New pyrazinopyrimidine or pyrazinoimidazole derivatives useful for weight reduction in mammals, for preventing or treating obesity, type II diabetes or metabolic syndrome and for treating sexual disorders

摘要

Pyrazinopyrimidine or pyrazinoimidazole derivatives (I) are new. Pyrazinopyrimidine or pyrazinoimidazole derivatives of formula (I) and their salts are new; [Image] A1 : an optionally substituted 3- to 12-membered mono-, bi- or spirobicyclic ring optionally containing heteroatoms (N, O, S); n : 0 or 1; m : 0-6; R1 : R8, A'R8, SO 2R8, SO 2A'R8, COR8, COA'R8, CONHR8, CONHA'R8, COOR8, COOA'R8, alkynylene-R8 or (1-4C alkyl)-heterocycle; A' : 1-6C alkylene (optionally substituted with F) or 2-6C alkenylene; R8 : H, halo, OH, CF 3, aryl, heterocyclyl or 3-8C cycloalkyl, the rings being substituted with 0-3 of halo, OH, CF 3, NO 2, CN, OCF 3, OA, A, NH 2, CONR11R12, NR11R12, SO 2Me, COOH, COOA, CONH 2; A : 1-6C alkyl; R11, R12 : H, A, heterocyclyl; R2 : NH 2, NO 2, NR11R12, NH-SO 2-CH3, NH-SO 2-R12, N(R11)SO 2R12, NC(O)R11, optionally substituted heterocyclyl with NHC(O)NR11, or N(1-6C alkyl)N +>(1-4C alkyl) 3; R3-R6 : H, halo, OH, CF 3, CN, NO 2, OCF 3, OA, (1-4C)alkoxy(1-4C)alkoxy, SA, A, 2-6C alkenyl, 3-8C cycloalkyl, 3-8C cycloalkoxy, 3-8C cycloalkenyl, 3-8C cycloalkenyloxy, 2-6C alkynyl, aryl, aryloxy, aryl(1-8C)alkyl, aryl(1-8C)alkoxy, arylthio, NAA, SO 2Me, COOH, COOA, CONAA. An independent claim is also included for medicaments comprising one or more compounds (I) and optionally one or more anorectic agents or statins. ACTIVITY : Anorectic; Antidiabetic. Mice were fasted for 24 hours were treated orally with 6-(4-chlorobenzyl)-1-(2,4-dichlorophenylsulfonyl)-3-dimethylamino-8-isopropyl-hexahydro-pyrazino[1,2-a]pyrimidine-4,7-dione (50 mg/kg) and offered condensed milk after 30 minutes. Cumulative milk consumption over 7 hours was reduced by 31% compared with controls. MECHANISM OF ACTION : None given.