CA2388063A1 - Cytotoxic agents comprising taxanes and their therapeutic use - Google Patents
Cytotoxic agents comprising taxanes and their therapeutic use Download PDFInfo
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- A61K47/6851—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
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- A61K47/6881—Cluster-antibody conjugates, i.e. the modifying agent consists of a plurality of antibodies covalently linked to each other or of different antigen-binding fragments covalently linked to each other
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- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
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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.</SD OAB>
Claims (44)
1. A compound represented by formula (I):
wherein:
R1 is H, an electron withdrawing group, or an electron donating group, and R1' and R1" are the same or different, and are H, an electron withdrawing group, or an electron donating group;
R2 is heterocyclic, a linear, branched, or cyclic ester or ether having from 1 to carbon atoms or a carbamate of the formula -CNR10R11, wherein R10 and R11 are the same or different and are H, linear, branched or cyclic alkyl having 1 to 10 carbon atoms or aryl;
R3 is aryl, or a linear, branched, or cyclic alkyl having from 1 to 10 carbon atoms;
R4 is -OC(CH3)3 or phenyl;
R5 is a linking group; and R6 is heterocyclic, H, a linear, branched, or cyclic ester or ether having from 1 to 10 carbon atoms or a carbamate of the formula CNR10R11, wherein R10 and R11 are the same or different and are H, linear, branched or cyclic alkyl having 1 to 10 carbon atoms or aryl.
wherein:
R1 is H, an electron withdrawing group, or an electron donating group, and R1' and R1" are the same or different, and are H, an electron withdrawing group, or an electron donating group;
R2 is heterocyclic, a linear, branched, or cyclic ester or ether having from 1 to carbon atoms or a carbamate of the formula -CNR10R11, wherein R10 and R11 are the same or different and are H, linear, branched or cyclic alkyl having 1 to 10 carbon atoms or aryl;
R3 is aryl, or a linear, branched, or cyclic alkyl having from 1 to 10 carbon atoms;
R4 is -OC(CH3)3 or phenyl;
R5 is a linking group; and R6 is heterocyclic, H, a linear, branched, or cyclic ester or ether having from 1 to 10 carbon atoms or a carbamate of the formula CNR10R11, wherein R10 and R11 are the same or different and are H, linear, branched or cyclic alkyl having 1 to 10 carbon atoms or aryl.
2. The compound of claim 1, wherein R1 is F, NO2, CN, Cl, CHF2, CF3, -OCH3, -OCH2CH3, or -NR7R8, wherein:
R7 and R8 are the same or different and are linear, branched, or cyclic alkyl having 1 to 10 carbon atoms or simple or substituted aryl having 1 to 10 carbon atoms.
R7 and R8 are the same or different and are linear, branched, or cyclic alkyl having 1 to 10 carbon atoms or simple or substituted aryl having 1 to 10 carbon atoms.
3. The compound of claim 2, wherein R7 and R8 each has 1 to 4 carbon atoms.
4. The compound of claim 2 or 3, wherein R7 and R8 are the same.
5. The compound of claim 1, wherein R2 is -COC2H5, -CH2CH3, -CONHCH2CH3, -CO-morpholino, -CO-piperidino, -CO-piperazino, or -CO-N-methylpiperazino.
6. The compound of claim 1, wherein R5 is a thiol- or disulfide-containing linking group.
7. The compound of claim 6, wherein R5 is -(CH2)n SZ, -CO(CH2)n SZ, -(CH2)n CH(CH3)SZ, -CO(CH2)n CH(CH3)SZ, -(CH2)n C(CH3)2SZ, -CO(CH2)n C(CH3)2SZ, -CONR12(CH2)n SZ, -CONR12(CH2)n CH(CH3)SZ, -CONR12(CH2)n C(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, branched alkyl or cyclic alkyl having from 1 to 10 carbon atoms, or simple or substituted aryl having from 1 to 10 carbon atoms or heterocyclic, and R12 in addition can be H, X is a linear alkyl or branched alkyl having 1-10 carbon atoms, and n is an integer of 1 to 10.
8. The compound of claim 1, wherein R1 is in the meta position and R1' and R1"
are H.
are H.
