1-Aryl-1H-pyrazole-5-acetic acids with antiinflammatory, analgesic and other activities

Farmaco. 1994 Feb;49(2):115-9.

Abstract

Reaction of methyl 4-methoxy-2-dimethylaminomethylene-3-oxobutanoate with arylhydrazines gave methyl 1-aryl-5-(methoxymethyl)-1H-pyrazole-4-carboxylates 1 in high yields. Esters 1 were hydrolyzed to the relative carboxylic acids, which were converted by heating to 1-aryl-5-(methoxymethyl)-1H-pyrazoles 3 in good yields. Reaction of 3 with hydrobromic acid afforded the intermediate 1-aryl-5-(bromomethyl)-1H-pyrazoles, which were converted with potassium cyanide to 1-aryl-1H-pyrazole-5- acetonitriles, whose hydrolysis gave the required 1-aryl-1H-pyrazole-5-acetic acids. Some acids 5 showed a strong antiinflammatory and analgesic activity in rats and mice, respectively, as well as moderate antipyretic and in vito platelet antiaggregating effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates / chemical synthesis*
  • Acetates / pharmacology
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis*
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Carrageenan
  • Collagen / antagonists & inhibitors
  • Collagen / pharmacology
  • Edema / chemically induced
  • Edema / prevention & control
  • Fever / chemically induced
  • Fever / prevention & control
  • Humans
  • In Vitro Techniques
  • Magnetic Resonance Spectroscopy
  • Mice
  • Pain Measurement / drug effects
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / chemical synthesis
  • Platelet Aggregation Inhibitors / pharmacology
  • Pyrazoles / chemical synthesis*
  • Pyrazoles / pharmacology
  • Rats
  • Spectrophotometry, Infrared

Substances

  • Acetates
  • Anti-Inflammatory Agents, Non-Steroidal
  • Platelet Aggregation Inhibitors
  • Pyrazoles
  • Carrageenan
  • Collagen