1359655-48-3

Upstream product

• 1609564-79-5 ethyl (2Z)-3-ethoxy-2-[(Z)-(3-methoxyphenyl)carbonyl]prop-2-enoate 
• 27834-99-7 ethyl (3-methoxybenzoyl)acetate 

Downstream Products

• 77212-18-1 C₁₆H₂₀N₂O₃ 
• 1303489-30-6 1-isopropyl-3-(3-methoxybenzyl)-1H-pyrazole-4-carboxylic acid 
• 1609565-02-7 N-((1-(3-methoxybenzyl)-3-(3-methoxyphenyl)-1H-pyrazol-4-yl)methyl)-4-methyl-3-(morpholinosulfonyl)aniline 
• 1609564-99-9 1-(3-methoxybenzyl)-3-(3-methoxyphenyl)-N-methyl-N-(4-methyl-3-(morpholinosulfonyl)phenyl)-1H-pyrazole-4-carboxamide 
• 1609564-94-4 1-(3-methoxybenzyl)-3-(3-methoxyphenyl)-N-(4-methyl-3-(morpholinosulfonyl) phenyl)-1H-pyrazole-4-carboxamide 
• 1609564-93-3 1-isopropyl-3-(3-methoxyphenyl)-N-(4-methyl-3-(morpholinosulfonyl)phenyl)-1H-pyrazole-4-carboxamide 
• 1609564-90-0 1-(3-methoxybenzyl)-3-(3-methoxyphenyl)-1H-pyrazole-4-carboxylic acid 

Relevant academic research and scientific papers

FARNESOID X RECEPTOR ANTAGONISTS

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

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.