Studies on antihyperlipidemic agents. II. Synthesis and biological activities of 2-chloro-3-arylpropionic acids.

alpha-Substituted-beta-arylpropionic acid derivatives were prepared and examined for hypolipidemic activity. The structure-activity relationship study showed that a chloro substituent at the alpha-position and an aryloxy or aralkyloxy substituent on the beta-aryl moiety was necessary for possession of substantial activity. In addition, some of these compounds showed hypolipidemic and hypoglycemic effects on diabetic mice. Among the 71 compounds prepared, ethyl 2-chloro-3-[4-(4-chlorobenzyloxy)phenyl]propionate (12) and ethyl 2-chloro-3-[4-(1-phenylethyloxy)phenyl]propionate (24) were the best with respect to activity and toxicity.