《Discovery of novel 2,8-diazaspiro[4.5]decan-1-one derivatives as potent RIPK1 kinase inhibitors》 was written by Niu, Ao; Lin, Lizhi; Zhang, Danyang; Jiang, Kaixuan; Weng, Dan; Zhou, Wenjia; Wang, Jinxin. COA of Formula: C7H6Cl2 And the article was included in Bioorganic & Medicinal Chemistry on April 1 ,2022. The article conveys some information:
Necroptosis, a key form of programmed lytic cell death, has gained recognition as an important driver in various inflammatory diseases. Inhibition of kinase activity of receptor interaction protein kinase 1 (RIPK1), which block the activation of the necroptosis pathway has shown therapeutic potential in many human diseases. In order to find new chemotypes of RIPK1 inhibitors, a virtual screening workflow was performed and led to the discovery of 8-benzoyl-3-benzyl-1,3,8-triazaspiro[4.5]decane-2,4-dione as a hit compound Further structural optimization identified a series of 2,8-diazaspiro[4.5]decan-1-one derivatives as potent RIPK1 inhibitors. Among them, compound 2-(2,5-difluorobenzyl)-8-(1-methyl-1H-indole-6-carbonyl)-2,8- diazaspiro[4.5]decan-1-one exhibited prominent inhibitory activity against RIPK1 with an IC50 value of 92 nM. Meanwhile, compound 2-(2,5-difluorobenzyl)-8-(1-methyl-1H-indole-6-carbonyl)-2,8- diazaspiro[4.5]decan-1-one showed a significant anti-necroptotic effect in a necroptosis model in U937 cells. Therefore, 2-(2,5-difluorobenzyl)-8-(1-methyl-1H-indole-6-carbonyl)-2,8- diazaspiro[4.5]decan-1-one could be employed as a lead compound of RIPK1 inhibitors for further structural optimization. In the part of experimental materials, we found many familiar compounds, such as 3-Chlorobenzylchloride(cas: 620-20-2COA of Formula: C7H6Cl2)
3-Chlorobenzylchloride(cas: 620-20-2) has been used in the reaction of 3-methoxybenzyl chloride and ethyl 4-bromobenzoate in pure water, using zinc dust and a Pd catalyst.COA of Formula: C7H6Cl2
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics