Phenoxyacetic acids as PPAR¦Ä partial agonists: Synthesis, optimization, and in vivo efficacy

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• 作者：Karen A. Evans^a ; ^{karen.a.evans@gsk.com} ; Barry G. Shearer^b ; David D. Wisnoski^a ; Dongchuan Shi^a ; Steven M. Sparks^b ; Daniel D. Sternbach^b ; Deborah A. Winegar^b ; Andrew N. Billin^b ; Christy Britt^b ; James M. Way^b ; Andrea H. Epperly^b ; Lisa M. Leesnitzer^c ; Raymond V. Merrihew^c ; Robert X. Xu^c ; Millard H. Lambert^c ; Jian Jin^a
• 关键词：PPARd ; Partial agonist
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2011
• 出版时间：15 April, 2011
• 年：2011
• 卷：21
• 期：7
• 页码：2345-2350
• 全文大小：1K

文摘

A series of phenoxyacetic acids as subtype selective and potent hPPAR¦Ä partial agonists is described. Many analogues were readily accessible via a single solution-phase synthetic route which resulted in the rapid identification of key structure-activity relationships (SAR), and the discovery of two potent exemplars which were further evaluated in vivo. Details of the SAR, optimization, and in vivo efficacy of this series are presented herein.