New biphenyl-substituted amino-(iso)quinoline derivatives, are factor Xa and factor VIIa inhibitors useful e.g. for treating thrombosis, myocardial infarction, inflammation, angina pectoris or restenosis

摘要

Biphenyl-substituted 1-aminoisoquinoline or 2-aminoquinoline derivatives (I) are new. Quinoline or isoquinoline derivatives of formula (I) and their salts and solvates are new: D=E = N=C(NH2) or C(NH2)=N; R1, R2, R4, R5 = H, A, OR6, N(R6)2, NO2, CN, halo, NR6COA, NR6COAr', NR6SO2A, NR6SO2Ar', COOR6, CON(R6)2, CON(R6)Ar', COR7, COAr' or S(O)nA; R3 = SO2N(R6)2, S(O)nA, CF3, COOR6, OA or CN; R6 = H, A, (C(R7)2)nAr' or (C(R7)2)nHet; R7 = H or A; W = CONR6-C(R6)2-CONR6-(C(R6)2)p, NR6C(R6)2-CONR6-(C(R6)2)p-(C(R6)2)m-CONR6-(C(R6)2)p or OC(R6)2-CONR6-(C(R6)2)p; A = 1-20C alkyl (optionally having 1 or 2 CH2 replaced by O, S or CH=CH and optionally substituted by 1-7 F); Ar = phenyl or naphthyl (both optionally substituted by 1-3 of A, Ar', Het, OR6, N(R6)2, NO2, CN, halo, NR6COA, NR6COAr', NR6SO2A, NR6SO2Ar', COOR6, CON(R6)2, CON(R6)Ar', COR7, COAr', SO2NR6, S(O)nAr' or S(O)nA); Ar' = phenyl or naphthyl (both optionally substituted by 1-3 of A, OR7, N(R7)2, NO2, CN, halo, NR7COA, NR7SO2A, COOR7, CON(R7)2, CON(R6)Ar', COR7, SO2NR7 or S(O)nA); Het = N- or C-bonded, mono- or bicyclic, saturated, unsaturated or aromatic heterocycle containing 1-4 of N, O and/or S as heteroatom(s) (optionally substituted by 1-3 of A, OR7, N(R7)2, NO2, CN, halo, NR7COA, NR7SO2A, COOR7, CON(R7)2, COR7, SO2NR7, S(O)nA or oxo; n = 0 - 2; m = 1 - 2; and p = 0 - 1.