VINYL SUBSTITUTED RADIOHALOGEN CONJUGATES FOR PROTEIN LABELING

摘要

Vinyl radiohalogenated small molecules as shown in formulas I and II: I IIwherein *X is a radiohalogen, C=C is a double bonded set of sp2 hybridized carbonatoms, and substituents R1, R2, and Y are as defined below. R1 and R2 aresubstituents independently selected from among hydrogen; alkyl or substitutedalkyl, provided that any sp2 or sp carbon atom substituted on the alkyl isseparated from C=C by at least one fully substituted sp3 carbon atom; aryl orsubstituted aryl, provided that the aryl is bonded directly to C=C; heteroalkyl,provided, first, that no heteroatom of the heteroalkyl bonds directly to C=C and,second, that any sp2 or sp hybridized carbon bonded to a heteroatom of theheteroalkyl is not bonded directly to or otherwise conjugated with C=C and, third,that where a single sp3 carbon intervenes between C=C and an sp2 or sp carbonbonded to a heteroatom, that intervening sp3 carbon must be fully substituted;heteroaryl, provided that a heteroatom of the heteroaryl is not bonded directlywith C=C; mixed alkylaryl, provided, first, that no heteroatom is bonded to C=Cand, second, that either an aryl moiety of the mixed alkylaryl is directly bonded toC=C or that any aryl moiety is separated from C=C by at least one sp3 carbonatom and, where only one sp3 hybridized carbon atom intervenes between C=C andan aryl moiety, that intervening sp3 carbon must be fully substituted. Y is asubstituent containing any of the groups described above for R1 and R2, exceptthat Y cannot be hydrogen, and bearing a functional group suitable for binding toprotein under conditions that preserve the biological activity of the protein. Thecompounds of formulas I and II can be coupled to proteins such as monoclonalantibodies to provide reagents for diagnostic and therapeutic applications. Alsometalated precursors of compounds I and II, as well as radiopharmaceuticalreagent kits containing any of the subject small molecules.