In 2022,Nara, Susheel J.; Jogi, Srinivas; Cheruku, Srinivas; Kandhasamy, Sarkunam; Jaipuri, Firoz; Kathi, Pavan Kalyan; Reddy, Subba; Sarodaya, Sanket; Cook, Erica M.; Wang, Tao; Sitkoff, Doree; Rossi, Karen A.; Ruzanov, Max; Kiefer, Susan E.; Khan, Javed A.; Gao, Mian; Reddy, Satyanarayana; Sivaprasad LVJ, Sankara; Sane, Ramola; Mosure, Kathy; Zhuo, Xiaoliang; Cao, Gary G.; Ziegler, Milinda; Azzara, Anthony; Krupinski, John; Soars, Matthew G.; Ellsworth, Bruce A.; Wacker, Dean A. published an article in Journal of Medicinal Chemistry. The title of the article was 《Discovery of BMS-986339, a Pharmacologically Differentiated Farnesoid X Receptor Agonist for the Treatment of Nonalcoholic Steatohepatitis》.Formula: C4H7NO2S The author mentioned the following in the article:
While several farnesoid X receptor (FXR) agonists under clin. investigation for the treatment of nonalcoholic steatohepatitis (NASH) have shown beneficial effects, adverse effects such as pruritus and elevation of plasma lipids have limited their clin. efficacy and approvability. Herein, we report the discovery and preclin. evaluation of compound 32 (BMS-986339), a nonbile acid FXR agonist with a pharmacol. distinct profile relative to our previously reported agonist BMS-986318. Compound 32 exhibited potent in vitro and in vivo activation of FXR, albeit with a context-dependent profile that resulted in tissue-selective effects in vivo. To our knowledge, this is the first report that demonstrates differential induction of Fgf15 in the liver and ileum by FXR agonists in vivo. Compound 32 demonstrated robust antifibrotic efficacy despite reduced activation of certain genes in the liver, suggesting that the addnl. pharmacol. of BMS-986318 does not further benefit efficacy, possibly presenting an opportunity for reduced adverse effects. Further evaluation in humans is warranted to validate this hypothesis. In the part of experimental materials, we found many familiar compounds, such as Ethyl 2-amino-2-thioxoacetate(cas: 16982-21-1Formula: C4H7NO2S)
Ethyl 2-amino-2-thioxoacetate(cas: 16982-21-1) belongs to anime. Reduction of nitro compounds, RNO2, by hydrogen or other reducing agents produces primary amines cleanly (i.e., without a mixture of products), but the method is mostly used for aromatic amines because of the limited availability of aliphatic nitro compounds. Reduction of nitriles and oximes (R2C=NOH) also yields primary amines.Formula: C4H7NO2S
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