Discovery, synthesis and anti-atherosclerotic activities of a novel selective sphingomyelin synthase 2 inhibitor was written by Li, Yali;Huang, Taomin;Lou, Bin;Ye, Deyong;Qi, Xiangyu;Li, Xiaoxia;Hu, Shuang;Ding, Tingbo;Chen, Yan;Cao, Yang;Mo, Mingguang;Dong, Jibin;Wei, Min;Chu, Yong;Li, Huiti;Jiang, Xian-Cheng;Cheng, Nengneng;Zhou, Lu. And the article was included in European Journal of Medicinal Chemistry in 2019.Quality Control of 1-Bromo-6-chlorohexane The following contents are mentioned in the article:
The sphingomyelin synthase 2 (SMS2) is a potential target for pharmacol. intervention in atherosclerosis. However, so far, few selective SMS2 inhibitors and their pharmacol. activities were reported. In this study, a class of 2-benzyloxybenzamides were discovered as novel SMS2 inhibitors through scaffold hopping and structural optimization. Among them, Ly93 as one of the most potent inhibitors exhibited IC50 values of 91 nM and 133.9 μM against purified SMS2 and SMS1 resp. The selectivity ratio of Ly93 was more than 1400-fold for purified SMS2 over SMS1. The in vitro studies indicated that Ly93 not only dose-dependently diminished apoB secretion from Huh7 cells, but also significantly reduced the SMS activity and increased cholesterol efflux from macrophages. Meanwhile, Ly93 inhibited the secretion of LPS-mediated pro-inflammatory cytokine and chemokine in macrophages. The pharmacokinetic profiles of Ly93 performed on C57BL/6J mice demonstrated that Ly93 was orally efficacious. As a potent selective SMS2 inhibitor, Ly93 significantly decreased the plasma SM levels of C57BL/6J mice. Furthermore, Ly93 was capable of dose-dependently attenuating the atherosclerotic lesions in the root and the entire aorta as well as macrophage content in lesions, in apolipoprotein E gene knockout mice treated with Ly93. In conclusion, we discovered a novel selective SMS2 inhibitor Ly93 and demonstrated its anti-atherosclerotic activities in vivo. The preliminary mol. mechanism-of-action studies revealed its function in lipid homeostasis and inflammation process, which indicated that the selective inhibition of SMS2 would be a promising treatment for atherosclerosis. This study involved multiple reactions and reactants, such as 1-Bromo-6-chlorohexane (cas: 6294-17-3Quality Control of 1-Bromo-6-chlorohexane).
1-Bromo-6-chlorohexane (cas: 6294-17-3) belongs to organic chlorides. Organochlorines are organic compounds having multiple chlorine atoms. They were the first synthetic pesticides that were used in agriculture. They are resistant to most microbial and chemical degradations. Alkyl chlorides are versatile building blocks in organic chemistry. While alkyl bromides and iodides are more reactive, alkyl chlorides tend to be less expensive and more readily available.Quality Control of 1-Bromo-6-chlorohexane
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics