Patent NZ-334452-A (NZ)
Title: Tricyclic piperidinyl compounds useful as inhibitors of farnesyl-protein transferase (FTase)
Inventor: COOPER ALAN B
IPC: A61K31/4545
Filed: 1997-09-11
Abstract: A compound of  formula 1 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 are independently selected from CR1 or CR2, each R1 and each R2 is independently selected from H, halo, CF3, 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, wherein each R75 is independently selected from H and C(O)OR11, benzotriazol-1-yloxy, tetrazol-5-ylthio, or substituted tetrazol-5ylthio, alkynyl, alkenyl or alkyl, said alkyl or alkenyl group optionally being substituted with halo, OR10 or CO2R10, R3 and R4 are the same or different and each independently represents H, any of the substituents of R1 and R2, or R3 and R4 taken together represent a saturated or unsaturated C5-C7 fused ring to the benzene ring (Ring III), R5, R6, R7 and R8 each independently represents H, CF3, COR10, alkyl or aryl, said alkyl or aryl optionally being substituted with OR10, SR10, S(O)tR11, NR10COOR11, N(R10)2, NO2, COR10, OCOR10, OCO2R11, OCO2R10, OPO3R1 , or R5 is combined with R6 to represent O or S, R7 is combined with R8 to represent O or S, R10 represents H, alkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, aryl, aralkyl or NR40R42 wherein R40 and R42 independently represent H, aryl, alkyl, aralkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroalkyl, cycloalkyl, cycloalkylalkyl, alkenyl and alkynyl, R11 represents alkyl or aryl, the dotted line between carbon atoms 5 and 6 represents an optional double bond, such that when a double bond is present, A and B independently represent NO2, R10, halo, OR11, OCO2R11 or OC(O)R10, and when no double bond is present between carbon atoms 5 and 6, A and B each independently represent H2, (OR11)2, H and halo, dihalo, alkyl and H, (alkyl)2, H and OC(O)R10, H and OR10, oxy, aryl and H, =NOR10 or O(CH2)pO wherein p is 2, 3 or 4, n is 0 (zero), 1, 2, 3, 4, 5 or 6, T is CO, SO, SO2-, or CR30R31 wherein R30 and R31 independently represent H, alkyl, aryl, aralkyl, heteroalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl or heterocycloalkylalkyl; and Z represents alkyl, aryl, aralkyl, heteroalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl, heterocycloalkylalkyl, OR40, SR40, CR40R42, NR40R42, or a group of formula 2-7, wherein n, R40 and R42 are defined hereinbefore, m is 2, 3 4, 5, 6, 7 or 8, qis0(zero), 1 or 2; and R14 represents H, C1-6 alkyl, aralkyl, heteroaryl, acyl, carboxamido, carboxamidoalkyl, cyano, alkoxycarbonyl, aralkyloxycarbonyl, D and L amino acids covalently bonded through the carboxyl group, imido, imidamido, sulfamoyl, sulfonyl, dialkylphosphinyl, N-glycosyl, or a group of formula 8-16, C(NHCH3)=CHNO2, with the proviso that when T is SO, Z is not NR40R42. Also described is the use of the above mentioned farnesyl-protein transferase inhibitors in the manufacture of a medicament for inhibiting abnormal cell growth.