New (hetero)aryl-substituted carboxamide compounds, are factor Xa and factor VIIa inhibitors useful e.g. for treating thrombosis, myocardial infarction, arteriosclerosis, inflammation or tumors

摘要

(Hetero)aryl-carbamoyloxy- or (hetero)aryl-ureido-carboxylic acid N-substituted amide derivatives (I) are new. Carboxamides of formula (I) and their derivatives, solvates and stereoisomers (including mixtures in all proportions) are new. D = phenyl, pyridyl or thienyl (all optionally substituted by one or more of halo, A, OR2, N(R2)2, NO2, CN, COOR2 or CON(R2)2); X = NR3 or O; R1 = H, Ar, Het, cycloalkyl or A (optionally substituted by OR2, S(O)mR2, N(R2)2, Ar, Het, cycloalkyl, CN, COOR2 or CON(R2)2); R2 = H, A, -(C(R3)2)n-Ar, -(C(R3)2)n-Het, -(C(R3)2)n-cycloalkyl, -(C(R3)2)n-N(R3)2 or -(C(R3)2)n-OR3; R3 = H or A; W = -(C(R3)2)n-; Y = alkylene, cycloalkylene, Het-diyl or Ar-diyl; T = mono- or bicyclic saturated, unsaturated or aromatic carbocycle or heterocycle, containing 0-4 of N, O and/or S, substituted by 1-2 =S, =NR2, =NOR2, =NCOR2, =NCOOR2, =N-CN or =N-NO2 and optionally substituted by 1-3 halo, A, -(C(R3)2)n-Ar, -(C(R3)2)n-Het, -(C(R3)2)n-cycloalkyl, OR3, N(R3)2, NO2, CN, COOR2, CON(R2)2, NR2COA, NR2CON(R2)2, NR2SO2A, COR2, SO2NR2 and/or S(O)nA; A = 1-10C alkyl, optionally having 1 or 2 CH2 groups replaced by O, S and/or CH=CH and optionally substituted by 1-7 F; Ar = phenyl, naphthyl or biphenylyl (all optionally substituted by 1-3 halo, A, OR3, N(R3)2, NO2, CN, COOR3, CON(R3)2, NR3COA, NR3CON(R3)2, NR3SO2A, COR3, SO2N(R3)2, S(O)mA, -(C(R3)2)q-COOR21 or -O-(C(R3)2)q-COOR21); R21 = H, A, -(C(R3)2)n-Ar', -(C(R3)2)n-Het', -(C(R3)2)n-cycloalkyl, -(C(R3)2)n-N(R3)2 or -(C(R3)2)n-OR3; Ar' = phenyl or benzyl (both optionally substituted by 1-2 halo or A); Het = mono- or bicyclic saturated, unsaturated or aromatic heterocycle containing 1-4 N, O and/or S, optionally substituted by 1-3 =O, =S, =N(R3)2, halo, A, -(C(R3)2)n-Ar, -(C(R3)2)n-Het', -(C(R3)2)n-cycloalkyl, -(C(R3)2)n-OR21, -(C(R3)2)n-N(R21)2, NO2, CN, -(C(R3)2)n-COOR21, -(C(R3)2)n-CON(R21)2, -(C(R3)2)n-NR21COA, NR21CON(R21)2, -(C(R3)2)n-NR21SO2A, COR21, SO2NR21 and/or S(O)mA; Het' = mono- or bicyclic saturated, unsaturated or aromatic heterocycle containing 1-2 N, O and/or S, optionally substituted by 1-2 =O, =S, =N(R3)2, halo, A, OR211, N(R211)2, NO2, CN, COOR211, CON(R211)2, -NR211COA, NR211CON(R211)2, NR211SO2A, COR211, SO2NR211 and/or S(O)mA; R211 = H, A, -(C(R3)2)n-Ar', -(C(R3)2)n-cycloalkyl, -(C(R3)2)n-N(R3)2 or -(C(R3)2)n-OR3; m, n = 0-2; and q = 1-3. An Independent claim is also included for the preparation of (I).