Patent ID: 6794523
Filing Date: 2004-09-21
Classification: A61P,C07C,C07D,C07F

Abstract:
A taxane derivative having the formula whereinX1 is OX6, â€”SX7, or â€”NX8X9; X2 is hydrogen, alkyl, alkenyl, alkynyl, aryl, or heteroaryl; X3 and X4 are independently hydrogen, alkyl, alkenyl, alkynyl, aryl or heteroaryl; X5 is â€”COOX10; X6 is hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, hydroxy protecting group, or a functional group which increases the water solubility of the taxane derivative; X7 is alkyl, alkenyl, alkynyl, aryl, heteroaryl, or sulfhydryl protecting group; X8 is hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, or heterosubstituted alkyl, alkenyl, alkynyl, aryl or heteroaryl; X9 is an amino protecting group; X10 is t-butyl; R1 is hydrogen, hydroxy, protected hydroxy, or together with R14 forms a carbonate; R2 is hydrogen, hydroxy, â€”OCOR31 or together with R2a forms an oxo; R2a is hydrogen or taken together with R2 forms an oxo or; R4 is hydrogen, together with R4a forms an oxo, oxirane or methylene, or together with R5a and the carbon atoms to which they are attached form an oxetane ring; R4a is hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cyano, hydroxy, â€”OCOR30, or together with R4 forms an oxo, oxirane or methylene; R5 is hydrogen or together with R5a forms an oxo, R5a is hydrogen, hydroxy, protected hydroxy, acyloxy, together with R5 forms an oxo, or together with R4 and the carbon atoms to which they are attached form an oxetane ring; R5 is hydrogen, alkyl, alkenyl, alkynyl, aryl, or heteroaryl, hydroxy, protected hydroxy or together with R6a forms an oxo; R6a is hydrogen, alkyl, alkenyl, alkynyl, aryl, or heteroaryl, hydroxy, protected hydroxy or together with R6 forms an oxo; R7 is hydrogen or together with R7a forms an oxo, R7a is hydrogen, halogen, protected hydroxy, â€”OR28, or together with R7 forms an oxo; R9 is hydrogen or together with R9a forms an oxo, R9a is hydrogen, hydroxy, protected hydroxy, acyloxy, or together with R9 forms an oxo; R10 is hydrogen or together with R10a forms an oxo, R10a is hydrogen, â€”OCOR29, hydroxy, or protected hydroxy, or together with R10 forms an oxo; R14 is hydrogen, alkyl, alkenyl, alkynyl, aryl, or heteroaryl, hydroxy, protected hydroxy or together with R1 forms a carbonate; R14a is hydrogen, alkyl, alkenyl, alkynyl, aryl, or heteroaryl; R28 is hydrogen, acyl, hydroxy protecting group or a functional group which increases the solubility of the taxane derivative; R29, R30, and R31 are independently hydrogen, alkyl, alkenyl, alkynyl, monocyclic aryl or monocyclic heteroaryl, provided, however, at least one of R1-R31 has a value such that the structure of the taxane is different from that of docetaxel.