Nara, Susheel J. published the artcileDiscovery of BMS-986339, a Pharmacologically Differentiated Farnesoid X Receptor Agonist for the Treatment of Nonalcoholic Steatohepatitis, Recommanded Product: (6-Ethoxypyridin-3-yl)boronic acid, the publication is Journal of Medicinal Chemistry (2022), 65(13), 8948-8960, database is CAplus and MEDLINE.
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.
Journal of Medicinal Chemistry published new progress about 612845-44-0. 612845-44-0 belongs to pyridine-derivatives, auxiliary class Pyridine,Boronic acid and ester,Ether,Boronic Acids,Boronic acid and ester, name is (6-Ethoxypyridin-3-yl)boronic acid, and the molecular formula is C7H10BNO3, Recommanded Product: (6-Ethoxypyridin-3-yl)boronic acid.
Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem