Discovery of novel 2-(3-(2-chlorophenyl)pyrazin-2-ylthio)-N-arylacetamides as potent HIV-1 inhibitors using a structure-based bioisosterism approach

Bioorg Med Chem. 2012 Dec 1;20(23):6795-802. doi: 10.1016/j.bmc.2012.09.058. Epub 2012 Oct 6.


The present work is an extension of our ongoing efforts towards the development and identification of new molecules with anti-HIV activity which have previously led to the discovery of arylazolylthioacetanilides as highly active NNRTIs. In this article, a series of 2-2-(3-(2-chlorophenyl)pyrazin-2-ylthio)-N-arylacetamide derivatives were synthesized and evaluated for in vitro anti-HIV activity. Most of the tested compounds exhibited moderate activities against wild-type HIV-1. Among them, compound 6k showed significant activity against wild-type HIV-1 with an EC(50) value of 1.7μM, along with moderate activity against wild-type reverse transcriptase (RT). The preliminary structure-activity relationship (SAR) and docking calculations of this new series of compounds were also investigated, which may help designing more potent molecules.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / chemical synthesis
  • Anti-HIV Agents / chemistry*
  • Anti-HIV Agents / pharmacology*
  • Drug Design
  • HIV Infections / drug therapy*
  • HIV Reverse Transcriptase / antagonists & inhibitors*
  • HIV Reverse Transcriptase / metabolism
  • HIV-1 / drug effects*
  • HIV-1 / enzymology
  • Humans
  • Models, Molecular
  • Structure-Activity Relationship
  • Thioacetamide / chemical synthesis
  • Thioacetamide / chemistry*
  • Thioacetamide / pharmacology*


  • Anti-HIV Agents
  • Thioacetamide
  • HIV Reverse Transcriptase