1033954-42-5Relevant articles and documents
Boronic acid-containing diarylpyrimidine derivatives as novel HIV-1 NNRTIs: Design, synthesis and biological evaluation
Feng, Da,Wei, Fenju,Sun, Yanying,Sharma, Prem Prakash,Zhang, Tao,Lin, Hao,Rathi, Brijesh,De Clercq, Erik,Pannecouque, Christophe,Kang, Dongwei,Zhan, Peng,Liu, Xinyong
, p. 4053 - 4057 (2021)
Drug resistance remains to be a serious problem with type I human immunodeficiency virus (HIV-1) non-nucleoside reverse transcriptase inhibitors (NNRTIs). A series of novel boronic acid-containing diarylpyrimidine (DAPY) derivatives were designed via bioisosterism and scaffold-hopping strategies, taking advantage of the ability of a boronic acid group to form multiple hydrogen bonds. The target compounds were synthesized and evaluated for their anti-HIV activities and cytotoxicity in MT-4 cells. Compound 10j yielded the most potent activity and turned out to be a single-digit nanomolar inhibitor towards the HIV-1 IIIB [wild-type (WT) strain], L100I and K103N strains, with 50% effective concentration (EC50) values of 7.19–9.85 nmol/L. Moreover, 10j inhibited the double-mutant strain RES056 with an EC50 value of 77.9 nmol/L, which was 3.3-more potent than that of EFV (EC50 = 260 nmol/L) and comparable to that of ETR (EC50 = 32.2 nmol/L). 10j acted like classical NNRTIs with high affinity for WT HIV-1 reverse transcriptase (RT) with 50% inhibition concentration (IC50) value of 0.1837 μmol/L. Furthermore, molecular dynamics simulation indicated that 10j was proposed as a promising molecule for fighting against HIV-1 infection through inhibiting RT activity. Overall, the results demonstrated that 10j could serve as a lead molecule for further modification to address virus-drug resistance.
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)
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
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
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
, (2020/12/07)
To yield potent HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) with favorable drug-like properties, a series of novel diarylpyrimidine derivatives targeting the tolerant region I of the NNRTI binding pocket were designed, synthesized and b
2,4,5-trisubstituted pyrimidine compound taking HIV-1 reverse transcriptase as target spot as well as preparation method and application thereof
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Paragraph 0035; 0038-0039, (2020/07/06)
The invention discloses a 2,4,5-trisubstituted pyrimidine compound taking HIV-1 reverse transcriptase as a target spot as well as a preparation method and application thereof. The compound has a structure as shown in a general formula I in the specificati
