Patent ID: 6066738
Filing Date: 2000-05-23
Classification: A61P,C07D

Abstract:
A compound which inhibits farnesyl-protein transferase of the formula I: ##STR9## wherein: R.sup.1a, and R.sup.1b are independently selected from:a) hydrogen,b) aryl, heterocycle, 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, NO.sub.2, (R.sup.8).sub.2 N--C (NR.sup.8)--, R.sup.8 C(O)--, R.sup.8 OC(O)--, N.sub.3, --N(R.sup.8).sub.2, or R.sup.9 OC(O)NR.sup.8 --,c) C.sub.1 -C.sub.6 alkyl unsubstituted or substituted by aryl, heterocyclic, 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 N--C(NR.sup.8)--, R.sup.8 C(O)--, R.sup.8 OC(O)--, N.sub.3, --N(R.sup.8).sub.2, or R.sup.9 OC(O)--NR.sub.8 --;R.sup.2 is independently selected from:a) hydrogen,b) aryl, heterocycle, cycloalkyl, R.sup.8 O--, --N(R.sup.8).sub.2 or C.sub.2 -C.sub.6 alkenyl,c) C.sub.1 -C.sub.6 alkyl unsubstituted or substituted by aryl, heterocycle, cycloalkyl, alkenyl, R.sup.8 O--, or --N(R.sup.8).sub.2 ;R.sup.3 and R.sup.4 are independently selected from H, F, Cl, Br, 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 N--C(NH)--, (R.sup.8)C(O)--, (R.sup.8)OC(O)--, N.sub.3, CN, CF.sub.3 (CH.sub.2).sub.n O--, (R.sup.9)OC(O)NR.sup.8 --, C.sub.1 -C.sub.20 alkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocycle;R.sup.5 is selected from:a) hydrogen,b) unsubstituted or substituted aryl,c) unsubstituted or substituted heterocyclic,d) unsubstituted or substituted C.sub.3 -C.sub.10 cycloalkyl, ande) C.sub.1 -C.sub.6 alkyl substituted with hydrogen or a group selected from unsubstituted or substituted aryl, unsubstituted or substituted heterocyclic, 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 N--C(NH)--, (R.sup.8)C(O)--, (R.sup.8)OC(O)--, N.sub.3, CN(R.sup.9)OC(O)NR.sup.8 --;R.sup.6 is independently selected from:a) hydrogen,b) aryl, heterocycle, 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, NO.sub.2, R.sup.8.sub.2 N--C(NR.sup.8)--, R.sup.8 C(O)--, R.sup.8 OC(O)--, N.sub.3, --N(R.sup.8).sub.2, or R.sup.9 OC(O)NR.sup.8 --, andc) C.sub.1 -C.sub.6 alkyl unsubstituted or substituted by aryl, heterocycle, 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)NH--, CN, H.sub.2 N--C(NH)--, R.sup.8 C(O)--, R.sup.8 OC(O)--, N.sub.3, --N(R.sup.8).sub.2, or R.sup.8 OC(O)NH--;R.sup.7 is selected from:a) hydrogen,b) 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, NO.sub.2, (R.sup.8).sub.2 N--C--(NR.sup.8)--, R.sup.8 C(O)--, R.sup.8 OC(O)--, N.sub.3, --N(R.sup.8).sub.2, or R.sup.9 OC(O)NR.sup.8 --, andc) C.sub.1 -C.sub.6 alkyl unsubstituted or substituted by 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 N--C(NR.sup.8)--, R.sup.8 C(O)--, R.sup.8 OC(O)--, N.sub.3, --N(R.sup.8).sub.2, or R.sup.9 OC(O)NR.sup.8 --;R.sup.8 is independently selected from hydrogen, C.sub.1 -C.sub.6 alkyl, benzyl and aryl;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: 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 --, or S(O).sub.m ;A.sup.3 is selected from: --NR.sup.5 C(O)-- or --C(O)NH--;V is selected from:a) heterocycle, andb) aryl,W is a heterocycle;Y is aryl or heteroaryl;m is 0, 1 or 2;n is 0, 1, 2, 3 or 4;p is 0, 1, 2, 3 or 4;r is 0 to 5; andt is 1;or an optical isomer or pharmaceutically acceptable salt thereof.