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

PJ Brown, LW Stuart, KP Hurley, MC Lewis… - Bioorganic & medicinal …, 2001 - Elsevier
PJ Brown, LW Stuart, KP Hurley, MC Lewis, DA Winegar, JG Wilson, WO Wilkison, OR Ittoop…
Bioorganic & medicinal chemistry letters, 2001Elsevier
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 PPARα agonist with∼ 200-fold selectivity over PPARγ and
PPARδ, and potent lipid-lowering activity in animal models of dyslipidemia. GW7647 (3) will
be a valuable chemical tool for studying the biology of PPARα in human cells and animal
models of disease.
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 PPARα agonist with ∼200-fold selectivity over PPARγ and PPARδ, and potent lipid-lowering activity in animal models of dyslipidemia. GW7647 (3) will be a valuable chemical tool for studying the biology of PPARα in human cells and animal models of disease.
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