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Discovery of INT131: a selective PPARγ modulator that enhances insulin sensitivity.

Abstract：

: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.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Taygerly JP,McGee LR,Rubenstein SM,Houze JB,Cushing TD,Li Y,Motani A,Chen JL,Frankmoelle W,Ye G,Learned MR,Jaen J,Miao S,Timmermans PB,Thoolen M,Kearney P,Flygare J,Beckmann H,Weiszmann J,Lindstrom M,Walker N,Li

doi

10.1016/j.bmc.2012.11.058

subject

Has Abstract

pub_date

2013-02-15 00:00:00

pages

979-92

issue

4

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(12)00953-4

journal_volume

21

pub_type

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