| abstract |
Inhibition of farnesyl transferase, which is an enzyme involved in ras ocogene expression, is effected by compounds of the formulastheir enantiomers, diastereomers, and pharmaceutically acceptable salts, prodrugs and solvates thereof inhibit farnesyl protein transferase which is an enzyme involved in ras oncogene expression. In formulas I-IV and throughout their specification, the above symbols are defined as follows:m, n, r, s and t are 0 or 1;p is 0, 1 or 2;V, W and X are selected from the group consisting of oxygen, hydrogen, R1, R2 or R3;Z and Y are selected from the group consisting of CHR9, SO2, SO3, CO, CO2, O, NR10, So2NR11, CONR12,or Z may be absent;R6, R7, R9, R10, R11, R12 R13, R14, R15, R16, R17, R18, R19, R20, R21, R22, R24, R25, R26, R27, R28, R29, R30, R31, R32,R33, R34, R35, R36, R37, and R38 are selected from the group consisting of hydrogen, lower alkyl, substituted alkyl, aryl or substituted aryl;R4, R5 are selected from the group consisting of hydrogen, halo, nitro, cyano and U-R23;U is selected from the group consisting of sulfur, oxygen, NR24, CO, SO, SO2, CO2, NR25CO2, NR26CONR27, NR28SO2, NR29SO2NR30, SO2NR31, NR32CO, CONR33, PO2R34 and PO3R35 or U is absent;R1, R2, and R3 are selected from the group consisting of hydrogen, alkyl, alkoxycarbonyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, cycloalkyl, aryl, substituted aryl, heterocyclo, substituted heterocyclo, cyano, carboxy, carbamyl (e.g. CONH2) or substituted carbamyl further selected from CONH alkyl, CONH aryl, CONH aralkyl or cases where there are two substituents on the nitrogen selected from alkyl, aryl or aralkyl;R8 and R23 are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, cycloalkyl, aryl, substituted aryl, heterocyclo, substituted heterocyclo;Any two of R1, R2, and R3 can be joined to form a cycloalkyl group; R, S and T are selected from the group consisting of CH2, CO and CH(CH2)pQ wherein Q is NR36R37, OR38, or CN; andA, B, C and D are carbon, oxygen, sulfur or nitrogen.with the provisos that1. When m is zero then V and W are not both oxygen or2 W and X together can be oxygen only if Z is either absent, O, NR10,in formulas I and II, and V and X together can be oxygen only if Y is O, NR10,in formulas III and IV or3. R23 may be hydrogen except when U is SO, SO2, NR25CO2 or NR28SO2, or4. R8 may be hydrogen except when Z is SO2, CO2, or |