Inhibitors of farnesyl-protein transferase

A compound represented by formula I:

• ##STR8## or a pharmaceutically acceptable salt thereof, wherein:
• R.sup.1a, R.sup.1b and R.sup.2 are independently selected from the group consisting of:
• hydrogen, aryl, heterocyclyl, C.sub.3 -C.sub.10 cycloalkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.2 -C.sub.6 alkynyl, R.sup.8 O--, R.sup.9 S(O).sub.m --, (R.sup.8).sub.2 NC(O)--, R.sup.8 C(O)NR.sup.8 --, CN, NO.sub.2, (R.sup.8).sub.2 NC(NR.sup.8)--, R.sup.8 C(O)--, R.sup.8 OC(O)--, N.sub.3, --N(R.sup.8).sub.2, R.sup.9 OC(O)NR.sup.8 -- and C.sub.1 -C.sub.6 alkyl, unsubstituted or substituted by 1-3 groups selected from the group consisting of:
• halo, aryl, heterocyclyl, C.sub.3 -C.sub.10 cycloalkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.2 -C.sub.6 alkynyl, R.sup.8 O--, R.sup.9 S(O).sub.m --, R.sup.8 C(O)NR.sup.8 --, CN, (R.sup.8).sub.2 NC(NR.sup.8)--, R.sup.8 C(O)--, R.sup.8 OC(O)--, N.sub.3, --N(R.sup.8).sub.2 and R.sup.9 OC(O)NR.sup.8 --;
• R.sup.3 and R.sup.4 are independently selected from the group consisting of:
• H, F, Cl, Br, --NR.sup.8.sub.2, CF.sub.3, NO.sub.2, R.sup.8 O--, R.sup.9 S(O).sub.m --, (R.sup.8).sub.2 NC(O)--, R.sup.8 C(O)NH--, H.sub.2 NC(NH)--, R.sup.8 C(O)--, R.sup.8 OC(O)--, N.sub.3, CN, R.sup.9 OC(O)NR.sup.8 --, C.sub.1 -C.sub.20 alkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl;
• A.sup.3 is selected from:
• --NR.sup.5 S(O).sub.m -- or --S(O).sub.m NR.sup.5 --, with m equal to 0, 1 or 2, and R.sup.5 selected from the group consisting of:
• hydrogen, unsubstituted or substituted aryl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted C.sub.3 -C.sub.10 cycloalkyl, and C.sub.1 -C.sub.6 alkyl, unsubstituted or substituted with 1-3 members selected from the group consisting of:
• unsubstituted or substituted aryl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted C.sub.3 -C.sub.10 cycloalkyl, --N(R.sup.8).sub.2, --CF.sub.3, --NO.sub.2, (R.sup.8)O--, (R.sup.9)S(O).sub.m --, (R.sup.8)C(O)NH--, H.sub.2 NC(NH)--, (R.sup.8)C(O)--, (R.sup.8)OC(O)--, N.sub.3, CN and (R.sup.9)OC(O)NR.sup.8 --;
• R.sup.6 and R.sup.7 are independently selected from the group consisting of:
• hydrogen, aryl, heterocyclyl, C.sub.3 -C.sub.10 cycloalkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.2 -C.sub.6 alkynyl, C.sub.1-6 perfluoroalkyl, F, Cl, Br, R.sup.8 O--, R.sup.9 S(O).sub.m --, R.sup.8 C(O)NR.sup.8 --, CN, NO.sub.2, (R.sup.8).sub.2 NC(NR.sup.8)--, R.sup.8 C(O)--, R.sup.8 OC(O)--, N.sub.3, --N(R.sup.8).sub.2, R.sup.9 OC(O)NR.sup.8 -- and C.sub.1 -C.sub.6 alkyl unsubstituted or substituted by 1-3 groups selected from:
• aryl, heterocyclyl, C.sub.3 -C.sub.10 cycloalkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.2 -C.sub.6 alkynyl, perfluoroalkyl, F, Cl, Br, R.sup.8 O--, R.sup.9 S(O).sub.m --, R.sup.8 C(O)NR.sup.8 --, CN, (R.sup.8).sub.2 NC(NR.sup.8)--, R.sup.8 C(O)--, R.sup.8 OC(O)--, N.sub.3, --N(R.sup.8).sub.2 and R.sup.9 OC(O)NR.sup.8 --;
• each R.sup.8 is independently selected from hydrogen, C.sub.1 -C.sub.6 alkyl, aryl and aralkyl;
• each R.sup.9 is independently selected from C.sub.1 -C.sub.6 alkyl and aryl;
• A.sup.1 and A.sup.2 are independently selected from the group consisting of:
• a bond, --CH.dbd.CH--, --C.tbd.C--, --C(O)--, --C(O)NR.sup.8 --, --NR.sup.8 C(O)--, --O--, --N(R.sup.8)--, --S(O).sub.2 N(R.sup.8)--, --N(R.sup.8)S(O).sub.2 --, and S(O).sub.m ;
• X represents aryl or heteroaryl;
• V is selected from the group consisting of:
• hydrogen, heterocyclyl, aryl, C.sub.1 -C.sub.20 alkyl wherein from 0 to 4 carbon atoms are replaced with a heteroatom selected from O, S, and N, and C.sub.2 -C.sub.20 alkenyl, provided that V is not hydrogen if A.sup.1 is S(O).sub.m and V is not hydrogen if A.sup.1 is a bond, n is 0 and A.sup.2 is S(O).sub.m ;
• W represents heterocyclyl;
• each n and p independently represents 0, 1, 2, 3 or 4;
• r is 0 to 5, provided that r is 0 when V is hydrogen, and
• t is 1.