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

Authors
Brown, PJ Stuart, LW Hurley, KP Lewis, MC Winegar, DA Wilson, JG Wilkinson, WO Ittoop, OR Willson, TM
Citation
Pj. Brown et al., Identification of a subtype selective human PPAR alpha agonist through parallel-array synthesis, BIOORG MED, 11(9), 2001, pp. 1225-1227
Citations number
8
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN journal
0960894X → ACNP
Volume
11
Issue
9
Year of publication
2001
Pages
1225 - 1227
Database
ISI
SICI code
0960-894X(20010507)11:9<1225:IOASSH>2.0.ZU;2-D
Abstract
Using solid-phase, parallel-array synthesis, a series of urea-substituted t hioisobutyric acids was synthesized and assayed for activity on the human P PAR subtypes. GW7647 (3) was identified as a potent human PPAR alpha agonis t 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. A il rights reserved.