《Discovery and Optimization of Non-bile Acid FXR Agonists as Preclinical Candidates for the Treatment of Nonalcoholic Steatohepatitis》 was written by Li, Junyou; Liu, Mengqi; Li, Yazhou; Sun, Dan-dan; Shu, Zhihao; Tan, Qian; Guo, Shimeng; Xie, Rongrong; Gao, Lixin; Ru, Hongbo; Zang, Yi; Liu, Hong; Li, Jia; Zhou, Yu. Product Details of 29682-15-3 And the article was included in Journal of Medicinal Chemistry in 2020. The article conveys some information:
Farnesoid X receptor (FXR) plays a key role in bile acid homeostasis, inflammation, fibrosis, and metabolism of lipid and glucose and becomes a promising therapeutic target for nonalcoholic steatohepatitis (NASH) or other FXR-dependent diseases. The phase III trial results of obeticholic acid demonstrate that the FXR agonists emerge as a promising intervention in patients with NASH and fibrosis, but this bile acid-derived FXR agonist brings severe pruritus and an elevated risk of cardiovascular disease for patients. Herein, we reported our efforts in the discovery of a series of non-bile acid FXR agonists, and 36 compounds were designed and synthesized based on the structure-based drug design and structural optimization strategies. Particularly, compound 42(I) is a highly potent and selective FXR agonist, along with good pharmacokinetic profiles, high liver distribution, and preferable in vivo efficacy, indicating that it is a potential candidate for the treatment of NASH or other FXR-dependent diseases. The results came from multiple reactions, including the reaction of Methyl 5-bromopicolinate(cas: 29682-15-3Product Details of 29682-15-3)
Methyl 5-bromopicolinate(cas: 29682-15-3) belongs to pyridine. When pyridine is adsorbed on oxide surfaces or in porous materials, the following species are commonly observed: (i) pyridine coordinated to Lewis acid sites, (ii) pyridine H-bonded to weakly acidic hydroxyls, and (iii) protonated pyridine. At high coverage, physisorbed pyridine and protonated dimers can also be observed.Product Details of 29682-15-3