New (hetero)aryl-guanidine or -amidine compounds, are potent and selective urokinase-plasminogen activator inhibitors, useful for treating tumors or metastasis formation

摘要

(Hetero)aryl-guanidine or -amidine compounds (I) are new. (Hetero)aryl-guanidine or -amidine compounds of formula (I) are new. Ar = aromatic or heteroaromatic ring system; E = H2N-C(=NH)-NH- or H2N-C(=NH)-; or Ar+E = fused heteroaromatic group of formula (i) or (ii); Z' = O, NH or CO; B' = SO2, C(R3)2, NR3 or NH; R2 = halo, C(R6)3, C2(R6)5, OC(R6)3 or OC2(R6)5; X1 = NR13R4, OR3, SR3, COOR3, CONR3R4 or COR5; X4 = CO, NH or CH2; W = N, CR3 or CR6; X5 = CH, CR3, CR6 or N; R3 = H or organic group; R13 = -R15-(Y)n-X3-R7 or -R15-(Y)n-NH-CO-CH(R10)-N(R1)-R11; R1 = H; alkyl, alkenyl, alkynyl, aryl or heteroaryl (all optionally substituted (os)); or COOR3, CONR3R4 or COR5; X3 = NH, NR4, O, S, CO, COO, CONH or CONR4; Y = C(R8)2, NH or NR3; R4 = H; or alkyl, alkenyl or alkynyl (all os); R5 = H, alkyl, alkenyl, alkynyl, carboxy-alkyl, carboxy-alkenyl, carboxy-alkynyl, carboxy-aryl, carboxy-heteroaryl, -(CO)NR3R4 or COOR3 (where the alkyl, aryl and heteroaryl moieties are os); R6 = H or halo (especially F); R7 = H; alkyl, alkenyl, alkynyl, aryl or heteroaryl (all os); or COR9; R8 = H; or alkyl, alkenyl, alkynyl, aryl, heteroaryl, aralkyl, alkaryl, heteroaralkyl or bi- or polycyclic residue (all os); R9 = H; or alkyl, alkenyl, alkynyl, aryl or heteroaryl (all os); R10 = -C(R1)2)q-X3-R5; R11 = H, COR12, CON(R12)2, COOR12 or preferably SO2R12; R12 = H; or alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, aralkyl, alkaryl, heteroaralkyl or bi- or polycyclic residue (all os); R15 = C=X2, NR3 or C(R3)2; X2 = NH, NR4, O or S; n = 0-2; m = 0-5; and p, q = 1-5.