58997-10-7Relevant articles and documents
Design, synthesis, and evaluation of potent RIPK1 inhibitors with in vivo anti-inflammatory activity
Li, Zhanhui,Hao, Yongjin,Yang, Chengkui,Yang, Qing,Wu, Shuwei,Ma, Haikuo,Tian, Sheng,Lu, Haohao,Wang, Jingrui,Yang, Tao,He, Sudan,Zhang, Xiaohu
, (2021/12/16)
RIPK1 plays a key role in the necroptosis pathway that regulates inflammatory signaling and cell death in various diseases, including inflammatory and neurodegenerative diseases. Herein, we report a series of potent RIPK1 inhibitors, represented by compound 70. Compound 70 efficiently blocks necroptosis induced by TNFα in both human and mouse cells (EC50 = 17–30 nM). Biophysical assay demonstrates that compound 70 potently binds to RIPK1 (Kd = 9.2 nM), but not RIPK3 (Kd > 10,000 nM). Importantly, compound 70 exhibits greatly improved metabolic stability in human and rat liver microsomes compared to compound 6 (PK68), a RIPK1 inhibitor reported in our previous work. In addition, compound 70 displays high permeability in Caco-2 cells and excellent in vitro safety profiles in hERG and CYP assays. Moreover, pre-treatment of 70 significantly ameliorates hypothermia and lethal shock in SIRS mice model. Lastly, compound 70 possesses favorable pharmacokinetic parameters with moderate clearance and good oral bioavailability in SD rat. Taken together, our work supports 70 as a potent RIPK1 inhibitor and highlights its potential as a prototypical lead for further development in necroptosis-associated inflammatory disorders.
Noncovalent Interactions in Ir-Catalyzed C-H Activation: L-Shaped Ligand for Para-Selective Borylation of Aromatic Esters
Hoque, Md Emdadul,Bisht, Ranjana,Haldar, Chabush,Chattopadhyay, Buddhadeb
supporting information, p. 7745 - 7748 (2017/06/21)
An efficient strategy for the para-selective borylation of aromatic esters is described. For achieving high para-selectivity, a new catalytic system has been developed modifying the core structure of the bipyridine. It has been proposed that the L-shaped ligand is essential to recognize the functionality of the oxygen atom of the ester carbonyl group via noncovalent interaction, which provides an unprecedented controlling factor for para-selective C-H activation/borylation.
DIMETHYLBENZOIC ACID COMPOUNDS
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Page/Page column 30-31, (2015/07/07)
The present invention provides a compound of the Formula I: wherein A is: and W, Y, X, R1, R2, R3, and R4 are as defined herein, or a pharmaceutically acceptable salt thereof, for use as an inhibitor of the EP4 receptor.
