Arylazolylthioacetanilide. Part 11: design, synthesis and biological evaluation of 1,2,4-triazole thioacetanilide derivatives as novel non-nucleoside HIV-1 reverse transcriptase inhibitors

Med Chem. 2013 Nov;9(7):968-73. doi: 10.2174/1573406411309070010.

Abstract

A series of novel 1,2,4-triazole thioacetanilide derivatives has been designed, synthesized and evaluated for their anti-HIV activities in MT-4 cells. Half of these compounds showed moderate to potent activities against wild-type HIV-1 with an EC50 ranging from 38.0 μM to 4.08 µM. Among them, 2-(4-(2-fluorobenzyl)-5-isopropyl-4H-1,2,4-triazol- 3-ylthio)-N-(2-nitrophenyl)acetamide 7d was identified as the most promising compound (EC50 = 4.26 µM, SI = 49). However, no compound was active against HIV-2. The preliminary structure-activity relationships among the newly synthesized congeners are discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetanilides / chemical synthesis*
  • Acetanilides / chemistry
  • Acetanilides / pharmacology*
  • Anti-HIV Agents* / chemical synthesis
  • Anti-HIV Agents* / pharmacology
  • Cells, Cultured
  • Drug Design
  • Enzyme Activation / drug effects
  • Humans
  • Inhibitory Concentration 50
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Reverse Transcriptase Inhibitors / chemical synthesis*
  • Reverse Transcriptase Inhibitors / chemistry
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Structure-Activity Relationship
  • Triazoles / chemical synthesis*
  • Triazoles / chemistry
  • Triazoles / pharmacology

Substances

  • Acetanilides
  • Anti-HIV Agents
  • Reverse Transcriptase Inhibitors
  • Triazoles
  • 1,2,4-triazole
  • thioacetanilide