1. Academic Validation
  2. Synthesis and structure-activity relationship of novel diarylpyrimidines with hydromethyl linker (CH(OH)-DAPYs) as HIV-1 NNRTIs

Synthesis and structure-activity relationship of novel diarylpyrimidines with hydromethyl linker (CH(OH)-DAPYs) as HIV-1 NNRTIs

  • Bioorg Med Chem. 2011 Sep 1;19(17):5117-24. doi: 10.1016/j.bmc.2011.07.023.
Shuang-Xi Gu 1 Qiu-Qin He Shi-Qiong Yang Xiao-Dong Ma Fen-Er Chen Erik De Clercq Jan Balzarini Christophe Pannecouque
Affiliations

Affiliation

  • 1 Department of Chemistry, Fudan University, Shanghai, People's Republic of China.
Abstract

A series of 26 diarylpyrimidines, characterized by the hydroxymethyl linker between the left wing benzene ring and the central pyrimidine, were synthesized and evaluated for in vitro anti-HIV activity. Most of the compounds exhibited moderate to excellent activities against wild-type HIV-1. Among them, compound 10i, bearing a chlorine atom at the C-2 position of left benzene ring, was the best congener and showed potent activity against wild-type HIV-1 with an EC(50) value of 0.009 μM, along with moderate activities against the double RT mutant (K103N+Y181C) HIV-1(III(B)) and HIV-2(ROD) with an EC(50) value of 6.2 and 6.0 μM, respectively. The preliminary structure-activity relationship (SAR) of this new series of compounds was also investigated.

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