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

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.