Synthesis and anti-inflammatory activity of polyazaheterocyclic derivatives of 6-amino-2,4-lutidine and their precursors

Arzneimittelforschung. 1997 May;47(5):635-42.

Abstract

Derivatives of N-(4,6-pyridin-2-yl)arylcarboxamides resulting from the integration of the amidic function into 4H-1,2,4-triazole, triazol-3(2H)-one and 1H-tetrazole rings were evaluated as potential anti-inflammatory compounds. The level of activity decreased as compared to carboxamides, nevertheless their precursors and notably the corresponding amidrazones exhibited potent activity; amidrazone 21, whose ID50 was 34.4 mg.kg-1 in the rat paw edema test, was selected for further investigation. These heteroarylcarboxamide derivatives could represent an interesting alternative to classical non-steroidal anti-inflammatories in so far as they partly act by inhibition of tumor necrosis factor-alpha production.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Anti-Inflammatory Agents, Non-Steroidal / toxicity
  • Carrageenan
  • Edema / chemically induced
  • Edema / drug therapy
  • Lethal Dose 50
  • Male
  • Pyridines / chemical synthesis*
  • Pyridines / therapeutic use
  • Pyridines / toxicity
  • Rats
  • Rats, Wistar
  • Tetrazoles / chemical synthesis*
  • Tetrazoles / therapeutic use
  • Tetrazoles / toxicity
  • Triazoles / chemical synthesis*
  • Triazoles / therapeutic use
  • Triazoles / toxicity

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Pyridines
  • Tetrazoles
  • Triazoles
  • 2,4-dimethylpyridine
  • Carrageenan