Synthesis and biological evaluation of pyridazine derivatives as novel HIV-1 NNRTIs

Bioorg Med Chem. 2013 Apr 1;21(7):2128-34. doi: 10.1016/j.bmc.2012.12.049. Epub 2013 Jan 9.


In continuation of our efforts toward identification and optimization of novel non-nucleoside reverse transcriptase inhibitors (NNRTIs), we have employed a structure-based bioisosterism strategy, with which a new series of diarylpyridazine (DAPD) derivatives were synthesized and evaluated for their anti-HIV-1 (human immunodeficiency virus type 1) activity. Most of the title compounds displayed excellent anti-HIV-1 activity at submicromolar concentrations ranging from 34 nM to 5.08 μM. The most promising compound 8g inhibited HIV-1 IIIB in MT-4 cells at a low EC50 value (0.034 μM), which was lower than the reference drug nevirapine and delavirdine. The structure activity relationships (SARs) were discussed and rationalized by docking simulations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Delavirdine / pharmacology
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV Reverse Transcriptase / antagonists & inhibitors*
  • HIV Reverse Transcriptase / metabolism
  • HIV-1 / drug effects*
  • HIV-1 / enzymology
  • Humans
  • Nevirapine / pharmacology
  • Pyridazines / chemical synthesis
  • Pyridazines / chemistry*
  • Pyridazines / pharmacology*
  • Reverse Transcriptase Inhibitors / chemical synthesis
  • Reverse Transcriptase Inhibitors / chemistry*
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Structure-Activity Relationship


  • Pyridazines
  • Reverse Transcriptase Inhibitors
  • Nevirapine
  • Delavirdine
  • HIV Reverse Transcriptase