9. A compound represented by formula (I):
wherein:
R1 is H, an electron withdrawing group, or an electron donating group, and R1' and R1" are the same or different, and are H, an electron withdrawing group, or an electron donating group;
R2 is heterocyclic, linear, branched, or cyclic ester or ether having from 1 to carbon atoms or a carbamate of the formula CNR10R11, wherein R10 and R11 are the same or different and are H, linear, branched or cyclic alkyl having 1 to 10 carbon atoms or aryl;
R3 is -CH=C(CH3)2;
R4 is -OC(CH3)3 or phenyl;
R5 is a linking group; and R6 is heterocyclic, H, a linear, branched, or cyclic ester or ether having from 1 to 10 carbon atoms or a carbamate of the formula CNR10R11, wherein R10 and R11 are the same or different and are H, linear, branched or cyclic alkyl having 1 to
wherein:
R1 is H, an electron withdrawing group, or an electron donating group, and R1' and R1" are the same or different, and are H, an electron withdrawing group, or an electron donating group;
R2 is heterocyclic, linear, branched, or cyclic ester or ether having from 1 to carbon atoms or a carbamate of the formula CNR10R11, wherein R10 and R11 are the same or different and are H, linear, branched or cyclic alkyl having 1 to 10 carbon atoms or aryl;
R3 is -CH=C(CH3)2;
R4 is -OC(CH3)3 or phenyl;
R5 is a linking group; and R6 is heterocyclic, H, a linear, branched, or cyclic ester or ether having from 1 to 10 carbon atoms or a carbamate of the formula CNR10R11, wherein R10 and R11 are the same or different and are H, linear, branched or cyclic alkyl having 1 to
10 carbon atoms or aryl.
10. The compound of claim 9, wherein R1 is F, NO2, CN, Cl, CHF2, CF3, -OCH3, -OCH2CH3, or -NR7R8, wherein:
R7 and R8 are the same or different and are linear, branched, or cyclic alkyl having 1 to 10 carbon atoms or simple or substituted aryl having 1 to 10 carbon atoms.
10. The compound of claim 9, wherein R1 is F, NO2, CN, Cl, CHF2, CF3, -OCH3, -OCH2CH3, or -NR7R8, wherein:
R7 and R8 are the same or different and are linear, branched, or cyclic alkyl having 1 to 10 carbon atoms or simple or substituted aryl having 1 to 10 carbon atoms.
11. The compound of claim 10, wherein R7 and R8 each has 1 to 4 carbon atoms.
12. The compound of claim 10 or 11, wherein R7 and R8 are the same.
13. The compound of claim 9, wherein R2 is -COC2H5, -CH2CH3, -CONHCH2CH3, -CO-morpholino, -CO piperidino, -CO-piperazino, or -CO-N-methylpiperazino.
14. The compound of claim 9, wherein R5 is a thiol- or disulfide-containing linking group.
15. The compound of claim 14, wherein R5 is -(CH2)n SZ, -CO(CH2)n SZ, -(CH2)n CH(CH3)SZ, -CO(CH2)n CH(CH3)SZ, -(CH2)n C(CH3)2SZ, -CO(CH2)n C(CH3)2SZ, -CONR12(CH2)n SZ, -CONR12(CH2)n CH(CH3)SZ, -CONR12(CH2)n C(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, branched alkyl or cyclic alkyl having from 1 to 10 carbon atoms, or simple or substituted aryl having from 1 to 10 carbon atoms or heterocyclic, and R12 in addition can be H, X is a linear alkyl or branched alkyl having 1-10 carbon atoms, and n is an integer of 1 to 10.
