TRICYCLIC PIPERDINYL DERIVATIVES USE AS FARNESYL PROTEIN TRANSFERASE INHIBITORS

摘要

Novel tricyclic compounds of formula (1.0) or a pharmaceutically acceptable salt or solvate thereof, wherein: one of a, b, c, and d represents N or NR9, wherein R9 is O-, -CH3 or -(CH2)nCO2H wherein n is 1 to 3, and the remaining a, b, c and d groups represent CR1 or CR2; or each of a, b, c and d is independently selected from CR1 or CR2; each R1 and each R2 is independently selected from H, halo, -CR3, -OR10, -COR10, -SR10, -S(O)tR11 (wherein t is 0, 1 or 2), -SCN, -N(R10)2, -NR10R11, -NO2, -OC(O)R10, -CO2R10, -OCO2R11, -CN, -NHC(O)R10, -NHSO2R10, -CONHR10, -CONHCH2CH2OH, -NR10COOR11, -SR11C(O)OR11, -SR11N(R75)2; n is 0 (zero), 1, 2, 3, 4, 5 or 6; T is -CO-; -SO-; -SO2-; or -CR30R31-; Z represents alkyl, aryl, aralkyl, heteroalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl, heterocycloalkylalkyl, -OR40, -SR40, -CR40R42, -NR40R42, formulae (i), (ii), (iii), (iv), (v) and (vi). Pharmaceutical compositions are disclosed which are inhibitors of the enzyme, farnesyl protein transferase. Also disclosed is a method of inhibiting Ras function and therefore inhibiting the abnormal growth of cells. The method comprises administering the novel tricyclic compound to a biological system. In particular, the method inhibits the abnormal growth of cells in a mammal such as a human.