8- (3-Aminopiperidin-1-yl) -7-but-2-inyl-3-methyl-1- (4-methylchinazolin-2-ylmethyl) -3,7-dihydropurin-2,6-dion, the enantiomers and their salts, in particular Linagliptin * combined with metformin hydrochloride. * Linagliptin = ((R) -8- (3-Aminopiperidin-1-yl) -7-but-2-inyl-3-methyl-1 (4-methylchinazolin-2-ylmethyl) -3,7-dihydropurin-2,6-dion) (IUPAC)

摘要

8-(3-amino-piperidin-1-yl)-xanthine derivatives (I) are new. 8-(3-amino-piperidin-1-yl)-xanthine derivatives of formula (I) and their tautomers, enantiomers, diastereomers (or mixtures), prodrugs and salts are new. [Image] R 1 : CH 2Q 1, CH 2CH 2OMe, CH 2CH 2OPh, CH 2CH 2CN, CH 2COPh or CHMeCOPh, phenylcarbonylmethyl mono-substituted in the ring by Q 2 or phenylcarbonylmethyl substituted in the ring by two OMe groups or on two adjacent C-atoms by OCH 2O, OCH 2CH 2O or N(Me)COO; Q 1 : CONMe 2, heterocycle or heteroaryl (optionally substituted); Q 2 : NH 2, NHCH 2CN, NHCOMe, NHCOEt, NHCOCHMe 2, NHCOOMe, NHCONHCOOEt, 2-oxo-imidazolin-1-yl, COOH, COMe, COOEt, CONH 2, CONHMe, CONMe 2, morpholinocarbonyl, SMe, SOMe, SO 2Me, OCH 2COOH, OCH 2COOEt, OCH 2COOCHMe 2, OCH 2CONH 2, OCH 2CONHMe, OCH 2CONHEt, OCH 2CONHCHMe 2, OCH 2CONMe 2, pyrrolidinocarbonyl-methoxy, morpholinocarbonyl-methoxy, OCHMeCOOEt, OCHMeCONH 2 or OCH 2SOMe; R 2 : Me, CHMe 2 or Ph, and R 3 : CH 2C(Me)=CH 2, CH 2C(Cl)=CH 2, CH 2CH=CHBr, CH 2CH=CHMe, CH 2C(Me)=CMe 2, CH 2CCMe, 1-cyclopenten-1-ylmethyl or 2-furanylmethyl. An independent claim is included for the preparation of (I). ACTIVITY : Antidiabetic; Antiarthritic; Anorectic; Immunosuppressive; Osteopathic; Ophthalmological; Nephrotropic; Neuroprotective; Antiarteriosclerosis; Tranquilizer; Cardiant; Diuretic; Hypotensive; Antiinflammatory; Antiulcer; Antiinfertility; Antirheumatic; Antithyroid; Virucide; Anti-HIV; Cytostatic; Nootropic; Cerebroprotective; Antiparkinsonian; Antimigraine; Antianemic; Dermatological; Antipsoriatic; Antidepressant. MECHANISM OF ACTION : Dipeptidylpeptidase-IV (DPP-IV) inhibitor; B-cell degeneration inhibitor; glucagon-like peptide (GLP) action modulator. 1-((Quinazolin-2-yl)-methyl)-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine (Ia) had an IC 50 value of 1 nM for inhibition of DPP-IV.