1-phenyl-1H-pyrazole derivatives with antiinflammatory, analgesic and antipiretic activities

Farmaco. 1990 Feb;45(2):167-86.

Abstract

Reaction of ethyl or methyl 2-dimethylaminomethylene-3-oxoalkanoates 2 with phenylhydrazine gave the corresponding esters of 5-substituted 1-phenyl-1H-pyrazole-4-carboxylic acids 3 in high yields. Esters 3 were hydrolyzed to the relative carboxylic acids 4, which were converted by heating to 5-substituted 1-phenyl-1H-pyrazoles 5 in excellent yields. Reaction of methyl 5,5-dimethyl-3-dimethylaminomethylene-2,4-dioxohexanoate with phenylhydrazine afforded methyl 1-phenyl-4-pivaloyl-1H-pyrazole-5-carboxylate 8 b, which was converted as above to the corresponding carboxylic acid 10 b and this to 1-phenyl-4-pivaloyl-1H-pyrazole 11 b. Starting from 5-methoxymethyl-1-phenyl-1H-pyrazole, 1-phenyl-1H-pyrazole-5-acetic acid 18 and its alpha-methyl derivative 19 were also synthesized. Compounds 18, 19, 10 b and 11 b showed a strong antiinflammatory activity in rats; the same compounds in general as well as 8 b, showed appreciable analgesic and antipyretic activities in mice and rats, respectively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis*
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Carrageenan
  • Edema / chemically induced
  • Edema / drug therapy
  • Edema / pathology
  • Fever / chemically induced
  • Fever / prevention & control
  • Foot / pathology
  • Mice
  • Pain Measurement
  • Pyrazoles / chemical synthesis*
  • Pyrazoles / pharmacology
  • Rats
  • Reaction Time / drug effects
  • Yeast, Dried

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Pyrazoles
  • Carrageenan