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Synthesis and evaluation of radioiodinated terminal p-iodophenyl-substituted alpha- and beta-methyl-branched fatty acids

Journal Article · · J. Med. Chem.; (United States)
DOI:https://doi.org/10.1021/jm00369a027· OSTI ID:6847258

Methods have been developed for the preparation of terminal p-idophenyl-substituted alpha- and beta-methyl-branched long-chain fatty acids. The syntheses and physical properties of 14-(p-iodophenyl)-2(RS)-methyltetradecanoic acid and 15-p-iodophenyl)-3(RS)-methylpentadecanoic acid are described. The radioiodinated agents are of interest as a result of the expected pronounced uptake and prolonged myocardial retention that may result from the inhibition of fatty acid metabolism. Tissue distribution studies in rats with 14-(p-(125I)iodophenyl)-2(RS)-methyltetradecanoic acid and 15-(p-(125I)iodophenyl)-3(RS)-methylpentadecanoic acid show significant heart uptake and prolonged retention accompanied by low in vivo deiodination and high blood levels. A comparison of the heart uptake of the radioiodinated methyl-branched fatty acids and their unbranched analogues has demonstrated a greater myocardial retention of the methyl-branched fatty acids than the unbranched analogues. These results suggest that the mechanism of myocardial retention results from steric or chemical inhibition of the metabolism of these fatty acids by the presence of the methyl group.

Research Organization:
Health and Safety Research Division, Oak Ridge National Laboratory, Tennessee
OSTI ID:
6847258
Journal Information:
J. Med. Chem.; (United States), Journal Name: J. Med. Chem.; (United States) Vol. 27:3; ISSN JMCMA
Country of Publication:
United States
Language:
English