Synthesis and pharmacological investigation of 5-substituted-3-methylsulfanyl-1H-pyrazole-4-carboxylic acid ethyl esters as new analgesic and anti-inflammatory agents

Arzneimittelforschung. 2012 Oct;62(10):457-62. doi: 10.1055/s-0032-1321830. Epub 2012 Aug 29.

Abstract

Purpose: To synthesize a new series of 5-substituted-3-methylsulfanyl-1H-pyrazole-4-carboxylic acid ethyl esters for their analgesic and anti-inflammatory activity.

Methods: The title compound synthesized by reacting the amino group of 5-amino-3-methylsulfanyl-1H-pyrazole-4-carboxylic acid ethyl ester with acid anhydrides, acid chlorides and phenyl dithiocarbamates. The synthesized compounds were characterized by IR, 1H-NMR and mass spectral data; the purity of the compounds was determined by elemental analysis. The title compounds were investigated for analgesic, anti-inflammatory and ulcerogenic behaviour.

Results: The compound 5-benzoylamino-3-methylsulfanyl-1-phenyl-1H-pyrazole-4-carboxylic acid ethyl ester (4c) emerged as the most active compound and exhibiting imperative analgesic and anti-inflammatory activities. Interestingly the test compounds showed only mild ulcerogenic potential when compared to indomethacin.

Conclusion: The compound (4c) could serve as a lead molecule for further modification to obtain a clinically useful novel class of analgesic and anti-inflammatory agents.

MeSH terms

  • Analgesics / adverse effects
  • Analgesics / chemical synthesis*
  • Analgesics / pharmacology
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis*
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Carrageenan
  • Female
  • Gastric Juice / metabolism
  • Indicators and Reagents
  • Inflammation / chemically induced
  • Inflammation / drug therapy
  • Magnetic Resonance Spectroscopy
  • Male
  • Mice
  • Pain Measurement
  • Pyrazoles / adverse effects
  • Pyrazoles / chemical synthesis*
  • Pyrazoles / pharmacology
  • Rats
  • Reaction Time / drug effects
  • Stomach Ulcer / chemically induced
  • Stomach Ulcer / pathology
  • Sulfhydryl Compounds / adverse effects
  • Sulfhydryl Compounds / chemical synthesis*
  • Sulfhydryl Compounds / pharmacology

Substances

  • Analgesics
  • Anti-Inflammatory Agents, Non-Steroidal
  • Indicators and Reagents
  • Pyrazoles
  • Sulfhydryl Compounds
  • Carrageenan