COMPOUNDS WITH CHELATION AFFINITY AND SELECTIVITY FOR FIRST TRANSITION SERIES ELEMENTS AND THEIR USE IN MEDICAL THERAPY AND DIAGNOSIS

摘要

This invention involves synthesis and use of a class of compounds having formula (I), wherein, p and q are each independently integers of from 2 to 3; r is an integer of from 0 to 4; R?2, R3 and R4¿ are each independently selected from the group consisting of H, alkyl, alkenyl, aryl, arylalkyl, alkoxy, alkylthio, alkenoxy, alkenylthio, aryloxy, arylthio, alkyl interrupted by one or more oxa, alkenyl interrupted by one or more oxa, alkyl interrupted by thia, alkenyl interrupted by thia, aryloxyalkyl, alkoxyaryl, aminoalkyl, aminoalkenyl, aminoaryl, aminoarylalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyaryl, hydroxyarylalkyl, halogen substituted versions thereof; R1 is a member selected from the group consisting of R?2, R3, R4¿, and radicals of formula (V), and wherein, optionally, any two of R?1, R2, R3, and R4¿ are combined to form a ring structure; and dimers thereof, said dimers being formed by the covalent attachment of two complexing agents of formula (I) through a linking group having from 1 to 6 carbon atoms; and physiological salts thereof with the proviso that the molecular weight of said complexing agent does not exceed 2000, with chelation affinity and selectivity for first transition series elements. Administration of the free or conjugated compound, or physiological salts of the free or conjugated compound, results in decrease in the in vivo bioavailability of first transition series elements and/or removal from the body of first transition series elements and elements with similar chemical properties. Theses characteristics make such compounds useful in the management of diseases associated with a bodily excess of first transition series elements and elements with similar chemical properties. This invention demonstrates that such compounds inhibit mammalian, bacterial, and fungal cell replication and are therefore useful in the treatment of neoplasia, infection, inflammation, immune response, and in termination of pregnancy. Since these compounds are capable of decreasing the in vivo availability of tissue iron they are useful in management of free radical mediated tissue damage, and oxidation mediated tissue damage. When combined with radioisotopic or paramagnetic cations of first transition series elements, or elements with chemical properties similar to those of first transition series elements, prior to their administration, the resulting complexes are useful as diagnostic agents in nuclear medicine and magnetic resonance imaging (MRI).