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.

Studies on antihyperlipidemic agents. III. Synthesis and biological activities of 2-chloro-3-arylpropionic acids containing a quarternary carbon atom.

A series of 2-chloro-3-(4-alkoxyphenyl)propionic acids containing a quarternary carbon atom in the alkoxy moiety was prepared and the hypolipidemic and hypoglycemic activities were evaluated. Of the 18 compounds synthesized, ethyl 2-chloro-3-[4-(2-methyl-2-phenylpropyloxy)phenyl]propionate (1) was the best with respect to biological activity and toxicity. Its functional derivatives and optically resolved enantiomers were also prepared. Structure-activity relationships are discussed briefly.

Studies on antihyperlipidemic agents. I. Synthesis and hypolipidemic activities of phenoxyphenyl alkanoic acid derivatives.

The alkanoic acids containing phenoxyphenyl moiety at omega-position were prepared and tested for hypolipidemic property. Some of the compounds showed hypoglycemic activity besides hypolipidemic one. Further study on the selected compound, 3-[4-(4-chlorophenoxy)benzoyl] propionic acid (8) revealed that it increased insulin sensitivity of adipose tissue of obese and diabetic mice (KKAY). The structure-activity relationship was discussed briefly.