Patent IL-117798-A (IL)
Title: Tricyclic compounds useful for inhibition of g-protein function and for treatment of proliferative diseases and pharmaceutical compositions comprising them
IPC: C07D491/04
Filed: 1996-04-02
Abstract: Compounds of the formula wherein: A and B are independently selected from H, halo or C1-C6 alkyl; Z in N or CH; W is CH, CH2, O or S, wherein the dotted line to W represents a double bond which is present when W is CH; X is C, CH or N, wherein the dotted line connecting X to the tricyclic ring system represents a double bond which is present when X is C; R1 is selected from: (1) a group of the formula: or disulfide dimers thereof; (2) a group of the formula: 2957 י' בכסלו התשס" ב - November 25, 2001 (3) a group of the formula: wherein W, A and B are as defined above; (4) a group of the formula: (5) a group of the formula: wherein R80 is selected from H or -C(O) OR90 wherein R90 is a C1-C6 alkyl group, and R85 is a C1-C6 alkoxy group; and (6) a group of the formula: 2958 י' בכסלו התשס" ב - November 25, 2001 (b) x is 0, 1, 2, 3, 4, 5 or 6; (c) each Ra and each Rb is independently selected from H, aryl, alkyl, alkoxy, aralkyl, amino, alkylamino, heterocycloalkyl, -COOR60, -NH{C(O)}zR60 (wherein z is 0 or 1), or -(CH)wS(O)mR60 (wherein w is 0, 1, 2 or 3, and m is 0, 1 or 2); or Ra and Rb taken together can represent cycloalkyl, =N-O- alkyl, =O or heterocycloalkyl with the proviso that for the same carbon, Ra is not selected from alkoxy, amino, alkylamino or -NH{C(O)}zR60 when Rb is selected from alkoxy, amino, alkylamino or -NH{C(O)}zR60; and with the proviso that when T is a single bond, for the first carbon containing Ra and Rb, Ra and Rb are not selected from alkoxy, alkylamino, amino or -NHR60; and (d) R92 can represent H, alkyl, aryl, aryloxy, arylthio, aralkoxy, aralkyl, heteroaryl or heterocycloalkyl; R60 represents H, alkyl, aryl or aralkyl; R4 is H or C1-C6 alkyl; R2 is selected from: H, -C(O)OR6, -C(O) NR6R7, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, substituted (C1-C8 alkyl, substituted (C2-C8) alkenyl, substituted (C2-C8) alkynyl, wherein said substituted groups have one or more substituents selected from: (1) aryl, arylalkyl, heteroarylalkyl, heteroaryl, heterocycloalkyl, B-substituted aryl, B-substituted arylalkyl, B-substituted heteroarylalkyl, B-substituted heteroaryl or B-substituted heterocycloalkyl, wherein B is selected from C1-C4 alkyl, -(CH2)nOR6, -(CH2)nNR6R7 and halo; (2) C3-C6 cycloalkyl; (3) -OR6; (4) -SH or -S(O)tR6; (5) -NR6R7; (6) -N(R6)-C(O)R7; (7) -N(R6)-C(O)NR7R12; (8) -O-C(O)NR6R7; (9) -O-C(O)OR6; (10) -SO2NR6R7; (11) -N(R6)-SO2-R7; (12) -C(O)NR6R7; (13) -C(O)OR6; and provided R2 is not H wherein R1 is -C(O)-CH2-R5, -C(O)-O-R5 or -C(O)-NH-R5, wherein R5 is pyridyl, pyridyl N-oxide, 2959 י' בכסלו התשס" ב - November 25, 2001 or a piperidinyl group of the formula wherein R11 represents H, C1-C6 alkyl, haloalkyl or -C(O)-R9 wherein R9 is C1-C6 alkyl, C1-C6 alkoxy or -NH(R10) wherein R10 is H or alkyl, or the group -C(O)-R9 represents an acyl radical of a naturally occurring amino acid; R6, R7 and R12 are independently selected from H, C1-C4 alkyl, (C3-C6) cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl, substituted (C1-C4) alkyl, substituted (C3-C6) cycloalkyl, substituted aryl, substituted arylalkyl, substituted heteroaryl, substituted groups have one or more substituents selected from: C1-C4 alkoxy, aralkyl, heteroarylalkyl, -NO2, C3-C10-alkoxyalkoxy, C3-C6 cycloalkyl, aryl, -CN, nitrophenyl, methylenedioxy- phenyl, heteroaryl, heterocycloalkyl, halo, -OH, -C(O)R14, -C(O)NR6R7, -N(R6)C(O)R14, -S(O)tR14 or -NR95R15; provided that R6, R7 and R12 are not -CH2OH or -CH2NR95R14 when said R6, R7 or R12 is directly bonded to a heteroatom and further provided that R6 is not H for groups (4) and (9), and R7 is not H for group (6); optionally, when R6 and R7 are bound to the same nitrogen, R6 and R7 together with the nitrogen to which they are bound, form a 5 to 7 membered heterocycloalkyl ring which optionally contains O, NR6, or S(O)t wherein t is