synthesis of a novel siliconized analog of clofibrate (silafibrate) and comparison of their anti-inflammatory activities

fibrates, as hypolipidemic drugs known as agonists of peroxisome proliferator-activated receptors, diminish inflammatory responses. studies have shown that incorporation of a silicon atom into a drug structure improves its pharmacological potency, modifies its selectivity toward a given target, or changes its metabolic rate, in addition to increasing the lipophilicity of the compounds. a siliconized analog of clofibrate, ethyl-2-methyl-2-(4-(trimethylsilyl)phenoxy)propionate was synthesized, whereby the chlorine atom in the phenoxy ring was replaced by a trimethylsilyl group. the anti-inflammatory effects of the siliconized analog (silafibrate) were evaluated in an air-pouch model of inflammation and compared with those of clofibrate. oral administration of both drugs produced a significant anti-inflammatory action by reducing carrageenan induced pouch leukocyte recruitment, exudates production, and granulated tissue weight. the silicon isostere of clofibrate has improved anti-inflammatory properties.