2. Academic Validation
  3. A novel family of diarylpyrimidines (DAPYs) featuring a diatomic linker: Design, synthesis and anti-HIV activities

A novel family of diarylpyrimidines (DAPYs) featuring a diatomic linker: Design, synthesis and anti-HIV activities

  • Bioorg Med Chem. 2015 Oct 15;23(20):6587-93. doi: 10.1016/j.bmc.2015.09.020.
Shuang-Xi Gu 1,  Heng Qiao 2,  Yuan-Yuan Zhu 3,  Qi-Chao Shu 2,  Hui Liu 2,  Xiu-Lian Ju 4,  Erik De Clercq 5,  Jan Balzarini 5,  Christophe Pannecouque 5
Affiliations

Affiliations

  • 1 Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Wuhan 430073, China. Electronic address: shuangxigu@163.com.
  • 2 Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Wuhan 430073, China.
  • 3 School of Chemistry & Environmental Engineering, Wuhan Institute of Technology, Wuhan 430073, China.
  • 4 Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Wuhan 430073, China. Electronic address: xiulianju2008@aliyun.com.
  • 5 KU Leuven, Department of Microbiology and Immunology, Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, B-3000 Leuven, Belgium.
PMID: 26385446 DOI: 10.1016/j.bmc.2015.09.020
Abstract

To improve the conformational flexibility and positional adaptability of the traditional diarylpyrimidines (DAPYs), a family of diarylpyrimidines featuring a C-N diatomic linker between the left wing benzene ring and the central pyrimidine was firstly designed, synthesized, and evaluated for in vitro anti-HIV activity. Most of target molecules showed excellent activities against wild-type (WT) HIV-1. Among them the most potent two compounds 12h and 12r displayed extremely potent WT HIV-1 inhibitory activities with an EC50 of 2.6 nM and 3.0 nM, respectively, while their selective index (CC50/EC50) values were both over 1000. Another compound 12b (EC50 14.9 nM) was also noteworthy due to its high SI of 18,614. Moreover, all of compounds were evaluated for their WT HIV-1 Reverse Transcriptase activities, which shown that the newly synthesized CH2NH-DAPYs bind to HIV-1 RT and belong to the genuine NNRTIs. However, the synthesized compounds lack the activities against HIV-1 double mutant (RES056) and HIV-2 (ROD). Thus it is an upcoming objective to improve the activities against HIV-1 double mutants.

Keywords

Anti-HIV activities; Diarylpyrimidines; HIV-1 reverse transcriptase inhibitors.

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