Patent ID: 6462208
Filing Date: 2002-10-08
Classification: A61P,C07C,C07D,C07F

Abstract:
A taxane having the 2â€²R, 3â€²S configuration and corresponding to the structure whereinX1 is â€”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€”COX10, â€”COOX10, â€”COSX10, â€”CONX8X10, or â€”SO2X11; X6 is hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, hydroxy protecting group, or 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 alkyl, alkenyl, alkynyl, aryl, heteroaryl, or heterosubstituted alkyl, alkenyl, alkynyl, aryl or heteroaryl; X11 is alkyl, alkenyl, alkynyl, aryl, heteroaryl, â€”OX10, or â€”NX8X14; X14 is hydrogen, alkyl, alkenyl, alkynyl, aryl, or heteroaryl; 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 together with R2 forms an oxo; 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 formns an oxo, R5a is hydrogen, hydroxy, protected hydroxy, acyloxy, together with Rs forms an oxo, or together with R4 and the carbon atoms to which they are attached form an oxetane ring; R6 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 acyloxy; R7a is hydrogen; 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, protected hydroxy or together with R10 forms an oxo; R14 is hydrogen, alkyl, alkenyl, alkynyl, aryl, 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, and the taxane has a structure which differs from that of taxol or docetaxel with the respect to the C7 substituent and at least one other substituent.