New heterocyclic-substituted phenyl compounds, are Factor Xa and Factor VIIa inhibitors useful e.g. for treating thrombosis, myocardial infarction, inflammation, restenosis or tumor diseases

摘要

Heterocyclic-substituted phenyl compounds (I) are new. Heterocyclic-substituted phenyl compounds of formula (I) and their salts, solvates and stereoisomers are new; R1 = H, CN, -C(=NH)NH2 (optionally monosubstituted by COR3, COOR3, OR3 or a conventional amino-protecting group). CON(R3)2, -(C(R4)2)n-N(R3)2, 5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl or 5-methyl-1,2,4-oxadiazol-3-yl; R2, R'2, R''2 = H, halo, A, OR3, N(R3)2, NO2, CN, -(C(R4)2)n-Ar, -(C(R4)2)n-Het, -(C(R4)2)n-cycloalkyl, =C(R4)-(C(R4)2)n-CON(R3)2, -(C(R4)2)n-COOR3, -(C(R4)2)n-CON(R3)2, -O-(C(R4)2)n-COOR3 or -O-(C(R4)2)n-CON(R3)2; R3 = H, A, -(C(R4)2)n-Ar, -(C(R4)2)n-Het or -(C(R4)2)n-cycloalkyl; R4 = H or A; W = N, CR3 or sp2-hybridized C; E = group completing a 3-7 membered saturated carbocycle or heterocycle containing 0-3 N, 0-2 O and/or 0-2 S, which optionally (i) contains a double bond, (ii) is fused with a benzene ring or a saturated, unsaturated or aromatic heterocycle and/or (iii) is substituted by =O; X = -(C(R4)2)n-CONR3-(C(R4)2)n-, -(C(R4)2)n-NR3CO-(C(R4)2)n-, -(C(R4)2)n-NR3-(C(R4) 2)n- or -(C(R4)2)n-O-(C(R4)2)n-; Y = alkylene, cycloalkylene, Het-diyl or Ar-diyl; T = saturated or unsaturated, mono- or bicyclic heterocyclyl, containing 1-4 N and/or 1-4 S and/or 1-4 O, substituted by 1 or 2 =O and optionally further substituted by 1-3 of halo, A, -(C(R4)2)n-Ar, -(C(R4)2)n-cycloalkyl, OR3, N(R3)2, NO2, CN, COOR3, CON(R3)2, NR3COA, NR3CON(R3)2, NR3SO2A, COR3, SO2NR3 or S(O)mA; A = 1-6C alkyl, optionally having at least one CH2 replaced by O or S and optionally substituted by 1-7 F; Ar = phenyl, naphthyl or biphenylyl (all optionally substituted by halo, A, OR4, N(R4)2, NR4CON(R4)2, NO2, CN, COOR4, CON(R4)2, NR4COA, NR4SO2A, COR4, SO2NR4 or S(O)mA); Het = saturated, partially unsaturated or aromatic, mono- or bicyclic heterocyclyl, containing 1-4 N, S and/or O and optionally substituted by 1-3 of halo, A, -(C(R4)2)n-Ar, -(C(R4)2)n-Het', -(C(R4)2)p-cycloalkyl, -(C(R4)2)n-CON(R3)2, -(C(R4)2)n-COOR3, OR3, N(R3)2, NR3CON(R3)2, NO2, CN, NR3COA, NR3SO2A, COR3, SO2NR3, S(O)mA and/or =O); Het' = saturated, partially unsaturated or aromatic, mono- or bicyclic heterocyclyl, containing 1-4 N, S and/or O and optionally substituted by 1 or 2 of halo, A, OR3, N(R3)2, NO2, CN, COOR3, CON(R3)2, NR3COA, NR3SO2A, COR3, SO2NR3, S(O)mA and/or =O); m, n = 0-2.. An Independent claim is also included for the preparation of (I).