Patent ID: 7414073

Claim:
A cytotoxic agent composed of one or more compounds of formula (I-1) covalently bonded to a cell-binding agent through a link from the oxygen atom at the C-7 position of formula (I-1): wherein: R 1 is H, an electron withdrawing group, or an electron donating group; R 1 ′ and R 1 ″ are the same or different, and are H, an electron withdrawing group, or an electron donating group; R 2 is H, or together with the oxygen atom at the C-10 position, a heterocyclic or aryl ether group, a heterocyclic or aryl ester group, a heterocyclic or aryl carbamate group, a linear, branched or cyclic alkyl ester group having from 1 to 10 carbon atoms in the alkyl, a linear, branched or cyclic alkenyl ester group having from 2 to 10 carbon atoms in the alkenyl, a linear, branched or cyclic alkyl ether group having from 1 to 10 carbon atoms, a linear, branched or cyclic alkenyl ether group having from 2 to 10 carbon atoms, a carbamate group of the formula —OCOX, wherein X is a nitrogen-containing heterocyclic group, or a carbamate of the formula —OCONR 10 R 11 , wherein R 10 and R 11 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; R 3 is alkenyl having from 2 to 10 carbon atoms, cycloalkenyl having from 3 to 10 carbon atoms or heterocyclic; R 4 is alkyl having from 1 to 10 carbon atoms, alkenyl having from 2 to 10 carbon atoms, cycloalkyl or cycloalkenyl having from 3 to 10 carbon atoms, aryl, heterocyclic, —OC(CH 3 ) 3 , or together with the —CONH— group at the C-3′ position, a carbamate formed from any of said alkyl having from 1 to 10 carbon atoms, alkenyl having from 2 to 10 carbon atoms, cycloalkyl or cycloalkenyl having from 3 to 10 carbon atoms, aryl or heterocyclic and an oxygen atom; and R 6 is H, or together with the oxygen atom at the C-2′ position, a heterocyclic or aryl ether, a heterocyclic or aryl ester, a heterocyclic or aryl carbamate, a linear, branched or cyclic alkyl ester group having from 1 to 10 carbon atoms in the alkyl, a linear, branched or cyclic alkenyl ester group having from 2 to 10 carbon atoms in the alkenyl, a linear, branched, or cyclic alkyl ether group having from 1 to 10 carbon atoms, a linear, branched, or cyclic alkenyl ether group having from 2 to 10 carbon atoms, a carbamate group of the formula —OCOX, wherein X is a nitrogen-containing heterocyclic group, or a carbamate of the formula —OCONR 10 R 11 , wherein R 10 and R 11 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 provided that when R 3 is —CH═C(CH 3 ) 2 , R 4 is not an aryl or —OC(CH 3 ) 3 , and wherein the cell-binding agent is selected from the group consisting of antibodies and fragments thereof, interferons, lymphokines, hormones, vitamins, growth factors, colony-stimulating factors and transferrin.