| abstract |
The present invention relates to compounds of the general formula for inhibiting farnesyl protein transferase (FPT), wherein a, b, c and d are a nitrogen atom or an N + O group, and a, b, c and d are each other. independently <CR1 or <CR2; or each of a, b, c and d is independently <CR1 or <CR2; <- single or double bond; X is nitrogen or methine when a single bond is attached to C11 or carbon when a double bond is attached to C11; A and B are independently hydrogen; R9; -R9-C (O) -R9; R9-CO 2 R 9a; - (CH2) pR28; -C (O) N (R 9) 2; -C (O) NHR 9; -C (O) -NH-CH 2 -C (O) -NH2; -C (O) NHR26; - (CH2) pC (R9) -O-R9a; - (CH2) p (R9) 2; - (CH2) pC (O) R9; - (CH2) pC (O) R27a; - (CH2) pC (O) N (R9) 2; - (CH2) pC (O) NH (R9); - (CH2) pC (O) N (R26) 2; - (CH 2) p N (R9) -R9a; - (CH2) pN (R26) 2; - (CH 2) p NHC (O) R50; - (CH2) PNH (O) 2R50; - (CH 2) p N [C (O) R27a] 2; - (CH2) pNR51C (O) R27; - (CH2) p NR51C (O) NR27; - (CH2) pNR51C (O) N (R27a) 2; - (CH2) pNHSO2N (R51) 2; - (CH2) pNHCO2R50; - (CH2) pNC (O) NHR51; - (CH2) pCO2R51; -NHR9; -alkenyl-CO2R9a; alkenyl C (O) R 9a; -alkenyl-CO2R51; alkenyl C (O) -R 27; - (CH2) p-alkenyl-CO2-R51 ;-( CH2) pC = NOR51; - (CH 2) p-phthalimido; p is 0, 1, 2, 3 or 4; R1 and R2 are hydrogen, halogen, trifluoromethyl, -OR10, -COR10, -SR10, -S (O) tR15 (t is 0, 1 or 2), -N (R 10) 2, nitro, -OC (O) R 10, -CO 2 R 10, -OCO 2 R 15, cyano, -NR 10 COOR 15, -SR 15 C (O) OR 15, -SR 15 N (R 13) 2, wherein R 13 is hydrogen, -C ( O) OR15, (1-benzotriazolyl) oxy, (5-tetrazolyl) thio, optionally substituted alkynyl, alkenyl or alkyl; R3 and R4 are hydrogen, R1 or R2; R5, R6, R7 and R7 are hydrogen, trifluoromethyl, -COR10, optionally substituted alkyl or aryl, or R5 and R6 are oxo or thioxo; R8hydrogen or a group relates to the use of the compounds in pharmaceutical compositions, in the inhibition of abnormal cell growth, in the treatment of proliferative diseases and in the manufacture of medicaments. SHE |