Jiang, Xiangyi; Huang, Boshi; Olotu, Fisayo A.; Li, Jing; Kang, Dongwei; Wang, Zhao; De Clercq, Erik; Soliman, Mahmoud E. S.; Pannecouque, Christophe; Liu, Xinyong; Zhan, Peng published their research in European Journal of Medicinal Chemistry in 2021. The article was titled 《Exploiting the tolerant region I of the non-nucleoside reverse transcriptase inhibitor (NNRTI) binding pocket. Part 2: Discovery of diarylpyrimidine derivatives as potent HIV-1 NNRTIs with high Fsp3 values and favorable drug-like properties》.Name: 2,4-Dichloropyrimidine The article contains the following contents:
A series of novel diarylpyrimidine derivatives I [R1 = cyano, 2-cyanovinyl; R = thiomorpholino, 1-oxo-1,4-thiazinan-4-yl, 1,1-dioxo-1,4-thiazinan-4-yl, etc.] targeted the tolerant region I of the NNRTI binding pocket were designed, synthesized and biol. evaluated as potent HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) with favorable drug-like properties was studied. The most active inhibitor I [R1 = 2-cyanovinyl; R = 1,1-dioxo-1,4-thiazinan-4-yl] exhibited outstanding antiviral activity against most of the viral panel, being about 2-fold (wild-type, EC50 = 0.0021μM), 1.7-fold (K103N, EC50 = 0.0019μM), and slightly more potent (E138K, EC50 = 0.0075μM) than the NNRTI drug etravirine (ETR). Addnl., I [R1 = 2-cyanovinyl; R = 1,1-dioxo-1,4-thiazinan-4-yl] was endowed with relatively low cytotoxicity (CC50 = 18.52μM). More importantly, I [R1 = 2-cyanovinyl; R = 1,1-dioxo-1,4-thiazinan-4-yl] possessed improved drug-like properties compared to those of ETR with an increased F sp3 (Fraction of sp3 carbon atoms) value. Furthermore, the mol. dynamics simulation and mol. docking studies were implemented to reveal the binding mode of I [R1 = 2-cyanovinyl; R = 1,1-dioxo-1,4-thiazinan-4-yl] in the binding pocket. Taken together, I [R1 = 2-cyanovinyl; R = 1,1-dioxo-1,4-thiazinan-4-yl] was a promising lead compound that was worth further investigation. In the experimental materials used by the author, we found 2,4-Dichloropyrimidine(cas: 3934-20-1Name: 2,4-Dichloropyrimidine)
2,4-Dichloropyrimidine(cas: 3934-20-1) is a member of organic chlorides. Organic chloride content in crude oil can be detected through specialized laboratory analysis. Care and attention are essential while sampling and testing.Name: 2,4-Dichloropyrimidine
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia