C10 OXO and hydrido taxane derivatives and pharmaceutical compositions containing them

A taxane having the 2′R, 3′S configuration and corresponding to the structure

• wherein
• X1 is —OX6, —SX7, or —NX8X9;
• X2 is hydrogen, alkyl, alkenyl, alkynyl, aryl, or heteroaryl;
• X3 and X4 are independently hydrogen, alkyl, alkenyl, alkynyl, aryl, or heteroaryl;
• X5 is —COX10, —COOX10, —COSX10, —CONX8X10, or —SO2X11;
• X6 is hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, or hydroxy protecting group;
• X7 is alkyl, alkenyl, alkynyl, aryl, heteroaryl, or sulfhydryl protecting group;
• X8 is hydrogen, alkyl, alkenyl, alkynyl, aryl, or heteroaryl;
• X9 is an amino protecting group;
• X10 is alkyl, alkenyl, alkynyl, aryl, or heteroaryl;
• X11 is alkyl, alkenyl, alkynyl, aryl, heteroaryl, —OX10, or —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, —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, —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;
• 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 together with R7a forms an oxo;
• R7a is hydrogen, halogen, —OR28, or together with R7 forms an oxo;
• R9 is hydrogen or together with R9 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 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;
• 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 each of paclitaxel and docetaxel with respect to the C10 substituent and at least one other substituent.