Patent ID: 6881748

Claim:
A bioreductive conjugate comprising a bioreductive moiety with at least one therapeutic agent linked thereto and physiologically acceptable derivatives thereof wherein the bioreductive moiety incorporates an aromatic ring substituted with a nitro group and the conjugate is such that bioreduction of the nitro group causes release of the therapeutic agent by a through bond elimination and the residue of the bioreductive moiety to undergo an intramolecular cyclization reaction in which the nitrogen of the original nitro group provides an atom of the thus formed ring, wherein the therapeutic agent to be released on bioreduction is bonded to the aromatic ring via a side chain incorporating one or more double bonds which are located in the side chain between said therapeutic agent and the aromatic ring, which is/are conjugated to the aromatic ring, and which is/are displaceable to provide for elimination of said therapeutic moiety and formation of an arrangement of double bonds such that the residue of the bioreductive moiety is capable of undergoing the intramolecular cyclisation reaction, and wherein said conjugate is of the general formula (III) in which Drug is a therapeutic agent; X is a linker (which may be part of the drug) and is —NH,; R 1 , R 2 , and R 3 are hydrogen, and R 4 is a substituted or unsubstituted alkyl n is 1 to 3; and Z 1 is hydrogen, substituted or unsubstituted alkyl, aryl, halide, amine, alkoxy, ether, ester, alcohol, phenol, nitro, amide, thiol, sulphate, phosphate, or phosphonate.