Synthesis of novel 4-substituted-7-trifluoromethylquinoline derivatives with nitric oxide releasing properties and their evaluation as analgesic and anti-inflammatory agents

Bioorg Med Chem. 2005 Oct 15;13(20):5759-65. doi: 10.1016/j.bmc.2005.05.053.

Abstract

Six derivatives of the general formula 2- or 4-(7-trifluoromethylquinolin-4-ylamino) benzoic acid N'-(nitrooxyacetyl or propionyl) hydrazide and an oxime of the formula 1-[4-(7-trifluoromethylquinolin-4-ylamino)phenyl]ethanone oxime were synthesized and tested for their in vivo anti-inflammatory, analgesic, and ulcerogenic properties, as well as their in vitro nitric oxide release ability. Compound 2-(7-trifluoromethylquinolin-4-ylamino)benzoic acid N'-(2-nitrooxy propionyl)hydrazide 12 showed an anti-inflammatory activity comparable to that of indomethacin in the carrageenan-induced rat paw edema test, and equipotency to glafenine in the acetic acid mice induced writhing model at 100mg/kg p.o., respectively. All the final compounds showed no tendency to induce stomach ulceration in rats; nitric oxide seems to contribute to their excellent safety profile.

MeSH terms

  • Analgesics / chemical synthesis*
  • Analgesics / pharmacology*
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis*
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Drug Evaluation, Preclinical
  • Female
  • Magnetic Resonance Spectroscopy
  • Male
  • Mice
  • Nitric Oxide / metabolism*
  • Quinolines / chemical synthesis*
  • Quinolines / pharmacology*
  • Rats
  • Spectrophotometry, Infrared

Substances

  • Analgesics
  • Anti-Inflammatory Agents, Non-Steroidal
  • Quinolines
  • Nitric Oxide