Identification of a subtype selective human PPARα agonist through parallel-array synthesis

Using solid-phase, parallel-array synthesis, a series of urea-substituted thioisobutyric acids was synthesized and assayed for activity on the human PPAR subtypes. GW7647 (3) was identified as a potent human PPAR alpha agonist with similar to 200-fold selectivity over PPAR gamma and PPAR delta, and potent lipid-lowering activity in animal models of dyslipidemia. GW7647 (3) will be a valuable chemical tool for studying the biology of PPAR alpha in human cells and animal models of disease. (C) 2001 Elsevier Science Ltd. Ail rights reserved.