16. The compound of claim 9, wherein R1 is in the meta position and R1' and R1" are H.
17. A compound represented by formula (I):
wherein:
R1 is H, an electron withdrawing group, or an electron donating group, and R1' and R1" are the same or different, and are H, an electron withdrawing group, or an electron donating group;
R2 is a linking group;
R3 is aryl, or is a linear, branched, or cyclic alkyl having from 1 to 10 carbon atoms;
R4 is -OC(CH3)3 or phenyl;
R5 is heterocyclic, H, a linear, branched, or cyclic ester or ether having from 1 to 10 carbon atoms or a carbamate of the formula CNR10R11, wherein R10 and R11 are the same or different and are H, linear, branched or cyclic alkyl having 1 to 10 carbon atoms or aryl; and R6 is heterocyclic, H, a linear, branched, or cyclic ester or ether having from 1 to 10 carbon atoms or a carbamate of the formula CNR10R11, wherein R10 and R11 are the same or different and are H, linear, branched or cyclic alkyl having 1 to 10 carbon atoms or aryl.
wherein:
R1 is H, an electron withdrawing group, or an electron donating group, and R1' and R1" are the same or different, and are H, an electron withdrawing group, or an electron donating group;
R2 is a linking group;
R3 is aryl, or is a linear, branched, or cyclic alkyl having from 1 to 10 carbon atoms;
R4 is -OC(CH3)3 or phenyl;
R5 is heterocyclic, H, a linear, branched, or cyclic ester or ether having from 1 to 10 carbon atoms or a carbamate of the formula CNR10R11, wherein R10 and R11 are the same or different and are H, linear, branched or cyclic alkyl having 1 to 10 carbon atoms or aryl; and R6 is heterocyclic, H, a linear, branched, or cyclic ester or ether having from 1 to 10 carbon atoms or a carbamate of the formula CNR10R11, wherein R10 and R11 are the same or different and are H, linear, branched or cyclic alkyl having 1 to 10 carbon atoms or aryl.
18. The compound of claim 17, wherein at least one of R1 is F, NO2, CN, Cl, CHF2, CF3, -OCH3, -OCH2CH3, or -NR7R8 wherein:
R7 and R8 are the same or different and are linear, branched, or cyclic alkyl having 1 to 10 carbon atoms or simple or substituted aryl having 1 to 10 carbon atoms.
R7 and R8 are the same or different and are linear, branched, or cyclic alkyl having 1 to 10 carbon atoms or simple or substituted aryl having 1 to 10 carbon atoms.
19. The compound of claim 18, wherein R7 and R8 each has 1 to 4 carbon atoms.
20. The compound of claim 18 and 19, wherein R7 and R8 are the same.
21. The compound of claim 17, wherein R2 is a thiol- or disulfide-containing linking group.
22. The compound of claim 21 wherein R2 is -(CH2)n SZ, -CO(CH2)n SZ, -(CH2)n CH(CH3)SZ, -CO(CH2)n CH(CH3)SZ, -(CH2)n C(CH3)2SZ, -CO(CH2)n C(CH3)2SZ, -CONR12(CH2)n SZ, -CONR12(CH2)n CH(CH3)SZ, -CONR12(CH2)n C(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, branched alkyl or cyclic alkyl having from 1 to 10 carbon atoms, or simple or substituted aryl having from 1 to 10 carbon atoms or heterocyclic, and R12 in addition can be H, X is a linear alkyl or branched alkyl having 1-10 carbon atoms, and n is an integer of 1 to 10.
23. The compound of claim 17, wherein R5 is -COC2H5, -CH2CH3, -CONHCH2CH3, -CO-morpholino, -CO-piperidino, -CO-piperazino, or CO-N-methylpiperazino.
24. The compound of claim 17, wherein R1 is in the meta position and R1' and R1"
are H.
are H.
25. A compound represented by formula (I):
wherein:
R1 is H, an electron withdrawing group, or an electron donating group, and R1' and R1" are the same or different and are H, an electron withdrawing group, or an electron donating group;
R2 is heterocyclic, H a linear, branched, or cyclic ester or ether having from to 10 carbon atoms or a carbamate of the formula CNR10R11, wherein R10 and R11 are the same or different and are H, linear, branched or cyclic alkyl having 1 to 10 carbon atoms or aryl;
R3 is aryl, or is a linear, branched or cyclic alkyl having from 1 to 10 carbon atoms;
R4 is -OC(CH3)3 or phenyl;
R5 is heterocyclic, H, a linear, branched, or cyclic ester or ether having from 1 to 10 carbon atoms or a carbamate of the formula CNR10R11, wherein R10 and R11 are the same or different and are H, linear, branched or cyclic alkyl having 1 to 10 carbon atoms or aryl;
R6 is a linking group.
