New 1-benzoyl-3-(heterocyclyl-phenyl)-urea derivatives, are glycogen phosphorylase a inhibitors useful e.g. for treating type II diabetes, dyslipidemia or arteriosclerosis

摘要

1-Benzoyl-3-(heterocyclyl-phenyl)-urea derivatives (I) are new. Benzoylurea derivatives of formula (I) and their salts are new. [Image] R 1, R 2H, alkyl (optionally substituted by OH, OT, NH 2, NHT or dialkylamino), alkoxy, alkylcarbonyl, alkoxycarbonyl, carboxyalkyl or alkoxycarbonylalkyl; T : 1-4C alkyl; R 3, R 4F, Cl, Br, OH, NO 2 or CN; or alkyl, OT, alkenyloxy or alkynyl (all optionally multiply substituted by F, Cl or Br); R 5H, F, Cl, Br, OH, NO 2, CN or COOH; or alkyl, OT, alkylcarbonyl, carboxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, alkylsulfonyl, alkenyloxy or alkynyl (all optionally multiply substituted by F, Cl or Br); A : H, F, Cl, Br, OH, NO 2, CN, COOH, CONH 2, SO 2NH 2 or NHCOR 6; or alkyl, alkylcarbonyl, carboxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, alkylsulfonyl, alkenyl, alkynyl, alkoxy, alkylsulfinyl, mono- or dialkylaminocarbonyl, mono- or dialkylaminosulfonyl (all optionally multiply substituted by F, Cl, Br, COOH, alkoxycarbonyl, CONH 2, mono- or dialkylaminocarbonyl or alkylcarbonyloxy); R 6H, alkyl, cycloalkyl, cycloalkyl-(1-4C) alkyl, alkenyl, alkynyl, alkoxycarbonylalkyl, alkylcarbonylalkyl, COOH, carboxyalkyl, carbamoylalkyl, 6-10C aryl, (6-10C) aryl-(1-4C) alkyl, heteroaryl, heteroaryl-(1-4C) alkyl or heteroaryl-carbonyl (where alkyl, cycloalkyl, alkenyl and alkynyl moieites are optionally multiply substituted by F, Cl, Br, OT, COOT or NT 2; and aryl or heteroaryl moieties are optionally multiply substituted by F, Cl, Br, NO 2, CN, OT, SCOOT, NT 2 or alkyl); n, p : 0-3; m : 1-5; Het : 4-7 membered heterocycle containing 1-4 of N, O and/or S as heteroatom(s) (excluding pyrrole), substituted by R 7 - R 9; and R 7 - R 9H, F, Cl, Br, OH, =O, NH 2, COOH or CONH 2; or alkyl, alkoxy, alkenyloxy, alkynyloxy, mono- or dialkylamino, alkylcarbonyl, alkoxycarbonyl, mono- or diaklylaminocarbonyl, aryl, aralkyl or alkoxycarbonylalkyl (all optionally multiply substituted by COOH, CONH 2, mono- or dialkylaminocarbonyl, alkylcarbonyloxy, F, Cl, alkyl or alkoxy); or two of R 7 - R 9 may together complete a fused ring. Alkyl moieties have 1-6C, cycloalkyl moieties 3-7C and alkenyl or alkynyl moieties 2-6C unless specified otherwise. An independent claim is included for the preparation of (I). ACTIVITY : Antidiabetic; Antilipemic; Antiarteriosclerotic. MECHANISM OF ACTION : Glycogen phosphorylase A inhibitor. 1-(2-Chloro-4,5-difluorobenzoyl)-3-(2-methoxy-4-(5-methyl-4H-(1,2,4)-triazol-3-yl)-phenyl)-urea (Ia) at a concentration of 10 MicroM inhibited glycogen phosphorylase a by 100%.