Rational Design and Synthesis of Potential Antisickling Agents: Second Year

摘要

It was found that when clofibric, a known antilipemic drug, was tested as its active metabolite, clofibric acid, it had significant activity in solubilizing deoxy HbS at 20 and 40 mM. Structural variation of clofibric acid produced a series of compounds which gave insights as to the parameters needed for activity in this series. X-ray crystallographic and biochemical studies have demonstrated different binding sites for clofibric acid with Hb and Hb CO. Structure activity studies with the benzyloxy series produced 3,4, dichlorobenzyloxyacetic acid (DiClBzOAc) a very active compound. A third series of compounds represented by meta di substituted benzoic acids were synthesized and found to be in the high activity range for solubilizing HbS. A new assay to measure antisickling activity with whole cells using a pressure filtration system has been initiated.