Discovery of 4-Benzyloxybenzo[d]isoxazole-3-amine Derivatives as Highly Selective and Orally Efficacious Human Sphingomyelin Synthase 2 Inhibitors that Reduce Chronic Inflammation in db/db Mice was written by Mo, Mingguang;Yang, Jintong;Jiang, Xian-Cheng;Cao, Yu;Fei, Jinyu;Chen, Yang;Qi, Xiangyu;Chu, Yong;Zhou, Lu;Ye, Deyong. And the article was included in Journal of Medicinal Chemistry in 2018.Category: bromides-buliding-blocks This article mentions the following:
Sphingomyelin synthase 2 (SMS2) is a promising therapeutic target for several chronic inflammation-associated diseases, including atherosclerosis, fatty liver and insulin resistance. Herein, we report the identification of 4-benzyloxybenzo[d]isoxazole-3-amine derivatives as potent and highly selective SMS2 inhibitors through a conformational restriction strategy. After systematic structural modifications, several compounds with high selectivity and good potency in vitro were selected for further evaluation. Compound I demonstrated good pharmacokinetics (oral bioavailability, F = 56%) in vivo and has an inhibitory potency against sphingomyelin synthase activity when ICR (Institute of Cancer Research) mice are provided with an oral dose of this compound In addition, compound I attenuated chronic inflammation significantly in db/db mice after oral dosing for 6 wk. In the experiment, the researchers used many compounds, for example, 2-(Bromomethyl)-1,3-dimethylbenzene (cas: 83902-02-7Category: bromides-buliding-blocks).
2-(Bromomethyl)-1,3-dimethylbenzene (cas: 83902-02-7) belongs to organobromine compounds. Many of the organo bromine compounds are relatively nonpolar. Bromine is more electronegative than carbon (2.8 vs 2.5) and hence the carbon in a carbon–bromine bond is electrophilic in nature. The principal reactions for organobromides include dehydrobromination, Grignard reactions, reductive coupling, and nucleophilic substitution.Category: bromides-buliding-blocks
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary