Inhibitors of farnesyl protein transferase

A method of inhibiting prenyl transferases which comprises administering to a mammal in need thereof an effective prenyl transferase inhibiting amount of a compound of formula I:

• wherein
• Y is selected from the group consisting of CHR12, SO2, SO3, CO, CO2, O, NR13, SO2NR14, CONR15, C(NCN), C(NCN)NR16, NR17CO, NR18SO2, CONR19NR20, SO2NR21NR22, S(O)(NR23), and S(NR24)(NR25), or without Y;
• Z is selected from the group consisting of S, SO, SO2, SO3, CO, CO2, O, NR13, SO2NR14, CONR15, NR26NR27, ONR28, NR29O, NR30SO2NR31, NR32SO2, NR33C(NCN), NR34C(NCN)NR35, NR36CO, NR37CONR38, NR39CO2, OCONR40, S(O)(NR41), and S(NR42)(NR43);
• R7 and R8 are selected from the group consisting of hydrogen, halo, nitro, cyano and U—R44;
• U is selected from the group consisting of S, O, NR45, CO, SO, SO2, CO2, NR46CO2, NR47CONR48, NR49SO2, NR50SO2NR51, SO2NR52, NR53CO, CONR54, PO2R55 and PO3R56 or without U;
• R9, R10, R12, R13, R14, R15, R16, R17, R18, R19, R20, R21, R22, R23, R24, R25, R26, R27, R28, R29, R30, R31, R32, R33, R34, R35, R36, R37, R38, R39, R40, R41, R42, R43, R44, R45, R46, R47, R48, R49, R50, R51, R52, R53, R54, R55, R56, R57, R58, and R59 are selected from the group consisting of hydrogen, lower alkyl, aryl, heterocyclo, substituted alkyl and aryl;
• R11 and R44 are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, cycloalkyl, aryl, substituted aryl, heterocyclo, and substituted heterocyclo;
• R1, R2, R3, R4, R5 and R6 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, cyano, alkoxycarbonyl, carboxy, carbamyl, and substituted carbamyl wherein substituents on the nitrogen of the substituted carbamyl are selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, aralkyl, substituted aryl, heterocyclo, and substituted heterocyclo;
• any two of R1, R2, R3, R4, R5 and R6 can join to form a cycloalkyl group;
• any two of R1, R2, R3, R4, R5 and R6 together can be oxo, except when the carbon atom bearing the substituent is part of a double bond;
• R, S and T are selected from the group consisting of CH2 and CH(CH2)pQ wherein Q is NR57R58, OR59, or CN;
• wherein p is 0, 1 or 2;
• and
• A, B, C and D are carbon;
• its enantiomer, diastereomer, pharmaceutically acceptable salt or solvate thereof;
• with the provisos that:
• R11 may be hydrogen except when Z is SO, or when Z is O, NR13 or S and the carbon to which it is attached is part of a double bond or when Y is SO2, CO2, NR18SO2, S(O)(NR23), or S(NR24)(NR25);
• and
• R44 may be hydrogen except when U is SO, SO2, NR46CO2 or NR49SO2.