Structural Development Studies of Subtype-Selective Ligands for Peroxisome Proliferator-Activated Receptors (PPARs) Based on the 3,4-Disubstituted Phenylpropanoic Acid Scaffold as a Versatile Template

Improvements in our understanding of the functions of the nuclear receptor peroxisome proliferator-activated receptor (PPAR) subtypes as pleiotropic regulators of biological responses, including lipid, lipoprotein, glucose homeostasis, inflammation, differentiation and proliferation of various cancer cells, and memory, have provided an opportunity to develop novel PPAR ligands with characteristic subtype selectivity. Such ligands are not only chemical tools to investigate the functions of PPARs, but also candidates for the treatment of PPAR-mediated diseases, including metabolic syndrome, inflammation, dementia, and cancer. This minireview summarizes our work on the design, synthesis, and pharmacological evaluation of subtype-selective PPAR agonists based on the use of 3,4-disubstituted phenylpropanoic acid as a versatile template.