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: [email protected].
  • 3. KU Leuven, Department of Microbiology and Immunology, Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, B-3000 Leuven, Belgium. Electronic address: [email protected].
  • 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: [email protected].
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.