New 2-(naphthalen-2-ylmethyl)-benzimidazole derivatives are Factor VIIa, IXa, Xa and thrombin inhibitors useful for treating thrombosis and other cardiovascular disorders, inflammation and apoplexy

摘要

2-(Naphthalen-2-ylmethyl)-benzimidazole derivatives (I) are new. 2-(Naphthalen-2-ylmethyl)-benzimidazole derivatives of formula (I) and their salts are new. Q = H, COOR1, R, H, A, (CH2)n-Ar, Ar or Het; R1 = H, A, (CH2)n-Ar or Ar; R2 = H, CN, C(=NH)-A, C(=NH)-NH2, C(=NH)-NH-NH2, C(=NH)-CH2-COOR5, C(=NH)-CH2-N(R5)2, 2-pyrrolin-2-yl or 5-methyl-1,2,4-oxadiazol-3-yl; R3 = CN, C(=NH)-NHR4, 2-pyrrolin-2-yl or 5-methyl-1,2,4-oxadiazol-3-yl; R4 = H, NH2 or OH; R5 = H or A; R6 = A, (CH2)n-Ar, Ar or Het; X = NHCO, N(SO2R6), NHCH2 or NH; A = 1-6C alkyl; Ar = phenyl optionally substituted by 1-3 A, OH, OA, NH2, NHA, NA2, NO2, CN, Hal, COOH, COOA, CONH2, CONHA, CONA2, COA, S(O)nA or S(O)Ar groups; Het = mono- or bi-cyclic heterocyclyl with 1-4 O, N and/or S heteroatoms, optionally substituted by 1-3 Hal, A, OH, OA, COOH, COOA, CN, NO2, NH2, NHA or NA2 groups; Hal = F, Cl, Br or I and n = 1 or 2, provided that when X = NH, R2 = C(=NH)-NH-NH2, C(=NH)-CH2-COOR5, C(=NH)-CH2-N(R5)2 or 2-pyrrolin-2-yl and when X = NH, R2 may also be C(=NH)-A so long as R4 = NH2.