Synthesis and anti-HIV activity evaluation of 2-(4-(naphthalen-2-yl)-1,2,3-thiadiazol-5-ylthio)-N-acetamides as novel non-nucleoside HIV-1 reverse transcriptase inhibitors

Eur J Med Chem. 2009 Nov;44(11):4648-53. doi: 10.1016/j.ejmech.2009.06.037. Epub 2009 Jul 4.


A series of 2-(4-(naphthalen-2-yl)-1,2,3-thiadiazol-5-ylthio)acetamide (TTA) derivatives were synthesized and evaluated as potent inhibitors of HIV-1. Among the newly disclosed TTAs, compounds 7f, 7 g and 7c were the most potent inhibitors of HIV-1 replication of the series (EC(50)=0.17+/-0.02, 0.36+/-0.19 and 0.39+/-0.05 microM, respectively), coupled with a reasonable selectivity index (SI>1452, >845, and >774, respectively). They possess improved or similar HIV-1 inhibitory activity compared with NVP (EC(50)=0.208 microM) and DLV (EC(50)=0.320 microM). The preliminary structure-activity relationships among the newly synthesized congeners are discussed briefly and rationalized by docking studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetamides / chemical synthesis
  • Acetamides / chemistry*
  • Acetamides / pharmacology*
  • Anti-HIV Agents / chemical synthesis
  • Anti-HIV Agents / chemistry*
  • Anti-HIV Agents / pharmacology*
  • Cell Line
  • HIV Infections / drug therapy*
  • HIV Reverse Transcriptase / antagonists & inhibitors*
  • HIV Reverse Transcriptase / chemistry
  • HIV Reverse Transcriptase / metabolism
  • HIV-1 / drug effects*
  • HIV-2 / drug effects
  • Humans
  • Models, Molecular
  • Protein Binding
  • Structure-Activity Relationship


  • Acetamides
  • Anti-HIV Agents
  • reverse transcriptase, Human immunodeficiency virus 1
  • HIV Reverse Transcriptase