(ARYLOXY)[PARA-(ARYLOXY)PHENYL]ACETIC AND (ARYLOXY)[PARA-(ARYLTHIO)PHENYL]ACETIC ACIDS AND ESTERS AS HYPOLIPIDEMIC AGENTS

A series of (aryloxy)[p-(aryloxy)phenyl]- and (aryloxy)[p-(arylthio)phenyl]acetic acids and esters of general structure 8 were prepared and tested for lipid-lowering activity in normal rats. At a dose of 0.1% of the diet (ca. 100 mg/kg), approximately half of the compounds reduced serum sterols in the range of 20-30% and lowered serum triglycerides by 40-60%. Over 35 analogues lowered serum sterols by 15-25% when fed at 0.03% of diet, and 15 of these maintained their activity at 0.01% of the diet (10 mg/kg). Synthetic methodology and structure-activity relationships are discussed. © 1979, American Chemical Society. All rights reserved.