Journal
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Volume 19, Issue 9, Pages 2468-2473Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2009.03.036
Keywords
alpha-Alkoxypropionic acids; Nuclear hormone receptors; PPAR; X-ray crystallography; Diabetes; Dyslipidemia
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Design, synthesis, and SAR of novel alpha-alkoxy-beta-arylpropionic acids as potent and balanced PPAR alpha gamma coagonists are described. One representative thereof, Aleglitazar ((S)-2Aa), was chosen for clinical development. Its X-ray structure in complex with both receptors as well as its high efficacy in animal models of T2D and dyslipidemia are also presented. (c) 2009 Elsevier Ltd. All rights reserved.
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