Abstract
AbstractClofibrate (ethyl 2‐methyl‐2‐[4‐chlorophenoxy] propionate) is currently an important hypolipemic agent. In this study we describe the biological properties of certain acyclic and cyclic analogs of clofibrate in a hyperlipemic rat model in which the hyperlipemia was induced by ip injection of Triton WR‐1339. Cyclic analogs studied for their hypocholesterolemic and hypotriglyceridemic activities, as well as their ability to modify lipoprotein patterns, include the ethyl esters of 1,4‐benzodioxane‐2‐carboxylic acid, 6‐chlorochroman‐2‐carboxylic acid and 5‐chloro‐2,3‐dihydrobenzofuran‐2‐carboxylic acid. Among the clofibrate analogs, ethyl 6‐chlorochroman‐2‐carboxylate compares most favorably with the parent compound. Whereas the 6‐chlorochroman‐2‐carboxylate is effective as a hypocholesterolemic and hypotriglyceridemic agent, the 1,4‐benzodioxane analog exhibits mainly hypotriglyceridemic activity, while the 2,3‐dihydrobenzofuran analog exhibits hypocholesterolemic activity. Except for the benzodioxane, deschloro analogs are inactive. Results obtained in these studies are discussed in terms of structural requirements for biological activity and modes of action proposed for the parent drug clofibrate.
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