Feng, Da; Zuo, Xiaofang; Jing, Lanlan; Chen, Chin-Ho; Olotu, Fisayo A.; Lin, Hao; Soliman, Mahmoud; De Clercq, Erik; Pannecouque, Christophe; Lee, Kuo-Hsiung; Kang, Dongwei; Liu, Xinyong; Zhan, Peng published their research in European Journal of Medicinal Chemistry in 2021. The article was titled 《Design, synthesis, and evaluation of “”dual-site””-binding diarylpyrimidines targeting both NNIBP and the NNRTI adjacent site of the HIV-1 reverse transcriptase》.Product Details of 3934-20-1 The article contains the following contents:
To improve the drug-resistance profiles of HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs), a novel series of “”dual-site”” binding diarylpyrimidine (DAPY) derivatives I [R1 = H, cyclopropyl, propargyl, etc.] and II [X = 1-R2-piperidin-4-yl, 1-R2-piperidin-4-ylmethyl, 1-R2-pyrrolidin-3-yl; R2 = methylsulfonyl, trifluoromethylsulfonyl, trifluoromethylcarbonyl, etc.] targeting both the NNRTI adjacent site and NNRTIs binding pocket (NNIBP) were designed, synthesized and evaluated for their anti-HIV potency in TZM-bl and MT-4 cells. Eight compounds I and II exhibited moderate to excellent potencies in inhibiting wild-type (WT) HIV-1 replication with EC50 values ranging from 2.45 nM to 5.36 nM, and I [R1 = propargylamino] (EC50 = 2.45 nM) proved to be the most promising inhibitor. Of note, I [R1 = propargylamino] exhibited potent activity against the single mutant strain E138K (EC50 = 10.6 nM), being comparable with ETR (EC50 = 9.80 nM) and 3.5-fold more potent than that of morpholino pyrimidine compound (EC50 = 37.3 nM). Moreover, I [R1 = propargylamino] acted as a classical NNRTI with high affinity for WT HIV-1 RT (IC50 = 0.0589μM). The detailed structure-activity relationships (SARs) of the representative compounds were also determined, and further supported by mol. dynamics simulation. Overall, the “”dual-site””-binding NNRTIs have significant prospects and pave the way for the next round of rational design of potent anti-HIV-1 agents. In the experiment, the researchers used 2,4-Dichloropyrimidine(cas: 3934-20-1Product Details of 3934-20-1)
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.Product Details of 3934-20-1
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia