Patent DE-102004060041-A1 (DE)
Title: Use of substituted cyclopropane acid derivative having dopamine receptor ligand activity to e.g. treat metabolic syndrome; reduce lipid in the plasma; lower free fatty acid in the plasma; and treat diabetic dyslipidemia
Inventor: KADEREIT DIETER
IPC: A61P3/06
Filed: 2004-12-14
Abstract: Use of substituted cyclopropane acid derivative (I) or its salts for the manufacture of a medicine to treat metabolic syndrome. Use of substituted cyclopropane acid derivative of formula (I) or its salts for the manufacture of a medicine to treat metabolic syndrome. R 1>1-20C alkyl, 2-20C alkenyl, 2-20C alkynyl, aryl, heterocyclyl (all optionally substituted with one more T1 or T2), or H; T1 : F, Cl, Br, I, CF 3, NO 2, N 3, CN, COOH, COO(1-6C alkyl), CONH 2, CONH (1-6C alkyl), CON(1-6C alkyl) 2, cycloalkyl, 1-10C alkyl, 2-6C alkenyl, 2-6C alkynyl, O-(1-6C alkyl), O-CO-(1-6C alkyl), O-CO-(1-6C aryl) (sic), O-CO-(1-6C) heterocyclyl; PO 3H 2, P(O)(O-alkyl) 2, 1-6C alkylene-P(O)(O-alkyl) 2, O-P(O)(OH) 2, O-P(O)(O-alkyl) 2, SO 3H, SO 2-NH 2, SO 2NH(1-6C alkyl), SO 2N(1-6C alkyl) 2, S-(1-6C alkyl), S-(CH 2) n-aryl, S-(CH 2) n-heterocyclyl, SO-(1-6C alkyl), SO-(CH 2) n-aryl, SO-(CH 2) n-heterocyclyl, SO 2-(1-6C alkyl), SO 2-(CH 2) n-aryl, SO 2-(CH 2) n-heterocyclyl, SO 2-NH(CH 2) n-aryl, SO 2-NH(CH 2) n-heterocyclyl, SO 2-N(1-6C alkyl)(CH 2) n-aryl, SO 2-N(1-6C alkyl)(CH 2) n-heterocyclyl, SO 2-N((CH 2) n-aryl) 2 or SO 2-N((CH 2) n-(heterocyclyl) 2, (where aryl or hetercyclyl is optionally substituted with 1-2 substituents chosen from F, Cl, Br, OH, CF 3, SF 5, NO 2, CN, OCF 3, O-(1-6C alkyl), 1-6C alkyl and NH 2); T2 : C(NH)(NH 2), NH 2, NH-(1-6C alkyl), N(1-6C alkyl) 2, NH(1-7C acyl), NH-CO-(1-6C alkyl), NH-COO-(1-6C alkyl), NH-CO-aryl, NH-CO-heterocyclyl, NH-COO-aryl, NHCOO-heterocyclyl, NH-CO-NH-(1-6C alkyl), NH-CO-NH-aryl, NH-CO-NH-heterocyclyl, N[(1-6C alkyl)]-CO-(1-6C alkyl), N(1-6C alkyl)-COO-(1-6C alkyl), N[(1-6C alkyl)]-CO-aryl, N[(1-6C alkyl)]-CO-heterocyclyl, N[(1-6C alkyl)]-COO-aryl, N[(1-6C alkyl)]-COO-heterocyclyl, N[(1-6C alkyl)]-CO-NH-(1-6C alkyl), N[(1-6C alkyl)]-CO-NH-aryl, N[(1-6C alkyl)]-CO-NH-heterocyclyl, N[(1-6C alkyl]-CO-N((1-6C alkyl) 2, N[(1-6C alkyl)]-CO-N(1-6C alkyl)-aryl, N[(1-6C alkyl)]-CO-N(1-6C alkyl)-heterocyclyl, N(1-6C alkyl)-CO-N(aryl) 2, N(1-6C alkyl)-CO-N(heterocyclyl) 2, N(aryl)-CO-(1-6C alkyl), N(heterocyclyl)-CO-(1-6C alkyl), N(aryl)-COO-(1-6C alkyl), N(heterocyclyl)-COO-(1-6C alkyl), N(aryl)-CO-aryl, N(heterocyclyl)-CO-aryl, N(aryl)-COO-aryl, N(heterocyclyl)-COO-aryl, N(aryl)-CO-NH-(1-6C alkyl), N(heterocyclyl)-CO-NH-(1-6C alkyl), N(aryl)-CO-NH-aryl, N(heterocyclyl)-CO-NH-aryl, N(aryl)-CO-N(1-6C alkyl) 2, N(heterocyclyl)-CO-N(1-6C alkyl) 2, N(aryl)-CO-N(1-6C alkyl)-aryl, N(heterocyclyl)-CO-N(1-6C alkyl]-aryl, N(aryl)-CO-N(aryl) 2, N(heterocyclyl)-CON(aryl) 2, aryl, O-(CH 2) n-aryl or O-(CH 2) n-heterocyclyl (where the aryl- or heterocyclyl- residue is substituted with 1-3 substituents of F, Cl, Br, I, OH, CF 3, NO 2, CN, OCF 3, O-(1-6C alkyl), 1-6C alkyl, NH 2, NH(1-6C alkyl), N(1-6C alkyl) 2, SF 5, SO 2-CH 3, COOH, COO-(1-6C alkyl) or CONH 2); R 2>1-20C alkyl, 2-20C alkenyl, 2-20C alkynyl, aryl, 3-7C cycloalkyl, heterocyclyl (all substituted with T1 or T2); R 3>-R 6>H, F, Cl, Br, I, OH, CF 3, NO 2, CN, OCF 3, 1-6C alkyl or O-(1-6C alkyl); and n : 0-6. [Image] ACTIVITY : Antidiabetic; Antilipemic; Vasotropic; Antiarteriosclerotic; Cardiant; Cerebroprotective; Anticoagulant; Thrombolytic; Hypotensive; Cardiovascular-Gen.; Analgesic; Antianginal. The ability of (I) lower free fatty acid, glycerol or triglyceride in the plasma was tested using biological assays. The results showed that 1R-methoxycarbonyl-2R-hydroxycarbonylcyclopropane exhibited a median effective concentration value of 0.07 mu M. MECHANISM OF ACTION : Dopamine receptor ligand.