Novel oxazole containing phenylpropane derivatives as peroxisome proliferator activated receptor agonists with hypolipidemic activity.

α-Alkoxy arylpropanoic acids containing 2-phenyloxazole-4yl-alkyl moiety are found to be potent hypolipidemic agents. These compounds were potent activators of the peroxisome proliferator activated receptor y (PPARy), with moderate PPARa activity and known to cause adverse effects such as weight gain and edema, which are essentially attributed to PPARy activation. Although extensive work has been done on the phenylpropanoic acid class of compounds, other phenyl propane derivatives such as alcohols, amines, ethers etc. have not received much attention. In order to develop predominant PPARa agonists as hypolipidemic agents with minor chemical modifications on compound III, we have synthesised few (2S)-ethoxyphenylpropane derivatives containing a 2-phenyl-5-methyloxazole-4ylalkoxy moiety of the general formula IV and evaluated by PPARa and y transactivation assay in conjugation with in vivo studies in male Swiss albino mice model. Compounds 3c and 3d showed the desired predominant PPARa activity and excellent tryiglyceride reduction in vivo and were selected as lead compounds for further development as hypolipidemic agents.