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.
