| 摘要 |
A taxol derivative of formula I (see fig I) or a pharmaceutically acceptable salt thereof, in which R j is -COR2 in which R2 is t-butyloxy, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, or phenyl, optionally substituted with one to three same or different C1-6 alkyl, C1-6 alkoxy, halogen or -CF3 groups; R y is C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, or a radical of the formula -W-R x in which W is a bond, C2-6 alkenediyl, or -(CH2)t -, in which t is one to six; and R x is naphthyl, furyl, thienyl or phenyl, and furthermore R x can be optionally substituted with one to three same or different C1-6 alkyl, C1-6 alkoxy, halogen or -CF3 groups; R w is hydrogen, hydroxy, acetyloxy, -OC(=O)OY or -OZ; R1 is hydrogen, hydroxy, -OC(=O)OY or -OZ; R2 is hydroxy, -OC(=O)OY, -OC(=O)R or -OZ, with the proviso at least one of R1, R2 or R w is -OC(=O)OY or -OZ; R is C1-6 alkyl; Z is of the formula <IMGS> wherein R3 and R4 are independently hydrogen or C1-6 alkyl, or R3 and R4 taken together with the carbon atom to which they are attached form C3-6 cycloalkylidene; R5 is -OC(=O)R, -OP=O(OH)2 or -CH2OP=O(OH)2; R6, R7, R8 and R9 are independently halogen, C1-6 alkyl, C1-6 alkoxy or hydrogen; or one of R6, R7, R8 and R9 is -OC(=O)R, -OP=O(OH)2 or hydroxy, and the others are independently halogen, C1-6 alkyl, C1-6 alkoxy or hydrogen; but when R5 is -OC(=O)R, one of R6, R7, R8 or R9 must be -OP=O(OH)2; Q is -(CH2)q-, optionally substituted with one to six same or different C1-6 alkyl or C3-6 cycloalkyl, or a carbon atom of said -(CH2)q- group can also be a part of C3-6 cycloalkylidene; q is 2 to 6; n is 0, and m is 1 or 0 when R5 is -CH2OP=O(OH)2; n is 1 or 0, and m is 1 when R5 is -OC(=O)R or -OF=O(OH)2; Y is C1-6 alkyl (optionally substituted with -OP=O(OH)2 or one to six same or different halogen atoms), C3-6 cycloalkyl, C2-6 alkenyl, or a radical of the formula in which D is a bond or -(CH2)t-, optionally substituted with one to six same or different C1-6 alkyl; and R a, R b and R c are independently hydrogen, amino, C1-6 alkylamino, di-C1-6 alkylamino, halogen, C1-6 alkyl, or C1-6 alkoxy; and with the further proviso that R2 cannot be -OP=O(OH)2; and Y cannot be -CH2CCl3.
|
