1,2,3-Thiadiazole thioacetanilides as a novel class of potent HIV-1 non-nucleoside reverse transcriptase inhibitors

Bioorg Med Chem Lett. 2008 Oct 15;18(20):5368-71. doi: 10.1016/j.bmcl.2008.09.055. Epub 2008 Sep 18.


A novel series of 1,2,3-thiadiazole thioacetanilide (TTA) derivatives have been designed, synthesized and evaluated for its anti-HIV activities in MT-4 cells. Some derivatives proved to be highly effective in inhibiting HIV-1 replication at nanomolar concentrations. Among them, 2-[4-(2,4-dichlorophenyl)-1,2,3-thiadiazol-5-ylthio]-N-(2-nitrophenyl)acetamide 7d2 was identified as the most promising compound (EC(50)=0.059+/-0.02 microM, CC(50)>283.25 microM, SI>4883). The structure-activity relationship (SAR) of these novel structural congeners is discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / chemical synthesis*
  • Anti-HIV Agents / pharmacology
  • Biological Assay
  • Cell Line
  • Chemistry, Pharmaceutical / methods*
  • Drug Design
  • Drug Evaluation, Preclinical
  • HIV Infections / drug therapy*
  • HIV Reverse Transcriptase / antagonists & inhibitors
  • HIV-1 / metabolism
  • Humans
  • Models, Chemical
  • Reverse Transcriptase Inhibitors / chemical synthesis*
  • Reverse Transcriptase Inhibitors / pharmacology
  • Structure-Activity Relationship
  • Thiadiazoles / chemical synthesis*
  • Thiadiazoles / pharmacology
  • Virus Replication


  • Anti-HIV Agents
  • Reverse Transcriptase Inhibitors
  • Thiadiazoles
  • HIV Reverse Transcriptase