Nuevos derivados de amida del ácido tiazol-4-carboxílico 2-sustituidos, su preparación y uso como medicamentos

摘要

2-Substituted thiazole-4-carboxamide derivatives (I), their salts, enantiomers and diastereomers are new. 2-Substituted thiazole-4-carboxamide derivatives of formula (I), their salts, enantiomers and diastereomers are new. Q 1heteroaryl ring having 5 ring atoms; R 1and R 21-6C alkyl, 2-6C alkenyl, 2-6C alkynyl, 1-6C alkoxy, 1-6C fluoroalkyl or 1-6C fluoroalkoxy (all optionally substituted by at least one 1-3C alkoxy, hydroxy, -C(O)-R 10or -NR 8R 9), H, hydroxy, nitro, halo, cyano, -CF 3, -NR 5R 6, -C(O)-R 10, -C(O)-R 7, -C(O)-1-3C-fluoroalkyl, -C(O)-NR 5R 6, -NH-C(O)-R 7, -O-SO 2-NR 5R 6, -SO 2-R 7, or -SO 2-NR 5R 6; Q 2(hetero)aryl or hydrogenated bicyclic heteroaryl ring; R 3and R 41-6C alkyl or 1-6C alkoxy (both optionally substituted by at least one hydroxy, 1-3C alkoxy, -NR 8R 9or heterocyclyl (optionally substituted by at least one 1-3C alkyl or -C(O)-R 7)), H, halo or -NR 11R 12; R 5, R 6, R 11and R 12H or 1-6C alkyl (optionally substituted by at least one hydroxy, 1-3C alkoxy, -NR 8R 9, or heterocyclyl (optionally substituted by at least one 1-3C alkyl or -C(O)-R 7));or NR 5R 65-7-membered ring (optionally comprises a further heteroatom in addition to the nitrogen atom, and optionally substituted by at least one 1-3C alkyl and/or -C(O)-R 7); R 71-6C alkyl; R 8-R 10H or 1-6C alkyl. In compound (I), A1, B1, C1 and D1 are building blocks and building blocks B1 and D1 are in ortho position relative to one another. [Image] - ACTIVITY : Antiinflammatory; Antiallergic; Cytostatic; Respiratory-Gen.; Antiasthmatic; Antibacterial; Antirheumatic; Immunosuppressive; Antiarthritic; Vasotropic; Dermatological; Muscular-Gen.; Antipsoriatic; Antilichen; Antipruritic; Nephrotropic; Hepatotropic; Gastrointestinal-Gen.; Antiulcer; Ophthalmological; Auditory; Neuroprotective; Cerebroprotective; CNS-Gen.; Nootropic; Antianemic; Hemostatic; Immunostimulant; Endocrine-Gen.; Antithyroid; Antidiabetic; Gynecological. - MECHANISM OF ACTION : Toll-like receptor (TLR) inhibitor; TLR7 inhibitor; TLR9 inhibitor. The efficacy of N-[2-(aminocarbonyl)-5-methylphenyl]-2-(1H-pyrazol-4- yl)-thiazole-4-carboxamide (I') was evaluated for TLR inhibitory activity using Peripheral Blood Mononuclear Cells (PBMC). PBMC with the compound (I') were incubated for 18 hours, in the presence or absence of TLR7 or TLR9 ligands. On the next day, the supernatants were investigated for the content of tumor necrosis factor-alpha (TNF-alpha ) or other cytokines or chemokines. The compound showed EC 5 0of 1.2e-7 mol/l.