Phenylenebis(oxy)bis[2,2-dimethylpentanoic acids]: agents that elevate high-density lipoproteins

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Abstract
A series of phenylenebis(oxy)bis[2,2-dimethylpentanoic acid]s were synthesized and evaluated as potential hypolipidemic agents. Compound 18 [5,5''-[[1,1''-biphenyl]-2,5-diylbis(oxy)]bis[2,2-dimethylpentanoic acid] (CI-924) was the most potent compound in this series. In rats, compound 18 not only reduced low-density lipoprotein cholesterol but also increased high-density lipoprotein (HDL) cholesterol. Comparative studies in rats indicated 18 produced an equal elevation of HDL cholesterol at 1/3 of the dose required of gemfibrozil. Structure-activity relationships are discussed.