wherein:
R1 is H, an electron withdrawing group, or an electron donating group, and R1' and R1" are the same or different and are H, an electron withdrawing group, or an electron donating group;
R2 is heterocyclic, H a linear, branched, or cyclic ester or ether having from to 10 carbon atoms or a carbamate of the formula CNR10R11, wherein R10 and R11 are the same or different and are H, linear, branched or cyclic alkyl having 1 to 10 carbon atoms or aryl;
R3 is aryl, or is a linear, branched or cyclic alkyl having from 1 to 10 carbon atoms;
R4 is -OC(CH3)3 or phenyl;
R5 is heterocyclic, H, a linear, branched, or cyclic ester or ether having from 1 to 10 carbon atoms or a carbamate of the formula CNR10R11, wherein R10 and R11 are the same or different and are H, linear, branched or cyclic alkyl having 1 to 10 carbon atoms or aryl;
R6 is a linking group.
26. The compound of claim 25, wherein R1 is F, NO2, CN, Cl, CHF2, CF3, -OCH3, -OCH2CH3, or -NR7R8 wherein:
R7 and R8 are the same or different and are linear, branched, or cyclic alkyl having 1 to 10 carbon atoms or simple or substituted aryl having 1 to 10 carbon atoms.
R7 and R8 are the same or different and are linear, branched, or cyclic alkyl having 1 to 10 carbon atoms or simple or substituted aryl having 1 to 10 carbon atoms.
27. The compound of claim 26, wherein R7 and R8 each has 1 to 4 carbon atoms.
28. The compound of claim 26 or 27, wherein R7 and R8 are the same.
29. The compound of claim 25, wherein R2 is -COC2H5, -CH2CH3, -CONHCH2CH3, -CO-morpholino, -CO-piperidino, -CO-piperazino, or -CO-N-methylpiperazino.
30. The compound of claim 25, wherein R6 is a thiol- or disulfide-containing linking group.
31. The compound of claim 30, wherein R6 is -(CH2)n SZ, -CO(CH2)n SZ, -(CH2)n CH(CH3)SZ, -CO(CH2)n CH(CH3)SZ, -(CH2)n C(CH3)2SZ, -CO(CH2)n C(CH3)2SZ, -CONR12(CH2)n SZ, -CONR12(CH2)n CH(CH3)SZ, -CONR12(CH2)n C(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, branched alkyl or cyclic alkyl having from 1 to 10 carbon atoms, or simple or substituted aryl having from 1 to 10 carbon atoms or heterocyclic, and R12 in addition can be H, X is a linear alkyl or branched alkyl having 1-10 carbon atoms, and n is an integer of 1 to 10.
Z is H or SR, wherein R and R12 are the same or different and are linear alkyl, branched alkyl or cyclic alkyl having from 1 to 10 carbon atoms, or simple or substituted aryl having from 1 to 10 carbon atoms or heterocyclic, and R12 in addition can be H, X is a linear alkyl or branched alkyl having 1-10 carbon atoms, and n is an integer of 1 to 10.
32. The compound of claim 25, wherein R1 is in the meta position and R1' and R1"
are H.
are H.
33. A cytotoxic agent comprising one or more taxanes covalently 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, an electron withdrawing group, or an electron donating group, and R1' and R1" are the same or different and are H, an electron withdrawing group, or an electron donating group;
R2 is a heterocyclic, linear, branched, or cyclic ester or ether having from 1 to carbon atoms or a carbamate of the formula CNR10R11; wherein R10 and R11 are the same or different and are H, linear, branched or cyclic alkyl having 1 to 10 carbon atoms or aryl;
R3 is aryl, or is a linear, branched, or cyclic alkyl having from 1 to 10 carbon atoms;
R4 is -OC(CH3)3 or phenyl;
R5 is a linking group; and R6 is a heterocyclic, H, linear, branched, or cyclic ester or ether having from 1 to 10 carbon atoms or a carbamate of the formula CNR10R11, wherein R10 and R11 are the same or different and are H, linear, branched or cyclic alkyl having 1 to 10 carbon atoms or aryl.
