Discovery of 2-((2-methylbenzyl)thio)-6-oxo-4-(3,4,5-trimethoxyphenyl)-1,6-dihydropyrimidine-5-carbonitrile as a novel and effective bromodomain and extra-terminal (BET) inhibitor for the treatment of sepsis

In this study, compound 1 was obtained through virtual screening, and candidate compound 27 was obtained through several rounds of iterative SAR analysis. 27 decreased LPS-induced NO production and expression of the pro-inflammatory factors IL-6, IL-1β and TNF-α. In vivo, 27 effectively protected mice from LPS-induced sepsis, increased survival rate and decreased the level of pro-inflammatory factors in serum. Collectively, we reported here 27, a BRD4 inhibitor with a new scaffold, as a potential candidate for the treatment of sepsis.PMID:35544982 | DOI:10.1016/j.ejmech.2022.114423

Source: European Journal of Medicinal Chemistry - May 11, 2022 Category: Chemistry Authors: Xuetao Chen Fanying Meng Jingtian Zhang Zijian Zhang Xuan Ye Weikun Zhang Yuanyuan Tong Xinrui Ji Rujun Xu Xiao-Li Xu Qi-Dong You Zheng-Yu Jiang Source Type: research