158196-47-5Relevant articles and documents
Design, synthesis, and biological studies of novel 3-benzamidobenzoic acid derivatives as farnesoid X receptor partial agonist
Hu, Lijun,Ren, Qiang,Deng, Liming,Zhou, Zongtao,Cai, Zongyu,Wang, Bin,Li, Zheng
, (2020/12/25)
Farnesoid X receptor (FXR), a bile acid-activated nuclear receptor, regulates the metabolism of bile acid and lipids as well as maintains the stability of internal environment. FXR was considered as a therapeutic target of liver disorders, such as drug-induced liver injury, fatty liver and cholestasis. The previous reported FXR partial agonist 6 was a suitable lead compound in terms of its high potent and low molecular size, while the docking study of compound 6 suggested a large unoccupied hydrophobic pocket, which might be provided more possibility of structure-activity relationship (SAR) study. In this study, we have performed comprehensive SAR and molecular modeling studies based on lead compound 6. All of these efforts resulted in the identification of a novel series of FXR partial agonists. In this series, compound 41 revealed the best activity and strong interaction with binding pocket of FXR. Moreover, compound 41 protected mice against acetaminophen-induced hepatotoxicity by the regulation of FXR-related gene expression and improving antioxidant capacity. In summary, these results suggest that compound 41 is a promising FXR partial agonist suitable for further investigation.
Selective Janus Kinase 2 (JAK2) Pseudokinase Ligands with a Diaminotriazole Core
Liosi, Maria-Elena,Krimmer, Stefan G.,Newton, Ana S.,Dawson, Thomas K.,Puleo, David E.,Cutrona, Kara J.,Suzuki, Yoshihisa,Schlessinger, Joseph,Jorgensen, William L.
, p. 5324 - 5340 (2020/06/10)
Janus kinases (JAKs) are non-receptor tyrosine kinases that are essential components of the JAK-STAT signaling pathway. Associated aberrant signaling is responsible for many forms of cancer and disorders of the immune system. The present focus is on the d
Pyrrolidinyl phenylurea derivatives as novel CCR3 antagonists
Nitta, Aiko,Iura, Yosuke,Inoue, Hideki,Imaoka, Takayuki,Takahashi, Toshiya,Sato, Ippei,Morihira, Koichiro,Kubota, Hirokazu,Morokata, Tatsuaki,Takeuchi, Makoto,Ohta, Mitsuaki,Tsukamoto, Shin-Ichi
, p. 6876 - 6881,6 (2020/09/02)
Optimization starting with our lead compound 1 (IC50 = 4.9 nM) led to the identification of pyrrolidinyl phenylurea derivatives. Further modification toward improvement of the bioavailability provided (R)-1-(1-((6-fluoronaphthalen-2-yl)methyl)pyrrolidin-3-yl)-3-(2-(2- hydroxyethoxy)phenyl)urea 32 (IC50 = 1.7 nM), a potent and orally active CCR3 antagonist.