Synthesis and biological evaluation of ester prodrugs of benzafibrate as orally active hypolipidemic agents

A series of bezafibrate ester prodrugs 1-7 were synthesized and evaluated for hypolipidemic activity in Swiss Albino mice (SAM). Bezafibrate (1a), a hypolipidemic drug was used as a reference compound for data comparison. Among the synthesized compounds, prodrug 7 showed superior activities in decreasing triglyceride up to 30% in mice plasma after oral administration of 50 mg/kg/day for 8 days. Prodrugs 2, 3, 5, 6, and 7 were found to be more lipophilic than bezafibrate (la), indicated by partition coefficients measured in octanol-buffer system at pH 7.4. On the basis of in vivo studies, prodrug 7 emerged as new potent hypolipidemic agent. (C) 2012 Elsevier Masson SAS. All rights reserved.