Histidine and homohistidine derivatives as inhibitors of protein farnesyltransferase

An inhibitor of protein farnesyltransferase which is a histidine or homohistidine derivative of the Formula I, ##STR9## wherein:

• n=1 or 2;
• A=COR.sup.2, CO.sub.2 R.sup.2, CONHR.sup.2, CSR.sup.2, C(S)OR.sup.2, C(S)NHR.sup.2, or SO.sub.2 R.sup.2 with R.sup.2 as defined below;
• R=independently H or Me;
• R.sup.2 =alkyl, (CH.sub.2).sub.m -cycloalkyl, (CH.sub.2).sub.m -aryl, or (CH.sub.2).sub.m -heteroaryl with m=0, 1, 2, or 3;
• R.sup.3 and R.sup.4 =independently (CH.sub.2).sub.x -R.sup.7, with x=2-5 and R.sup.7 as defined below, ##STR10## or (CH.sub.2).sub.n CONH-R.sup.6 with y=1-5 and n as defined above and with R.sup.5 and R.sup.6 as defined below, or R.sup.3 and R.sup.4 are connected together to form a ring of the following type:
• ##STR11## with R.sup.5 and R.sup.6 as defined below;
• R.sup.5 =R.sup.2, OR.sup.2, or SR.sup.2 with R.sup.2 as defined above;
• R.sup.6 =(CH.sub.2).sub.n R.sup.5, (CH.sub.2).sub.n CO.sub.2 R.sup.2, (CH.sub.2).sub.n CONHR.sup.2, (CH.sub.2).sub.n CONH(CH.sub.2).sub.n+1 R.sup.5, or CH(COR.sup.8)(CH.sub.2).sub.n R.sup.5, with n, R.sup.2, and R.sup.5 as defined above and R.sup.8 as defined below;
• R.sup.7 =(CH.sub.2).sub.m -cycloalkyl, (CH.sub.2).sub.m -aryl, (CH.sub.2).sub.m -heteroaryl, O(CH.sub.2).sub.m -cycloalkyl, O(CH.sub.2).sub.m -aryl, or O(CH.sub.2).sub.m -heteroaryl with m=0, 1, 2, or 3;
• R.sup.8 =OH, O-alkyl, NH.sub.2, or NH-alkyl;
• and
• X=H, Me, (CH.sub.2).sub.n CO.sub.2 R.sup.9, or (CH.sub.2).sub.n P(O)(OR.sup.9).sub.2, with R.sup.9 =H or alkyl;
• or a pharmaceutically acceptable salt thereof.