244767-99-5Relevant articles and documents
Design, synthesis, and evaluation of “dual-site”-binding diarylpyrimidines targeting both NNIBP and the NNRTI adjacent site of the HIV-1 reverse transcriptase
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
, (2021)
Inspired by our previous efforts 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 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 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 14c (EC50 = 2.45 nM) proved to be the most promising inhibitor. Of note, 14c 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 compound 7 (EC50 = 37.3 nM). Moreover, 14c acted as a classical NNRTI with high affinity for WT HIV-1 RT (IC50 = 0.0589 μM). The detailed structure-activity relationships (SARs) of the representative compounds were also determined, and further supported by molecular dynamics simulation. Overall, we envision that 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.
5-site aromatic ring substituted diarylpyrimidine derivative as well as preparation method and application thereof
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, (2020/11/22)
The invention provides a diarylpyrimidine derivative substituted by a 5-site aromatic ring. The diarylpyrimidine derivative has a structure as shown in a general formula I which is described in the specification. The invention also relates to a preparation method of the derivative and application of the derivative as an HIV inhibitor in preparation of anti-AIDS drugs.
Discovery of Novel Diarylpyrimidine Derivatives as Potent HIV-1 NNRTIs Targeting the "nNRTI Adjacent" Binding Site
Huo, Zhipeng,Zhang, Heng,Kang, Dongwei,Zhou, Zhongxia,Wu, Gaochan,Desta, Samuel,Zuo, Xiaofang,Wang, Zhao,Jing, Lanlan,Ding, Xiao,Daelemans, Dirk,De Clercq, Erik,Pannecouque, Christophe,Zhan, Peng,Liu, Xinyong
, p. 334 - 338 (2018/04/19)
A novel series of diarylpyrimidine derivatives, which could simultaneously occupy the classical NNRTIs binding pocket (NNIBP) and the newly reported "NNRTI Adjacent" binding site, were designed, synthesized, and evaluated for their antiviral activities in