wherein:
R1 is H, an electron withdrawing group, or an electron donating group, and R1' and R1" are the same or different and are H, an electron withdrawing group, or an electron donating group;
R2 is a heterocyclic, linear, branched, or cyclic ester or ether having from 1 to carbon atoms or a carbamate of the formula CNR10R11; wherein R10 and R11 are the same or different and are H, linear, branched or cyclic alkyl having 1 to 10 carbon atoms or aryl;
R3 is aryl, or is a linear, branched, or cyclic alkyl having from 1 to 10 carbon atoms;
R4 is -OC(CH3)3 or phenyl;
R5 is a linking group; and R6 is a heterocyclic, H, linear, branched, or cyclic ester or ether having from 1 to 10 carbon atoms or a carbamate of the formula CNR10R11, wherein R10 and R11 are the same or different and are H, linear, branched or cyclic alkyl having 1 to 10 carbon atoms or aryl.
34. A cytotoxic agent comprising one or more taxanes covalently 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, an electron withdrawing group, or an electron donating group, and R1' and R1" are the same or different and are H, an electron withdrawing group, or an electron donating group;
R2 is a heterocyclic, linear, branched, or cyclic ester or ether having from 1 to carbon atoms or a carbamate of the formula CNR10R11, wherein R10 and R11 are the same or different and are H, linear, branched or cyclic alkyl having 1 to 10 carbon atoms or aryl;
R3 is -CH=C(CH3)2;
R4 is -OC(CH3)3 or phenyl;
R5 is a linking group; and R6 is heterocyclic, H, a linear, branched, or cyclic ester or ether having from 1 to 10 carbon atoms or a carbamate of the formula CNR10R11, wherein R10 and R11 are the same or different and are H, linear, branched or cyclic alkyl having 1 to 10 carbon atoms or aryl.
wherein:
R1 is H, an electron withdrawing group, or an electron donating group, and R1' and R1" are the same or different and are H, an electron withdrawing group, or an electron donating group;
R2 is a heterocyclic, linear, branched, or cyclic ester or ether having from 1 to carbon atoms or a carbamate of the formula CNR10R11, wherein R10 and R11 are the same or different and are H, linear, branched or cyclic alkyl having 1 to 10 carbon atoms or aryl;
R3 is -CH=C(CH3)2;
R4 is -OC(CH3)3 or phenyl;
R5 is a linking group; and R6 is heterocyclic, H, a linear, branched, or cyclic ester or ether having from 1 to 10 carbon atoms or a carbamate of the formula CNR10R11, wherein R10 and R11 are the same or different and are H, linear, branched or cyclic alkyl having 1 to 10 carbon atoms or aryl.
35. A cytotoxic agent comprising one or more taxanes covalently 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, an electron withdrawing group, or an electron donating group, and R1' and R1" are the same or different and are H, an electron withdrawing group, or an electron donating group;
R2 is a linking group;
R3 is aryl, or is a linear, branched, or cyclic alkyl having from 1 to 10 carbon atoms;
R4 is -OC(CH3)3 or phenyl;
R5 is a heterocyclic, H, linear, branched, or cyclic ester or ether having from 1 to 10 carbon atoms or a carbamate of the formula CNR10R11, wherein R10 and R11 are the same or different and are H, linear, branched or cyclic alkyl having 1 to 10 carbon atoms or aryl; and R6 is heterocyclic, H, a linear, branched, or cyclic ester or ether having from 1 to 10 carbon atoms or a carbamate of the formula CNR10R11, wherein R10 and R11 are the same or different and are H, linear, branched or cyclic alkyl having 1 to 10 carbon atoms or aryl.
wherein:
R1 is H, an electron withdrawing group, or an electron donating group, and R1' and R1" are the same or different and are H, an electron withdrawing group, or an electron donating group;
R2 is a linking group;
R3 is aryl, or is a linear, branched, or cyclic alkyl having from 1 to 10 carbon atoms;
R4 is -OC(CH3)3 or phenyl;
R5 is a heterocyclic, H, linear, branched, or cyclic ester or ether having from 1 to 10 carbon atoms or a carbamate of the formula CNR10R11, wherein R10 and R11 are the same or different and are H, linear, branched or cyclic alkyl having 1 to 10 carbon atoms or aryl; and R6 is heterocyclic, H, a linear, branched, or cyclic ester or ether having from 1 to 10 carbon atoms or a carbamate of the formula CNR10R11, wherein R10 and R11 are the same or different and are H, linear, branched or cyclic alkyl having 1 to 10 carbon atoms or aryl.
36. A cytotoxic agent comprising one or more taxanes covalently 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, an electron withdrawing group, or an electron donating group, and R1' and R1" are the same or different and are H, an electron withdrawing group, or an electron donating group;
R2 is heterocyclic, H, a linear, branched, or cyclic ester or ether having from 1 to 10 carbon atoms or a carbamate of the formula CNR10R11, wherein R10 and R11 are the same or different and are H, linear, branched or cyclic alkyl having 1 to 10 carbon atoms or aryl;
R3 is aryl, or is a linear, branched or cyclic alkyl having from 1 to 10 carbon atoms;
R4 is -OC(CH3)3 or phenyl;
R5 is heterocyclic, H, a linear, branched, or cyclic ester or ether having from 1 to 10 carbon atoms or a carbamate of the formula CNR10R11, wherein R10 and R11, are the same or different and are H, linear, branched or cyclic alkyl having 1 to 10 carbon atoms or aryl;
R6 is a linking group.
wherein:
R1 is H, an electron withdrawing group, or an electron donating group, and R1' and R1" are the same or different and are H, an electron withdrawing group, or an electron donating group;
R2 is heterocyclic, H, a linear, branched, or cyclic ester or ether having from 1 to 10 carbon atoms or a carbamate of the formula CNR10R11, wherein R10 and R11 are the same or different and are H, linear, branched or cyclic alkyl having 1 to 10 carbon atoms or aryl;
R3 is aryl, or is a linear, branched or cyclic alkyl having from 1 to 10 carbon atoms;
R4 is -OC(CH3)3 or phenyl;
R5 is heterocyclic, H, a linear, branched, or cyclic ester or ether having from 1 to 10 carbon atoms or a carbamate of the formula CNR10R11, wherein R10 and R11, are the same or different and are H, linear, branched or cyclic alkyl having 1 to 10 carbon atoms or aryl;
R6 is a linking group.
37. A therapeutic composition comprising:
(A) a therapeutically effective amount of the cytotoxic agent of any one of claims 33, 34, 35 or 36; and (B) a pharmaceutically acceptable carrier.
(A) a therapeutically effective amount of the cytotoxic agent of any one of claims 33, 34, 35 or 36; and (B) a pharmaceutically acceptable carrier.
38. The cytotoxic agent of any one of claims 33, 34, 35, or 36 wherein the cell binding agent is selected from the group consisting of antibodies, an antibody fragment, interferons, lymphokines, hormones, vitamins, growth factors, colony stimulating factors, and transferrin.
39. The cytotoxic agent of any one of claims 33, 34, 35, or 36 wherein the cell binding agent is an antibody.
40. The cytotoxic agent of any one of claims 33, 34, 35, or 36 wherein the cell binding agent is a monoclonal antibody.
41. The cytotoxic agent of any one of claims 33, 34, 35, or 36 wherein the cell binding agent is an antigen specific antibody fragment.
42. The cytotoxic agent of any one of claims 33, 34, 35, or 36 wherein the antibody fragment is sFV, Fab, Fab', or F(ab')2.
43. The cytotoxic agent of any one of claims 33, 34, 35, or 36 wherein the cell binding agent is a growth factor or colony stimulating factor.
44. A method of killing selected cell populations comprising contacting target cells or tissue containing target cells with an effective amount of the cytotoxic agent of any one of claims 33, 34, 35 or 36.
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US16722899P | 1999-11-24 | 1999-11-24 | |
US60/167,228 | 1999-11-24 | ||
PCT/US2000/030149 WO2001038318A1 (en) | 1999-11-24 | 2000-11-21 | Cytotoxic agents comprising taxanes and their therapeutic use |
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AU (1) | AU765588C (en) |
CA (1) | CA2388063C (en) |
DE (1) | DE60032633T2 (en) |
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