235427-10-8Relevant articles and documents
Discovery of INT131: A selective PPARγ modulator that enhances insulin sensitivity
Taygerly, Joshua P.,McGee, Lawrence R.,Rubenstein, Steven M.,Houze, Jonathan B.,Cushing, Timothy D.,Li, Yang,Motani, Alykhan,Chen, Jin-Long,Frankmoelle, Walter,Ye, Guosen,Learned, Marc R.,Jaen, Juan,Miao, Shichang,Timmermans, Pieter B.,Thoolen, Martin,Kearney, Patrick,Flygare, John,Beckmann, Holger,Weiszmann, Jennifer,Lindstrom, Michelle,Walker, Nigel,Liu, Jinsong,Biermann, Donna,Wang, Zhulun,Hagiwara, Atsushi,Iida, Tetsuya,Aramaki, Hisateru,Kitao, Yuki,Shinkai, Hisashi,Furukawa, Noboru,Nishiu, Jun,Nakamura, Motonao
, p. 979 - 992 (2013/03/28)
PPARγ is a member of the nuclear hormone receptor family and plays a key role in the regulation of glucose homeostasis. This Letter describes the discovery of a novel chemical class of diarylsulfonamide partial agonists that act as selective PPARγ modulators (SPPARγMs) and display a unique pharmacological profile compared to the thiazolidinedione (TZD) class of PPARγ full agonists. Herein we report the initial discovery of partial agonist 4 and the structure-activity relationship studies that led to the selection of clinical compound INT131 (3), a potent PPARγ partial agonist that displays robust glucose-lowering activity in rodent models of diabetes while exhibiting a reduced side-effects profile compared to marketed TZDs.
