244768-32-9Relevant articles and documents
Structural modifications of diarylpyrimidines (DAPYs) as HIV-1 NNRTIs: Synthesis, anti-HIV activities and SAR
Lu, Huan-Huan,Xue, Ping,Zhu, Yuan-Yuan,Ju, Xiu-Lian,Zheng, Xiao-Jiao,Zhang, Xun,Xiao, Ting,Pannecouque, Christophe,Li, Ting-Ting,Gu, Shuang-Xi
, p. 2491 - 2497 (2017)
30 new analogues of diarylpyrimidines were synthesized for further structural modifications, involving not only the linker but also the wing α of DAPYs. The anti-HIV-1 activities of all target molecules were evaluated, and most of them exhibited potent anti-HIV-1 (WT) activities and low cytotoxicities. Among which, compound 4g showed excellent activities against WT HIV-1 with an EC50 value of 5.8?nM and SI of up to 26,034. Another compound 4ab bearing a novel pyridinyl Wing α also displayed attractive activities. The structure-activity relationship (SAR) study was also summarized.
Design of biphenyl-substituted diarylpyrimidines with a cyanomethyl linker as HIV-1 NNRTIs via a molecular hybridization strategy
Chen, Fen-Er,Han, Sheng,Lei, Yuan,Pannecouque, Christophe,Yang, Yang,Zhuang, Chunlin,de Clercq, Erik
, (2020)
The key problems of human immunodeficiency virus (HIV) therapy are the rapid emergence of drug-resistant mutant strains and significant cumulative drug toxicities. Therefore, there is an urgent demand for new anti-HIV agents with low toxicity and broad-spectrum antiviral potency. A series of biphenyl-substituted diarylpyrimidines with a cyanomethyl linker were designed using a molecular hybridization strategy. The cell-based anti-HIV assay showed that most of the compounds exhibited moderate to good activities against wild-type HIV-1 and clinically relevant mutant strains with a more favorable toxicity, and the enzymatic assay showed they had nanomolar activity against reverse transcriptase (RT). Compound 10p exhibited the best activity against wild-type HIV-1 with an EC50 (50% HIV-1 replication inhibitory concentration) value of 0.027 μM, an acceptable CC50 (50% cytotoxic concentration) value of 36.4 μM, and selectivity index of 1361, with moderate activities against the single mutants (EC50: E138K, 0.17 μM; Y181C, 0.87 μM; K103N, 0.9 μM; L100I, 1.21 μM, respectively), and an IC50 value of 0.059 μM against the RT enzyme, which was six-fold higher than nevirapine (NVP). The preliminary structure–activity relationship (SAR) of these new compounds was concluded. The molecular modeling predicted the binding modes of the new compounds with RT, providing molecular insight for further drug design.
Exploiting the hydrophobic channel of the NNIBP: Discovery of novel diarylpyrimidines as HIV-1 NNRTIs against wild-type and K103N mutant viruses
Cherukupalli, Srinivasulu,De Clercq, Erik,Fu, Zhipeng,Gao, Shenghua,Kang, Dongwei,Liu, Xinyong,Pannecouque, Christophe,Sun, Lin,Zhan, Peng,Zhang, Tao,Zhou, Zhongxia
, (2021/07/22)
To further explore the chemical space surrounding the “hydrophobic channel” of the NNRTI binding pocket (NNIBP), a new series of diarylpyrimidines (DAPYs) were designed and synthesized as potent HIV-1 non-nucleoside RT inhibitors (NNRTIs). The target comp
Targeting the hydrophobic channel of NNIBP: Discovery of novel 1,2,3-triazole-derived diarylpyrimidines as novel HIV-1 NNRTIs with high potency against wild-type and K103N mutant virus
Zhou, Zhongxia,Liu, Tao,Wu, Gaochan,Kang, Dongwei,Fu, Zhipeng,Wang, Zhao,De Clercq, Erik,Pannecouque, Christophe,Zhan, Peng,Liu, Xinyong
, p. 3202 - 3217 (2019/03/26)
Enlightened by our previous efforts to modify diarylpyrimidines as HIV-1 non-nucleoside reverse transcriptase (RT) inhibitors (NNRTIs) and the reported crystallographic studies, we designed and synthesized novel 1,2,3-triazole-derived diarylpyrimidine der
