FARNESYL TRANSFERASE INHIBITING 1,8-ANNELATED QUINOLINONE DERIVATIVES SUBSTITUTED WITH N- OR C-LINKED IMIDAZOLES, THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS COMPRISING THEM

摘要

Anticancer compounds of the formula pharmaceutically acceptable acid addition salts or stereochemically isomeric forms thereof, wherein the dotted line is null if R' is H, and otherwise represents an optional bond, X is oxygen or sulfur; -A- is a bivalent radical of the formula -CH=CH--CH2-S- -CH2-CH2--CH2-CH2-S- -CH2-CH2-CH2-CH=N- -CH2-O--N=N- -CH2-CH2-O--CO-NH- 3647 כ" ז בשבט התשס" ד - February 19, 2004 wherein optionally one hydrogen atom may be replaced by C1-4 alkyl or Ar1; R1 and R2 each independently are hydrogen, hydroxy, halo, cyano, C1-6 alkyl, trihalomethyl, trihalomethoxy, C2-6 alkenyl, C1-6 alkyloxy, hydroxy C1-6 alkyloxy, C1-6 alkyloxy C1-6 alkyloxy, C1-6 alkyloxycarbonyl, amino C1-6 alkyloxy, mono- or di(C1-6 alkyl) amino C1-6 alkyloxy, Ar2, Ar2-C1-6alkyl, Ar2-oxy, Ar2-C1-6 alkyloxy; or when on adjacent positions R1 and R2 taken together may form a bivalent radical of formula -O-CH2-O- -O-CH2-CH2-O- -O-CH=CH- -O-CH2-CH2- -O-CH2-CH2-CH2- -CH=CH-CH=CH- R3 and R4 each independently are hydrogen, halo, cyano, C1-6 alkyl, C1-6 alkyloxy, Ar3-oxy, C1-6 alkylthio, di(C1-6 alkyl) amino, trihalomethyl, trihalomethoxy, or when on adjacent positions R3 and R4 taken together may form a bivalent radical of the formula -O-CH2-O- -O-CH2-CH2-O- -CH=CH-CH=CH- R5 is a radical of the formula wherein R13 is hydrogen, halo, Ar4, C1-6 alkyl, hydroxy C1-6 alkyl, C1-6 alkyloxy C1-6 alkyl, C1-6 alkyloxy, C1-6 alkylthio, amino, C1-6 alkyloxycarbonyl, C1-6 alkyl S(O)C1-6 alkyl or C1-6 alkyl S(O)2C1-6 alkyl; R14 is hydrogen, C1-6 alkyl or di(C1-4 alkyl) aminosulfonyl; R6 is hydrogen, hydroxy, halo, C1-6 alkyl, cyano, halo C1-6 alkyl, hydroxy C1-6 alkyl, cyano C1-6 alkyl, amino C1-6 alkyl, C1-6 alkyloxy C1-6 alkyl, C1-6 alkylthio C1-6 alkyl, aminocarbonyl-C1-6 alkyl, C1-6 alkyloxycarbonyl C1-6 alkyl, C1-6 alkylcarbonyl C1-6 alkyl, C1-6 alkyloxycarbonyl, mono- or di(C1-6 alkyl) amino C1-6 alkyl, Ar5, Ar5-C1-6 alkyloxy C1-6 alkyl; or a radical of the formula -O-R7 -S-R7 or -N-R8R9 wherein R7 is hydrogen, C1-6 alkyl, C1-6 alkylcarbonyl, Ar6, Ar6-C1-6 alkyl, C1-6 alkyloxycarbonyl C1-6 alkyl, or a radical of formula -Alk-OR10 or -Alk-NR11R12 R8 is hydrogen, C1-6 3648 כ" ז בשבט התשס" ד - February 19, 2004 alkyl, Ar7 or Ar7-C1-6 alkyl; R9 is hydrogen, C1-6 alkyl, C1-6 alkylcarbonyl, C1-6 alkyloxycarbonyl, C1-6 alkylaminocarbonyl, Ar8, Ar8-C1-6 alkyl, C1-6 alkylcarbonyl-C1-6 alkyl, Ar8-carbonyl, Ar8-C1-6 alkylcarbonyl, aminocarbonylcarbonyl, C1-6 alkyloxy C1-6 alkylcarbonyl, hydroxy, C1-6 alkyloxy, aminocarbonyl, di(C1-6 alkyl) amino C1-6 alkylcarbonyl, amino, C1-6 alkylamino, C1-6 alkylcarbonylamino, or a radical of formula -Alk-OR10 or -Alk-NR11R12; wherein Alk is C1-6 alkanediyl; R10 is hydrogen, C1-6 alkyl, C1-6 alkylcarbonyl, hydroxy C1-6 alkyl, Ar9 or Ar9-C1-6 alkyl; R11 is hydrogen, C1-6 alkyl, C1-6 alkylcarbonyl, Ar10 or Ar10C1-6 alkyl; R12 is hydrogen, C1-6 alkyl, Ar11 or Ar11-C1-6 alkyl; and Ar1 to Ar11 are each independently selected from phenyl; or phenyl substituted with halo, C1-6 alkyl, C1-6 alkyloxy or trifluoromethyl; wherein R' is H,