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. Epub 2017 Mar 6.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / pharmacology*
  • Carbon-13 Magnetic Resonance Spectroscopy
  • HIV-1 / drug effects*
  • Molecular Docking Simulation
  • Proton Magnetic Resonance Spectroscopy
  • Pyrimidines / chemistry*
  • Pyrimidines / pharmacology*
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Spectrometry, Mass, Electrospray Ionization

Substances

  • Anti-HIV Agents
  • Pyrimidines
  • Reverse Transcriptase Inhibitors