Synthesis, anti-allergic rhinitis evaluation and mechanism investigation of novel 1,2,4-triazole-enamides as CB1 R antagonist

Eur J Med Chem. 2025 May 5:289:117461. doi: 10.1016/j.ejmech.2025.117461. Epub 2025 Feb 27.

Abstract

Allergic rhinitis (AR) is a non-infectious inflammatory disease and affects nearly half of the world's population currently, thus becoming a global health problem. In our study, a series of 1,2,4-triazole enamides were designed and used to evaluate the anti-inflammatory activity of AR. We found that compound 11g could significantly reduce the increased expression of interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in Raw264.7 cells induced by lipopolysaccharides (LPS), and inhibit the expression of inflammation through MAPK pathway and NF-κB pathway by influencing the expression of cannabinoid-1 receptor (CB1 R). In the AR mice model, 11g can significantly reduce the number of inflammatory cells in Nasal lavage fluids (NLF), showing a good effect on the treatment of AR. This study provides a new and effective candidate for treatment of AR.

Keywords: 1,2,4-Triazole-enamides; Allergic rhinitis; Anti-inflammation; CB1 receptor; MAPK; NF-κB.

MeSH terms

  • Amides* / chemical synthesis
  • Amides* / chemistry
  • Amides* / pharmacology
  • Animals
  • Anti-Allergic Agents / chemical synthesis
  • Anti-Allergic Agents / chemistry
  • Anti-Allergic Agents / pharmacology
  • Dose-Response Relationship, Drug
  • Lipopolysaccharides* / antagonists & inhibitors
  • Lipopolysaccharides* / pharmacology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Molecular Structure
  • RAW 264.7 Cells
  • Receptor, Cannabinoid, CB1* / antagonists & inhibitors
  • Receptor, Cannabinoid, CB1* / metabolism
  • Rhinitis, Allergic* / drug therapy
  • Structure-Activity Relationship
  • Triazoles* / chemical synthesis
  • Triazoles* / chemistry
  • Triazoles* / pharmacology

Substances

  • Triazoles
  • Receptor, Cannabinoid, CB1
  • 1,2,4-triazole
  • Lipopolysaccharides
  • Amides
  • Anti-Allergic Agents