Cytotoxic agents comprising taxanes and their therapeutic use
AssigneeImmunoGen, Inc.
InventorsRavi V. J. Chari, Walter A. Blättler
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Abstract
A cytotoxic agent comprising one or more taxanes linked to a cell binding agent. A therapeutic composition for killing selected cell populations comprising: (A) a cytotoxic amount of one or more taxanes covalently bonded to a cell binding agent through a linking group, and (B) a pharmaceutically acceptable carrier, diluent or excipient. A method for killing selected cell populations comprising contacting target cells or tissue containing target cells with an effective amount of a cytotoxic agent comprising one or more taxanes linked to a cell binding agent. Novel sulfur-containing taxanes.
Claims17
A compound represented by formula (I):
- wherein:
- R1″ is H,
- R1 and R1′ are the same or different and are F, NO2, CN, Cl, CHF2, CF3, —NR7R8 or —OR9 wherein R7 and R8 are the same or different and are linear alkyl having 1 to 10 carbon atoms, branched or cyclic alkyl having 3 to 10 carbon atoms, or simple or substituted phenyl or naphthyl and R9 is linear alkyl having 1 to 10 carbon atoms, or branched or cyclic alkyl having 3 to 10 carbon atoms;
- R2 is —CONR10R11, wherein R10 and R11 are the same or different and are H, linear alkyl having 1 to 10 carbon atoms, branched or cyclic alkyl having 3 to 10 carbon atoms, or aryl;
- R3 is aryl, linear alkyl having 1 to 10 carbon atoms, or branched or cyclic alkyl having 3 to 10 carbon atoms;
- R4 is —OC(CH3)3 or phenyl;
- R5 is —(CH2)nSZ, —CO(CH2)nSZ, —(CH2)nCH(CH3)SZ, —CO(CH2)nCH(CH3)SZ, —(CH2)nC(CH3)2SZ, —CO(CH2)nC(CH3)2SZ, —CONR12(CH2)nSZ, —CONR12(CH2)nCH(CH3)SZ, —CONR12(CH2)nC(CH3)2SZ, —CO-morpholino-XSZ, —CO-piperidino-XSZ, —CO-piperazino-XSZ, or —CO—N-methylpiperazino-XSZ, wherein
- Z is H or SR, wherein R and R12 are the same or different and are linear alkyl having 1 to 10 carbon atoms, branched or cyclic alkyl having 3 to 10 carbon atoms, or simple or substituted phenyl, naphthyl or heterocyclic, and R12 in addition can be H,
- X is linear alkyl having 1 to 10 carbon atoms or branched alkyl having 3 to 10 carbon atoms, and
- n is an integer of ito 10;
- and
- R6 is H.
A cytotoxic composition comprising one or more taxanes convalently bonded to a cell binding agent through a linking group, wherein at least one of said taxanes is a compound represented by formula (I):
- wherein:
- R1″ is H,
- R1 and R1′ are the same or different and are F, NO2, CN, Cl, CHF2, CF3, —NR7R8 or —OR9 wherein R7 and R8 are the same or different and are linear alkyl having 1 to 10 carbon atoms, branched or cyclic alkyl having 3 to 10 carbon atoms, or simple or substituted phenyl or napthyl and R9 is linear alkyl having 1 to 10 carbon atoms, or branched or cyclic alkyl having 3 to 10 carbon atoms;
- R2 —CONR10R11, wherein R10 and R11 are the same or different and are H, linear alkyl having 1 to 10 carbon atoms, branched or cyclic alkyl having 3 to 10 carbon atoms, or aryl;
- R3 is aryl, linear alkyl having 1 to 10 carbon atoms, or branched or cyclic alkyl having 3 to 10 carbon atoms;
- R4 is —OC(CH3)3 or phenyl;
- R5 is —(CH3)nSZ, —CO(CH2)nSZ, —(CH2)nCH(CH3)SZ, —CO(CH2)nCH(CH3)SZ, —(CH2)nC(CH3)2SZ, —CO(CH2)nC(CH3)2SZ, —CONR12(CH2)nCH(CH3)SZ, —CONR12(CH2)nC(CH3)2SZ, —CO-morpholino-XSZ, —CO-piperidino-XSZ, or —CO—N-methylpiperazino-XSZ wherein:
- Z is H or SR, wherein R and R12 are the same or different and are linear alkyl having 1 to 10 carbon atoms, branched or cyclic alkyl having from 3 to 10 carbon atoms, or simple or substituted phenyl, naphthyl or heterocyclic, and R12 in addition can be H,
- X is linear alkyl having 1 to 10 carbon atoms or branched alkyl having 3 to 10 carbon atoms, and
- n is an integer of 1 to 10;
- and
- R6 is H.
Dependencies are inferred from the claim text.