Recent Progress of Medicinal Chemistry Research on Peroxisome Proliferator-Activated Receptor (PPAR) Ligands for the Treatment of Metabolic Syndrome

Hiroyuki      Miyachi

Abstract

Improvements in our understanding of the functions of the nuclear receptor peroxisome proliferator-activated receptor (PPAR ) subtypes as master regulators of lipid, lipoprotein, and glucose homeostasis, and the rapid development of parallel screening assay methods to evaluate transactivation and/or binding activity toward individual PPAR subtypes, have provided an opportunity to develop novel PPAR agonists with characteristic subtype selectivity. Such agonists are candidates for the treatment of metabolic syndrome, which includes type II diabetes, dyslipidemia, obesity, and hypertension. This review focuses on the recent literature dealing with medicinal-chemical strategies to identify PPARδ- selective agonists and PPARδ/α dual agonists. Recent progress of studies on selective modulators of PPARγM (SPPARγM) is also briefly reviewed.

Keywords: Peroxisome proliferator-activated receptor, PPAR, PPARδ agonist, PPARδ/α dual agonist, SPPARγM