Cytotoxic agents containing novel potent taxanes and their therapeutic use

A compound represented by formula (I):

• 3
• wherein:
• R2 is a linking group;
• R1 is H, an electron withdrawing group or an electron donating group;
• R1′ and R1″ are the same or different and are H, an electron withdrawing group, or an electron donating group;
• R3 and R4 are the same or different and are alkyl or alkenyl having from 1 to 10 carbon atoms, cycloalkyl or cycloalkenyl having from 3 to 10 carbon atoms, aryl, or heterocycle and R4 additionally is —OC(CH3)3 or a carbamate formed from any of said alkyl, alkenyl, cycloalkyl, cycloalkenyl having from 3 to 10 carbon atoms, aryl, or heterocycle;
• R5 and R6 are the same or different and are H, a heterocyclic or aryl ether, ester or carbamate, or a linear, branched, or cyclic alkyl or alkenyl ester or ether having from from 1 to 10 carbon atoms or a carbamate of the formula —COX, wherein X is a nitrogen-containing heterocycle, or a carbamate of the formula —CONR10R11, wherein R10 and R11 are the same or different and are H, linear, branched, or cyclic alkyl having from 1 to 10 carbon atoms or simple or substituted aryl having from 1 to 10 carbon atoms.

The compound represented by Formula (I),

• 4
• wherein:
• R5 is a linking group;
• R1 is H, an electron withdrawing group or an electron donating group;
• R1′ and R1″ are the same or different and are H, an electron withdrawing group, or an electron donating group;
• R3 and R4 are the same or different and are alkyl or alkenyl having from 1 to 10 carbon atoms, cycloalkyl or cycloalkenyl having from 3 to 10 carbon atoms, aryl, or heterocycle and R4 additionally is —OC(CH3)3 or a carbamate formed from any of said alkyl, alkenyl, cycloalkyl, cycloalkenyl having from 3 to 10 carbon atoms, aryl, or heterocycle;
• R2 and R6 are the same or different and are H, a heterocyclic or aryl ether, ester or carbamate, or, a linear, branched, or cyclic alkyl or alkenyl ester or ether having from from 1 to 10 carbon atoms or a carbamate of the formula —COX, wherein X is a nitrogen-containing heterocycle, or a carbamate of the formula —CONR10R11, wherein R10 and R11, are the same or different and are H, linear, branched, or cyclic alkyl having from 1 to 10 atoms or simple or substituted aryl having from 1 to 10 carbon atoms.

A compound represented by formula (I):

• 5
• wherein:
• R6 is a linking group;
• R1 is H, an electron withdrawing group or an electron donating group;
• R1′ and R1″ are the same or different and are H, an electron withdrawing group, or an electron donating group;
• R3 and R4 are the same or different and are alkyl or alkenyl having from 1 to 10 carbon atoms, cycloalkyl or cycloalkenyl having from 3 to 10 carbon atoms, aryl, or heterocycle and R4 additionally is —OC(CH3)3 or a carbamate formed from any of said alkyl, alkenyl, cycloalkyl, cycloalkenyl, having from 3 to 10 carbon atoms, aryl, or heterocycle;
• R2 and R5 are the same or different and are H, a heterocyclic or aryl ether, ester or carbamate, or, a linear, branched, or cyclic alkyl or alkenyl ester or ether having from from 1 to 10 carbon atoms or a carbamate of the formula —COX, wherein X is a nitrogen-containing heterocycle such as piperidino, morpholino, piperazino, N-methylpiperazino, or a carbamate of the formula —CONR10R11, wherein R10 and R11 are the same or different and are H, linear, branched, or cyclic alkyl having from 1 to 10 atoms or simple or substituted aryl having from 1 to 10 carbon atoms;

A compound represented by formula (I):

• 6
• wherein:
• R3 is a linking group;
• R1 is H, an electron withdrawing group or an electron donating group;
• R1′ and R141 are the same or different and are H, an electron withdrawing group, or an electron donating group;
• R4 is alkyl or alkenyl having from 1 to 10 carbon atoms, cycloalkyl or cycloalkenyl having from 3 to 10 carbon atoms, aryl, or heterocycle and R4 additionally is —OC(CH3)3 or a carbamate formed from any of said alkyl, alkenyl, cycloalkyl, cycloalkenyl, having from 3 to 10 carbon atoms, aryl, or heterocycle;
• R2, R5 and R6 are the same or different and are H, a heterocyclic or aryl ether, ester or carbamate, or, a linear, branched, or cyclic alkyl or alkenyl ester or ether having from from 1 to 10 carbon atoms or a carbamate of the formula —COX, wherein X is a nitrogen-containing heterocycle such as piperidino, morpholino, piperazino, N-methylpiperazino, or a carbamate of the formula —CONR10R11, wherein R10 and R11 are the same or different and are H, linear, branched, or cyclic alkyl having from 1 to 10 atoms or simple or substituted aryl having from 1 to 10 carbon atoms.

A compound represented by formula (I):

• 7
• wherein:
• R4 is a linking group;
• R1 is H, an electron withdrawing group or an electron donating group;
• R1′ and R1″ are the same or different and are H, an electron withdrawing group, or an electron donating group;
• R3 is alkyl or alkenyl having from 1 to 10 carbon atoms, cycloalkyl or cycloalkenyl having from 3 to 10 carbon atoms, aryl, or heterocycle and R4 additionally is —OC(CH3)3 or a carbamate formed from any of said alkyl, alkenyl, cycloalkyl, cycloalkenyl, having from 3 to 10 carbon atoms, aryl, or heterocycle;
• R2, R5 and R6 are the same or different and are H, a heterocyclic or aryl ether, ester or carbamate, or, a linear, branched, or cyclic alkyl or alkenyl ester or ether having from from 1 to 10 carbon atoms or a carbamate of the formula —COX, wherein X is a nitrogen-containing heterocycle such as piperidino, morpholino, piperazino, N-methylpiperazino, or a carbamate of the formula —CONR10R11, wherein R10 and R11 are the same or different and are H, linear, branched, or cyclic alkyl having from 1 to 10 atoms or simple or substituted aryl having from 1 to 10 carbon atoms;