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

Publication date: Available online 6 March 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Huan-Huan Lu, Ping Xue, Yuan-Yuan Zhu, Xiu-Lian Ju, Xiao-Jiao Zheng, Xun Zhang, Ting Xiao, Christophe Pannecouque, Ting-Ting Li, Shuang-Xi Gu
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.

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