Xanthin derivatives, their production and utilisation as medicine

摘要

8-substituted-xanthine derivatives (I), their tautomers, enantiomers, diastereomers or mixtures, and salts. 8-substituted xanthine derivatives of formula (I), their tautomers, enantiomers, diastereomers or mixtures, and salts, are new: [Image] R 1>hydrogen; 1-8C alkyl; 3-8C alkenyl or alkynyl; 3-4C alkenyl substituted by 1-2C alkoxycarbonyl, aminocarbonyl (optionally substituted by 1 or 2 1-3C alkyl) or het-CO; 1-6C alkyl substituted by Ra; phenyl(1-6C)alkyl, optionally ring-substituted by R 1> 0>-R 1> 4>; phenyl(1-4C)alkyl, optionally substituted in alkyl by Rz and in the ring by R 1> 0>-R 1> 4>; R 1> 0>-R 1> 4>-substituted phenyl; phenyl(2-3C) alkenyl, phenyl (or naphthyl)-(CH 2) m-(A or B)-(CH 2) n, naphthyl(1-3C)alkyl or phenylcarbonylmethyl (all optionally ring-substituted by R 1> 0>-R 1> 4>); [1,4-napththoquinon-2-yl; chromen-4-on-3-yl; 1-oxo- or 1,3-dioxo-indan-2-yl; 2,3-dihydro-3-oxo-benzofuran-2-yl; heteroaryl-(CH 2) m-(A or B)-(CH 2) n; 1-6C alkyl-A-(CH 2) n; 3-7C cycloalkyl-(CH 2) m-A or B)-(CH 2) n; R 2> 1>-A-(CH 2) n; phenyl- or naphthyl-(CH 2) m-D-(1-3C)alkyl; Rb-substituted 2-6C alkyl, or 3-6C cycloalkyl; amino, or arylcarbonylamino; het : pyrrolidin-1-yl, piperidin-1-yl or morpholin-4-yl; R 1> 0>-R 1> 4>, Rb and Rz : various substituents; m : 0-2; n : 1-3; A, B and D : various linking groups; R 2>hydrogen or a wide range of substituents; R 3>various substituents; R 4>a wide range of substituents. The full definitions are given in the DEFINITIONS (Full Definitions) Field. ACTIVITY : Antidiabetic; antiarthritic; antiinflammatory; immunosuppressive; osteopathic; antilipemic; antiarteriosclerosis; anabolic; cardiant; nephrotropic; antinfertility. MECHANISM OF ACTION : Inhibition of dipeptidylpeptidase-IV (DPPIV). The compound (R)-1,3-dimethyl-7-(3-methyl-2-buten-1-yl)-8-(3-aminopiperidin-1- yl)xanthine had IC50 against DDPIV expressed in Caco-2 cells of 22 nM.