Design, synthesis, computational and biological evaluation of some new hydrazino derivatives of DHA and pyranopyrazoles

Eur J Med Chem. 2012 Apr;50:81-9. doi: 10.1016/j.ejmech.2012.01.042. Epub 2012 Feb 1.


Two series of compounds namely, 4-aryl/heteroaryl hydrazino-3-acetyl-6-methyl-2H-pyran-2-ones (4a-4j) and pyrano[4,3-c]pyrazoles (6a-6e and 6g) were synthesized starting from 3-acetyl-4-chloro-6-methyl-2H-pyran-2-one (2). Estimation of pharmacotherapeutic potential, possible molecular mechanism of action, toxic/side effects and interaction with drug-metabolizing enzymes were made for the synthesized compounds on the basis of prediction of activity spectra for substances (PASS) prediction results and their analysis by PharmaExpert software. COX inhibition predicted by PASS was confirmed by experimental evaluation and validated via docking studies. Out of all the compounds, compounds 4h, 4j, 6e, 6g exhibited good anti-inflammatory activity, whereas compounds 4b, 4c, 4h, 4i, 4j, 6b, 6e, 6g showed excellent analgesic activity compared with standard drug Diclofenac sodium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetic Acid / toxicity
  • Analgesics / chemical synthesis*
  • Analgesics / pharmacology
  • Animals
  • Anti-Inflammatory Agents / chemical synthesis*
  • Anti-Inflammatory Agents / pharmacology
  • Carrageenan / toxicity
  • Computational Biology*
  • Cyclooxygenase Inhibitors / chemical synthesis
  • Cyclooxygenase Inhibitors / pharmacology
  • Diclofenac / pharmacology
  • Drug Design*
  • Edema / chemically induced
  • Edema / drug therapy
  • Indicators and Reagents / toxicity
  • Mice
  • Pain / chemically induced
  • Pain / drug therapy
  • Pyrazoles / chemistry*
  • Structure-Activity Relationship


  • Analgesics
  • Anti-Inflammatory Agents
  • Cyclooxygenase Inhibitors
  • Indicators and Reagents
  • Pyrazoles
  • Diclofenac
  • Carrageenan
  • Acetic Acid