Patent FR-2889190-A1 (FR)
Title: New imidazole carboxamides, useful to treat e.g. pathologies associated with the insulin resistance syndrome, are fructose-1,6-biphosphatase inhibitors
Inventor: MOINET GERARD
IPC: C07D233/90
Filed: 2005-08-01
Abstract: Imidazole carboxamides (I) are new. Imidazole carboxamides of formula (I) and their tautomers, enantiomers, diastereoisomers, epimers and organic or mineral salts are new. R = OH, OR 15> or NR 11>R 12>; R 11>, R 12> = H or Z; or NR 11>R 12> = ring containing 1-3 heteroatoms, optionally fused and/or optionally substituted by 1-3 Y 1>; R 15> = 1-8C alkyl, 2-20C alkenyl, 2-20C alkynyl, 3-8C cycloalkyl (all optionally substituted by T 1>), 3-8C heterocycloalkyl (containing N, O or S and optionally substituted by halo, 1-8C alkyl or 1-8C alkoxy), 6-14C (hetero)aryl or or 6-14C (hetero)aryl(1-20C alkyl) (both optionally substituted by T 2>); T 1> = halo, 1-8C alkyl, 1-8C alkoxy, 3-8C cycloalkyl or 6-14C aryl; T 2> = amino, OH, SH, halo, 1-8C alkyl, 1-8C alkoxy, 1-8C alkylthio, 1-8C alkylamino, 6-14C aryl, 6-14C aryloxy or 6-14C aryl(1-8C alkoxy); R 1> = C(O)R 2> or C(O)NHR 2>; R 2> = Z; A = bond or divalent radical obtained by removal of one H from 1-20C alkyl, 2-20C alkenyl, 2-20C alkynyl, 1-20C alkoxy, 1-20C alkoxy(1-20C alkyl), 1-20C alkylthio, 1-20C alkylthio(1-20C alkyl), 1-20C alkylamino or 1-20C alkylamino(1-20C alkyl) (all optionally substituted by one or more Y 1>); D = bond or divalent radical obtained by removal of one H from 1-20C (oxy)alkyl, 2-20C (oxy)alkenyl, 2-20C (oxy)alkynyl, 1-20C alkoxy(1-20C alkyl), 1-20C alkylthio(1-20C alkyl), 1-20C alkylamino(1-20C alkyl), 1-20C thioalkyl, 2-20C (thio)alkenyl or 2-20C (thio)alkynyl (all optionally substituted by one or more Y 1>); X = bond or divalent radical obtained by removal of one H from 6-14C aryl, 5-14C heteroaryl (optionally containing O, N or S), 3-8C alkyl, 4-8C cycloalkenyl, 3-8C heterocycloalkyl (optionally containing O, N or S) (all optionally substituted by one or more Y 1>); or AXD = bond; Y 1> = OH, SH, halo, CN, OCF 3, CF 3, COOH, carboxymethyl, carboxyethyl, 1-8C alkyl, 1-8C alkoxy, 1-8C alkylamino, 6-14C aryl, 6-14C arylsulfonyl(1-8C alkyl), 6-14C aryloxy, 6-14C aryl(1-14C alkoxy), amino, azido, nitro, guanidino, amidino, phosphono, O, carbamoyl, 1-8C alkylsulfonyl, 1-8C alkylsulfinyl or 1-8C alkylthio; or Y 1>Y 1> = methylenedioxy; and Z = 6-14C (hetero)aryl, 6-14C (hetero)aryl-1-20C (oxy)alkyl, 6-14C (hetero)aryl(1-20C alkoxy)1-20C alkyl, 6-14C (hetero)aryl(1-20C thioalkyl), 6-14C (hetero)aryl(1-20C alkyl)1-20C thioalkyl, 3-8C (hetero)cycloalkyl, 3-8C (hetero)cycloalkyl(1-20C (oxy)alkyl), 3-8C (hetero)cycloalkyl(1-20C alkoxy)1-20C alkyl, 3-8C (hetero)cycloalkyl(1-20C thioalkyl), 3-8C (hetero)cycloalkyl(1-20C alkyl)1-20C thioalkyl, (6-14C (hetero)aryl)2-20C alkenyl, (6-14C (hetero)aryl)2-20C alkynyl (all optionally contain N, O or S) or 1-20C alkyl (all optionally substituted by one or more Y 1>). An independent claim is included for preparation of (I). [Image] ACTIVITY : Antidiabetic; Cardiovascular-Gen.; Antiarteriosclerotic; Cardiant; Antilipemic. MECHANISM OF ACTION : Fructose-1,6-biphosphatase inhibitor. The ability of (I) to inhibit fructose-1,6-biphosphatase was tested in human liver recombinant fructose-1,6-biphosphatase. Results showed that 5-[5-(4-tert-butylbenzoylamino)-4-carbamoyl-1H-imidazol-2-ylmethyl]furan-2-carboxylic acid exhibited IC 50 of 23 mu M.