Design and synthesis of novel and potent amide linked PPARgamma/delta dual agonists.

Qing Shi,Emily J Canada,Yanping Xu,Alan M Warshawsky,Garret J Etgen,Carol L Broderick,Cathleen K Clutinger,Lynnie A Irwin,Michael E Laurila,Chahrzad Montrose-Rafizadeh,Brian A Oldham,Minmin Wang,Leonard L Winneroski,Chaoyu Xie,Jeremy S York,Nathan P Yumibe,Richard W Zink,Nathan Mantlo

Bioorganic & medicinal chemistry letters（2007）

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摘要

A series of potent amide linked PPARgamma/delta dual agonists (1a) has been discovered through rational design. In the ZDF rat model of type 2 diabetes, compound (R)-3-[4-(3-{1-[(5-chloro-1,3-dimethyl-1H-indole-2-carbonyl)-amino]-ethyl}-5-fluoro-phenoxy)-2-ethyl-phenyl]-propionic acid (42) from this series has demonstrated glucose lowering efficacy comparable to the marketed PPARgamma agonist rosiglitazone with less weight gain.

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