin-6-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine¦, (26) 1-[(imidazo[2,1-a]isoquinolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine¦, (27) 1-[(imidazo[1,2-a]isoquinolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine¦, (28) 1-[(phenanthridin-6-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine¦, (29) 1-[(2,3-dihydro-benzo(t][1,4]oxazepin-5-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine¦, and (30) 1-[(3-oxo-2,3-dihydro-isoindol-1-ylidene)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine¦
and the salts thereof.
6. Physiologically acceptable salts of the compounds according to at least one of claims 1 to 5 with inorganic or organic acids or bases.
7. Pharmaceutical compositions containing a compound according to at least one of claims 1 to 5 or a physiologically acceptable salt according to claim 6 optionally together with one or more inert carriers and/or diluents.
8. Use of a compound according to at least one of claims 1 to 6 for preparing a pharmaceutical composition which is suitable for the treatment of type I and type II diabetes mellitus, arthritis, obesity, allograft transplantation and osteoporosis caused by calcitonin.
9. Process for preparing a pharmaceutical composition according to claim 7, characterised in that a compound according to at least one of claims 1 to 6 is incorporated in one or more inert carriers and/or diluents by a non-chemical method.
10. Process for preparing the compounds of general formula I according to claims 1 to 6, characterised in that a) a compound of general formula wherein R1, R2 and R3 are defined as mentioned in claim 1 and R4' ' denotes one of the groups mentioned for R4 hereinbefore which contain an imino, amino or alkylamino group, while the imino, amino or alkylamino group is substituted by a protective group, is deprotected, b) a compound of general formula wherein R2 and R3 are defined as mentioned in claim 1, R4' ' denotes one of the groups mentioned for R4 hereinbefore which contain an imino, amino or alkylamino group, while the imino, amino or alkylamino group is substituted by one of the protective groups mentioned above, X denotes an oxygen or sulphur atom, a sulphinyl, sulphonyl or an imino group substituted by R x, and the -CH2-CH2-X-phenyl unit is substituted by R10 to R14 and may additionally be substituted by a C1-3-alkyl group, while R x and R10 to R14 are as hereinbefore defined, and PG also denotes one of the protective groups mentioned above, while the two protective groups may be cleaved simultaneously or one after the other, is deprotected and cyclised, c) in order to prepare a compound of general formula I wherein R1 denotes a 3-oxo-2,3-dihydro-isoindol-1-ylidenemethyl group optionally substituted by a group as defined in claims 1 to 5, a compound of general formula wherein the benzo group is substituted by R10 to R14, and R10 to R14 as well as R x, R2 and R3 are as hereinbefore defined, and R4~' denotes one of the groups mentioned for R4 hereinbefore which contain an imino, amino or alkylamino group, while the imino, amino or alkylamino group is substituted by one of the protective groups mentioned above, and the dehydration is carried out under the same reaction conditions as the cleaving of the protective group, is deprotected and dehydrated, the compounds of general formula I thus obtained are resolved into their enantiomers and/or diastereomers and/or the compounds of formula I obtained are converted into their salts, particularly for pharmaceutical use into the physiologically acceptable salts thereof with inorganic or organic acids or bases.
CA2505389A 2002-11-08 2003-11-03 Xanthine derivatives, the preparation thereof and their use as pharmaceutical compositions Expired - Fee Related CA2505389C (en)

Applications Claiming Priority (3)

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DE10251927.7 2002-11-08
DE10251927A DE10251927A1 (en) 2002-11-08 2002-11-08 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
PCT/EP2003/012198 WO2004041820A1 (en) 2002-11-08 2003-11-03 Novel xanthine derivatives, the production and the use thereof in the form of drugs

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