| 摘要 |
This invention involves synthesis and use of a class of compounds having fomula (I) wherein: p and q are each independently integers of from 2 to 3; r is an integer of from 0 to 4; R2, R 3 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, alky l interrupted by thia, alkenyl interrupted by thia, aryloxyalkyl, alkoxyaryl, aminoalkyl, aminoalkenyl, aminoaryl, aminoarylalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyaryl, hydroxyarylalkyl, halogen substituted versions therof; R1 is a member selected from the group consisting of R2, R3, R4, and radicals of formula (V) and wherein, optionally, any two of R1, R2, R3 and R4 are combined to form a ring structure; said dimers therof, 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 atom;- and physiological salts thereof with the proviso that the molecular weight of said complexing agent does not exceed 2000, which 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. These characteristics make such compounds useful in the management of diseases associated with a bodily excess of firs t 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 reponse, and in termination of pregnancy. Since these compounds are capable of decreasing th e in vivo availability of tissue iron they are useful in management of free redical mediated tissue damage, and oxidation mediated tissue damage. When combined with radioisotopic or paramagnetic cations of first transition series elements, o r elements with chemical properties similar to those of first transition series elements, prior to their administration, th e resulting complexes are useful as diagnostic agents in nuclear medicine and magnetic resonance imaging (MRI).
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