Structural modifications of diarylpyrimidines (DAPYs) as HIV-1 NNRTIs: Synthesis, anti-HIV activities and SAR

Bioorg Med Chem. 2017 Apr 15;25(8):2491-2497. doi: 10.1016/j.bmc.2017.03.009.

Huan-Huan Lu ¹, Ping Xue ¹, Yuan-Yuan Zhu ², Xiu-Lian Ju ¹, Xiao-Jiao Zheng ¹, Xun Zhang ¹, Ting Xiao ¹, Christophe Pannecouque ³, Ting-Ting Li ⁴, Shuang-Xi Gu ⁵

Affiliations

1 Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering & Pharmacy, Wuhan Institute of Technology, Wuhan 430205, China.
2 School of Chemistry and Environmental Engineering, Wuhan Institute of Technology, Wuhan 430205, China. Electronic address: yyzhu531@163.com.
3 KU Leuven, Department of Microbiology and Immunology, Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, B-3000 Leuven, Belgium. Electronic address: christophe.pannecouque@kuleuven.be.
4 Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China.
5 Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering & Pharmacy, Wuhan Institute of Technology, Wuhan 430205, China. Electronic address: shuangxigu@163.com.

PMID: 28314514 DOI: 10.1016/j.bmc.2017.03.009

Abstract

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 5.8nM 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.

Keywords

AIDS; Anti-HIV; Diarylpyrimidines; Nonnucleoside reverse transcriptase inhibitors; SAR.

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