Thiophene derivatives of aminoacids, process for the preparation thereof and compositions containing them

摘要

4-Phenyl-2-thiophenecarboxamide derivatives (I) are new. 4-Phenyl-2-thiophenecarboxamide derivatives of formula (I) and their isomers and salts are new. [Image] R1, R2H, halo, CN, NO2, 1-6C haloalkyl, 1-6C haloalkoxy, 1-6C alkyl, 2-6C alkenyl, 2-6C alkynyl, OR4, NR4R5, SOnR4, COR4, COOR4, OCOR4, CONR4R5, NR5COR4, NR5SO2R4, TCN, TOR4, TOCF3, TNR4R5, TSOnR4, TCOR4, TCOOR4, TOCOR4, TCONR4R5, TNR5COR4, TNR5SO2R4, R6 or TR6; n : 0-2; T : 1-6C alkylene (optionally substituted with oxo, halo, 1-6C alkoxy, OH, NH2, 1-6C alkylamino or di(1-6C alkyl)amino and/or in which a C atom is replaced by O, S, NH or 1-6C alkylimino); R4H, 1-6C alkyl, aryl, cycloalkyl or heterocyclyl; R5H or 1-6C alkyl; R6aryl, cycloalkyl or heterocyclyl (all optionally substituted with 1-5 of halo, CN, NO2, oxo, 1-6C haloalkyl, 1-6C haloalkoxy, 1-6C alkyl, 2-6C alkenyl, 2-6C alkynyl, OR4, NR4R5, SOnR4, COR4, COOR4, OCOR4, CONR4R5, NR5COR4, NR5SO2R4, TCN, TOR4, TOCF3, TNR4R5, TSOnR4, TCOR4, TCOOR4, TOCOR4, TCONR4R5, TNR5COR4, orTNR5SO2R4); m, p, q : 0-4; R7aryl, cycloalkyl or heterocyclyl (all optionally substituted with 1-3 of halo, CN, NO2, 1-6C haloalkyl, 1-6C haloalkoxy, 1-6C alkyl, OH, 1-6C alkoxy, NH2, 1-6C alkylamino, di(1-6C alkyl)amino, SH, 1-6C alkylthio, 1-7C acyl, 1-6C alkylsulfinyl, COOH and 1-6C alkoxycarbonyl); R8COOH, 1-6C alkoxycarbonyl, hydroxy(1-6C)alkoxycarbonyl, (1-6C)alkoxy(1-6C)alkoxycarbonyl, tetrazolyl, amino, aminocarbonyl or amino(1-6C)alkylcarbonyl (where the amino portions are optionally mono- or disubstituted with 1-6C alkyl or cycloalkyl); aryl : 4-10C mono- or bicyclic aryl; cycloalkyl : 3-12C mono- or bicycloalkyl (optionally partially unsaturated); heterocyclyl : 3-12-membered mono- or bicyclic heterocyclyl with 1-4 heteroatoms (O, S, N), optionally containing 1-2 oxo or thioxo groups; acyl : COR; and R : alkyl, 3-6C cycloalkyl or phenyl. Independent claims are included for preparing (I). ACTIVITY : Antiinflammatory; Antiasthmatic; Antiallergic; Cytostatic; Osteopathic; Antiarthritic; Antirheumatic; Antiarteriosclerotic; Neuroprotective; Cardiant. MECHANISM OF ACTION : Matrix metalloproteinase-12 (MMP-12) inhibitor; Matrix metalloproteinase-13 (MMP-13) inhibitor (2S)-2-(4-(4-trifluoromethoxyphenyl)-2-thienylcarboxamido)-2-phenylacetic acid had an IC50 of 0.38 mu M for inhibiting MMP-12 cleavage of Mca-Pro-Leu-Gly-Leu-Dap(Dnp)-Ala-Arg-NH2.