Synthesis of carboxyalkylthio-triazoles and bicyclic derivatives with antiinflammatory and analgesic activity

Farmaco. 1992 Feb;47(2):149-69.

Abstract

3-Carboxyalkylthio derivatives of 5-alkoxyphenyl-1,2,4-triazole were prepared, performing some substitutions both on carboxyalkyl chain, by lengthening it or introducing substituents with increasing molecular weight in alpha- at the carboxy group, and on N-4 atom in the triazole ring, by introducing an amino or methyl group, so that to vary steric conformation along with the lipophilicity of molecules. The corresponding bicyclic thiazolo-triazolone and triazolo-thiazinone derivatives, which represent the rigid models of carboxymethylthio- and carboxyethylthio- open structures, were also obtained. All the compounds show "in vivo" antiinflammatory activity, while only carboxyalkylthio derivatives of 4-amino- and 4-methyltriazole display an appreciable analgesic one. From the relief of some data on substituent present in the synthesized compounds, a structure-activity relationship is also suggested.

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
  • Anti-Inflammatory Agents, Non-Steroidal / toxicity
  • Behavior, Animal / drug effects
  • Carrageenan
  • Edema / chemically induced
  • Edema / drug therapy
  • Lethal Dose 50
  • Mice
  • Pain Measurement
  • Rats
  • Structure-Activity Relationship
  • Superoxides / metabolism
  • Thiazoles / chemical synthesis*
  • Thiazoles / pharmacology
  • Thiazoles / toxicity
  • Triazoles / chemical synthesis*
  • Triazoles / pharmacology
  • Triazoles / toxicity

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Thiazoles
  • Triazoles
  • Superoxides
  • Carrageenan