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

  • Bioorg Med Chem Lett. 2001 May 7;11(9):1225-7. doi: 10.1016/s0960-894x(01)00188-3.
P J Brown  1 ,  L W Stuart ,  K P Hurley ,  M C Lewis ,  D A Winegar ,  J G Wilson ,  W O Wilkison ,  O R Ittoop ,  T M Willson
Affiliations
PMID: 11354382 DOI: 10.1016/s0960-894x(01)00188-3
Abstract

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 PPARalpha agonist with approximately 200-fold selectivity over PPARgamma and PPARdelta, and potent lipid-lowering activity in animal models of dyslipidemia. GW7647 (3) will be a valuable chemical tool for studying the biology of PPARalpha in human cells and animal models of disease.

Products