SUBSTITUTED BIPHENYL DERIVATIVES

摘要

Amidino-aryl substituted biphenyl derivatives and analogs (I) are new. Amidino-aryl substituted biphenyl derivatives of formula (I), their salts or solvates, are new. [Image] R1phenyl or naphthyl, both (i) substituted by -C(=NH)NH2 (optionally mono-substituted by COA, CO(C(R7)2)n-Ar', COOA, OH or an amino-protecting group), NHC(=NH)NH2, CON=C(NH2)2, 5-methyl-1,2,4-oxadiazol-3-yl or 5-oxo-4,5-dihydro-1,2,4-oxadiazol-3 -yl and (ii) optionally substituted by A, OR5, N(R5)2, NO2, CN, halo, NR5COA, NR5COAr', NR5SO2A, NR5SO2Ar', COOR5, CON(R5)2, COR7, COAr' or S(O)nA; R2S(O)nA, CF3, COOR7 or OA; R3, R4H, A, OR5, N(R5)2, NO2, CN, halo, NR5COA, NR5COAr', NR5SO2A, NR5SO2Ar', COOR5, CON(R5)2, CON(R5)Ar', COR7, COAr' or S(O)nA; R5, R6H, A, (CR7R8)nAr' or (CR7R8)nHet; R7, R8H or A; W : (CR5R6)m-CO-NR5-(CR5R6)l or O(CR5R6)m-CO-NR5-(CR5R6)l; 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 napthyl (both optionally substituted by 1-3 of A, Ar', Het, OR5, N(R5)2, NO2, CN, halo, NR5COA, NR5COAr', NR5SO2A, NR5SO2Ar', COOR5, CON(R5)2, CON(R5)Ar', COR7, COAr', SO2NR5, S(O)nAr' or S(O)nA); Ar' : phenyl or napthyl (both optionally substituted by 1-3 of A, OR7, N(R7)2, NO2, CN, halo, NR7COA, NR7SO2A, COOR7, CON(R7)2, COR7, SO2NR7 or S(O)nA); Het : C- or N-bonded, mono- or bicyclic, saturated, unsaturated or aromatic heterocycle containing 1-4 of O, S and N (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 =O); l : 0 or 1; m : 1 or 2; and n : 0-2. - ACTIVITY : Thrombolytic; anticoagulant; cardiant; antiarteriosclerotic; antiinflammatory; cerebroprotective; antianginal; vasotropic. No biological data given. - MECHANISM OF ACTION : Factor Xa inhibitor; activated serine protease inhibitor; Factor VIIa inhibitor; Factor IXa inhibitor; thrombin inhibitor.