1308436-41-0Relevant academic research and scientific papers
FARNESOID X RECEPTOR ANTAGONISTS
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, (2015/09/23)
Provided herein are Farnesoid X receptor (FXR) antagonists, methods of antagonizing FXR, and methods of treating metabolic disease using the antagonists herein.
Identification of trisubstituted-pyrazol carboxamide analogs as novel and potent antagonists of farnesoid X receptor
Yu, Donna D.,Lin, Wenwei,Forman, Barry M.,Chen, Taosheng
, p. 2919 - 2938 (2014/05/20)
Farnesoid X receptor (FXR, NRIH4) plays a major role in the control of cholesterol metabolism. This suggests that antagonizing the transcriptional activity of FXR is a potential means to treat cholestasis and related metabolic disorders. Here we describe the synthesis, biological evaluation, and structure-activity relationship (SAR) studies of trisubstituted-pyrazol carboxamides as novel and potent FXR antagonists. One of these novel FXR antagonists, 4j has an IC50 of 7.5 nM in an FXR binding assay and 468.5 nM in a cell-based FXR antagonistic assay. Compound 4j has no detectable FXR agonistic activity or cytotoxicity. Notably, 4j is the most potent FXR antagonist identified to date; it has a promising in vitro profile and could serve as an excellent chemical tool to elucidate the biological function of FXR.
