Patent ID: 6028201
Filing Date: 2000-02-22
Classification: C07D

Abstract:
A compound which inhibits farnesyl-protein transferase of the formula Ia: ##STR10## wherein: R.sup.1a and R.sup.2 are independently selected from: hydrogen or C.sub.1 -C.sub.6 alkyl;R.sup.1b 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, (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.5a and R.sup.5b are independently selected from:a) hydrogen, andb) 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) C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.2 -C.sub.6 alkynyl, C.sub.1 -C.sub.6 perfluoroalkyl, F, Cl, R.sup.8 O--, 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(R.sup.8).sub.2, or R.sup.9 OC(O)NR.sup.8 --, andc) C.sub.1 -C.sub.6 alkyl substituted by C.sub.1 -C.sub.6 perfluoroalkyl, R.sup.8 O--, R.sup.8 C(O)NR.sup.8 --, (R.sup.8).sub.2 N--C(NR.sup.8)--, R.sup.8 C(O)--, R.sup.8 OC(O)--, --N(R.sup.8).sub.2, or R.sup.9 OC(O)NR.sup.8 --;R.sup.7a is hydrogen or methyl;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 --, O, --N(R.sup.8)--, or S(O).sub.m ;V is selected from:a) heterocycle selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2-oxopiperidinyl, indolyl, quinolinyl, isoquinolinyl, and thienyl,b) aryl,c) C.sub.2 -C.sub.20 alkyl wherein from 0 to 4 carbon atoms are replaced with a heteroatom selected from O, S, and N, andd) C.sub.2 -C.sub.20 alkenyl, and; 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; and  or an optical isomer or pharmaceutically acceptable salt thereof.