(Aryloxy)[p-(aryloxy)phenyl]- and (aryloxy)[p-(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.