Arilpropionamida analogues, arilacrilamida, arilpropinamida, or arilmetilurea as factor XIa inhibitors

摘要

Relates to compounds of formula (i) where a is a carbociclo (C3 - C10) or a 5 to 12 members heterocycle substituted with 0 - 1 0 - 3 R1 or R2, where R1 IS F, CL, BR, CF3, among others; R2 = o, F, CL, CN, NO2, among Others; L1 is ch2ch2 -, - ch = CH - OCH2, among others; M is a compound of formula (a), (b), among others.Where R3 is - (CH2) R carbociclo (C3 - C10) or (CH2) R - 5 to 12 members heterocycle substituted with 0 or 0 - 1 - 3 R3A R3D, where R3A IS = o, F, I, NO2, among others; R3D is H, F, cn and NO2 among others, R is 0 to 4; R4 is H, F, CL, BR, CF3, among others; R11 is haloalquilo (c1-c4), - C (o) - CH2C ra, RA, (OR) Other, CF3, where ra is H, alkyl (C1 - C6), among others.Preferred compounds are: n {- (S) - 1 - [4 - (3 - amino - 1H - indazol - 6 - 5 - Chloro - yl) - 1H imidazole - 2 (IL - 2 - phenyl] - 3 - (ethyl} - 2.4 - difluoro - phenyl) - propionamide, N - {(S) - 1 - [4 - (3 - amino - 1H - indazol - 6 - 5 - Chloro - yl) - 1H imidazole - 2 (IL - 2 - ethyl] phenyl] - 3 - (2 - methoxy phenyl) - propionamide, N - [(S) - 1 - [4 - (3 - amino - 1H - indazol - 6 - 5 - Chloro - il) 1h imidazole - 2 (IL - 2 - ethyl] phenyl] - 3 - (2 - chloro phenyl) - propionamide, among others.It also relates to a Pharmaceutical Composition and a preparation method. These compounds are Selective inhibitors of the Enzyme serine protease of the coagulation Cascade as factor XIa, thrombin, factor Xa, among others, being useful for the treatment of thromboembolic Disorders such as unstable angina, atherosclerosis, thrombosis, Thrombophlebitis