Patent DE-102004012921-A1 (DE)
Title: New 7-butynyl-8-(3-amino-1-piperidinyl)xanthine derivatives useful as dipeptidyl peptidase IV inhibitors, e.g. for treating diabetes, arthritis, obesity and osteoporosis
Inventor: HIMMELSBACH FRANK
IPC: A61K31/522
Filed: 2004-03-17
Abstract: 7-Butynyl-8-(3-amino-1-piperidinyl)xanthine derivatives (I) are new. 7-Butynyl-8-(3-amino-1-piperidinyl)xanthine derivatives of formula (I) and their tautomers, isomers and salts are new. R : benzyl, 2-fluorobenzyl, 3-fluorobenzyl, 4-fluorobenzyl, 2,6-difluoro-benzyl, 3,4-difluoro-benzyl, 2-chlorobenzyl, 3-chlorobenzyl or 4-chlorobenzyl, 2-trifluoromethyl-benzyl, 3-trifluoromethyl-benzyl or 4-trifluoromethyl-benzyl, 3-trifluoromethoxy-benzyl or 4-trifluoromethoxy-benzyl, 2-cyanobenzyl, 3-cyanobenzyl or 4-cyanobenzyl, 2,6-dicyanobenzyl, 3,4-dicyanobenzyl, 3,5-dicyanobenzyl, 2-trifluoromethyl-4-cyano-benzyl, 3-nitro-4-cyano-benzyl, 2-cyano-3-methoxy-benzyl, 2-cyano-4-methoxy-benzyl, 2-cyano-5-methoxy-benzyl, 2-cyano-4-fluoro-benzyl, 2-cyano-5-fluoro-benzyl, 2-cyano-6-fluoro-benzyl, 3-cyano-4-fluoro-benzyl, 4-cyano-3-fluorobenzyl, 2-fluoro-4-cyano-benzyl, 2-cyano-3-chlorobenzyl, 2-chloro-4-cyano-benzyl or 2-cyano-4-bromobenzyl, 2-methoxy-benzyl, 3-methoxy-benzyl, 4-methoxy-benzyl, 2-fluoro-3-methoxybenzyl, 2-fluoro-4-methoxy-benzyl, 2-fluoro-5-methoxy-benzyl, 3-fluoro-4-methoxybenzyl, 3,4-dimethoxy-benzyl, 3,5-dimethoxybenzyl or 3,4-dimethoxy-6-fluorobenzyl, (benzo[1,3]dioxol-5-yl)methyl, [(4-cyano-benzo[1,3]dioxol-5-yl)methyl, 2-(3-cyclopropyloxy-phenyl)-2-oxo-ethyl, 2-(3-cyclopropylmethoxy-phenyl)-2oxo-ethyl or 2-(3-cyclobutyloxy-phenyl)-2-oxo-ethyl, 2-oxo-2-[2-(pyridin-3-yl)-phenyl]-ethyl or 2-oxo-2-[2-(pyridin-4-yl)-phenyl]ethyl, (3-cyano-1-naphthyl)methyl, (1,4-dicyano-2-naphthyl)methyl or (2,4-dimethoxy-1-naphthyl)methyl, (furan-2-yl)methyl, (furan-3-yl)methyl, (5-bromo-furan-2-yl)methyl, (5-methylfuran-2-yl)methyl, (5-cyano-furan-2-yl)methyl or (5-methoxycarbonyl-furan-2yl)methyl, (pyridin-2-yl)methyl, (6-fluoro-pyridin-2-yl)methyl or (5-methoxy-pyridin-2-yl)methyl, (3-cyanopyridin-2-yl)methyl, (6-cyanopyridin-2- yl)methyl, (5-cyano-pyridin-2-yl)methyl, (4-cyano-pyridin-2-yl)methyl, (4-cyano-pyridin-3-yl)methyl, (3-cyanopyridin-4-yl)methyl, (2-cyano-pyridin-3-yl)methyl, (2-cyano-pyridin-4-yl)methyl, (5cyano-pyridin-3-yl)methyl, (6-cyano-pyridin-3-yl)methyl or (5-cyano-6-methoxypyridin-2-yl)methyl, (6-phenyl-pyridin-2-yl)methyl or ([2,2']bipyridinyl-6-yl)methyl, (pyrimidin-2-yl)methyl, (4-methyl-pyrimidin-2-yl)methyl or (4,6-dimethylpyrimidin-2-yl)methyl, (2-phenyl-pyrimidin-4-yl)methyl or (4-phenyl-pyrimidin-2-yl)methyl, [(1-methyl-1H-benzotriazol-5-yl)methyl], (6-fluoro-quinolin-2-yl)methyl, (7-fluoro-quinolin-2-yl)methyl, (2-methyl-quinolin-4-yl)methyl, (3-cyano-quinolin-2-yl)methyl, (3-cyano-4-methyl-quinolin-2-yl)methyl, (4-cyano-quinolin-2-yl)methyl, (5-cyano-quinolin-2-yl)methyl, (6-cyano-quinolin-2-yl)methyl, (6-amino-quinolin-2-yl)methyl, (8-amino-quinolin-2-y1)methyl, (4-methoxy-quinolin-2-yl)methyl, (6-methoxy-quinolin-2-yl)methyl, (6,7-dimethoxyquinolin-2-yl)methyl or (8-cyano-quinolin-7-yl)methyl, (1-cyano-isoquinolin-3-yl)methyl, (4-cyano-isoquinolin-1-yl)methyl, (4-cyanoisoquinolin-3-yl)methyl or [(4-(pyridin-2-yl)-isoquinolin-1-yl)methyl, (quinazolin-6-yl)methyl, (quinazolin-7-yl)methyl, (2-methyl-quinazolin-4yl)methyl, (4,5-dimethyl-quinazolin-2-yl)methyl, (4-ethyl-quinazolin-2-yl)methyl, (4-cyclopropyl-quinazolin-2-yl)methyl, (2-phenyl-quinazolin-4-yl)methyl, (4-cyanoquinazolin-2-yl)methyl, (4-phenylamino-quinazolin-2-yl)methyl or (4-benzylaminoquinazolin-2-yl)methyl, (quinoxalin-5-yl)methyl, (quinoxalin-6-yl)methyl or (2,3-dimethyl-quinoxalin-6-yl)methyl, or ([1,5]naphthyridin-3-yl)methyl. An independent claim is also included for a process for preparing (I). [Image] ACTIVITY : Antidiabetic; Antiarthritic; Anorectic; Osteopathic; Tranquilizer; Hypotensive; Nephrotropic; Antiinflammatory; Antiulcer; Immunosuppressive; Virucide; Anti-HIV; Neuroprotective; Nootropic; Cytostatic; Cerebroprotective; Vasotropic; Antiparkinsonian; Antimigraine; Dermatological; Antipsoriatic; Antidepressant; Neuroleptic. MECHANISM OF ACTION : Dipeptidyl peptidase IV (DPP IV) inhibitor. 1-(4-Benzylamino-4-quinazolinylmethyl)-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-1-piperidinyl)xanthine had an IC50 of 6 nM against DPP IV activity in Caco-2 cell extracts.