| 摘要 |
Inhibition of farnesyl transferase, which is an enzyme involved in ras oncogene expression, is effected by compounds of the formulasand their enantiomers, diastereomers, and their pharmaceutically acceptable salts, including prodrugs and solvates thereof wherein:r, s and t are 0 or 1;m=0, 1, 2;p is 0, 1 or 2;X is selected from the group consisting of oxygen, hydrogen or R<1>, R<2>, R<3>;Y is selected from the group consisting of CHR<9>, SO2, CO, CO2, O, NR<10>, SO2NR<11 >and CONR<12>;R<6>, R<7>, R<9>, R<10>, R<11>, R<14>, R<15>, R<16>, R<17>, R<18>, R<19>, R<20>, R<21>, R<22>, R<23>, R<24>, R<25>, R<26>, R<27>, and R<28 >are selected from the group consisting of hydrogen, lower alkyl or substituted alkyl;R<4>, R<5 >are selected from the group consisting of hydrogen, halo, nitro, cyano and U-R<13>;R<12 >is selected from the group consisting of hydrogen, lower alkyl, aryl, substituted alkyl or aryl;U is selected from the group consisting of sulfur, oxygen, NR<14>, CO, SO, SO2, CO2, NR<15>CO2, NR<16>CONR<17>, NR<19>SO2, NR<19>SO2NR<20>, SO2NR<21>, NR<22>CO, CONR<23>, PO2R<24 >and PO3R<25 >or U is absent;R<1>, R<2>, R<3>, R<8 >and R<13 >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;R, S and T are selected from the group consisting of CH2, CO and CH(CH2)pQ wherein Q is NR<26>R<27 >or OR<28>;and A, B, C and D are carbon, oxygen, sulfur or nitrogen. with the proviso that R<13 >may be hydrogen except when U is SO, SO2, NR<15>CO2 or NR<18>SO2. |
