Design, synthesis, and biological evaluation of novel 3,5-disubstituted-1,2,6-thiadiazine-1,1-dione derivatives as HIV-1 NNRTIs

Chem Biol Drug Des. 2013 Oct;82(4):384-93. doi: 10.1111/cbdd.12160. Epub 2013 Sep 10.


On the basis of structural features, binding mode, and structure-activity relationship studies of two pyrimidine-derived non-nucleoside reverse-transcriptase inhibitors, DABOs, and diaryl pyrimidines, a novel class of 1,2,6-thiadiazine-1,1-dione derivatives were rationally designed using the strategies of bioisosterism and molecular hybridization, synthesized, and evaluated for their anti-HIV activity in MT4 cell cultures. Three compounds were found to have moderate activity against HIV-1 replication with EC50 values ranging from 23 to 32 μm. To further confirm the binding target, compound IIg was selected to conduct an HIV-1 reverse-transcriptase inhibitory assay. In addition, preliminary structure-activity relationship analysis among the newly synthesized compounds was discussed, and the binding mode of the active compound IIg was rationalized by molecular docking and physicochemical studies.

Keywords: 1,2,6-thiadiazine-1,1-dione; HIV-1; activity assay; non-nucleoside reverse-transcriptase inhibitors; reverse-transcriptase; synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Drug Design*
  • Drug Evaluation, Preclinical
  • HIV-1 / drug effects*
  • Humans
  • Magnetic Resonance Spectroscopy
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Reverse Transcriptase Inhibitors / chemistry
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Thiadiazines / pharmacology*


  • Reverse Transcriptase Inhibitors
  • Thiadiazines