Antirheumatic activity of 3-imidazole-substituted-4,5-diaryloisoxazol-3-carboxylic acid amide derivative, a proteinase inhibitor-activated type II receptor

Treatment of rheumatoid arthritis is a complex and time-consuming process that does not always lead to significant results both due to poor effectiveness of drugs and drug toxicity. It means we need to search for new pharmacological targets to influence the pathological process, one of which is inhibition of proteinase-activated receptors 2 (PAR2 receptors) activity. In 2016–2019, synthesis of low-molecular-weight antagonists of PAR2 receptors belonging to 4,5-dihydroisoxazole-5-carboxamide derivatives was carried out, and in 2023 their anti-inflammatory efficacy was examined using the formaldehyde edema model. The most effective laboratory R004 compound was tested on a model of autoimmune pristane-induced inflammation in rats. During treatment of chronic inflammation in rats, R004 inhibited significant development of edema of feet, damage to small joints, and specific changes in the formula of white blood, and according to biochemical blood test led to normalization of liver and kidney functions and energy metabolism. R004 turned out to be more effective and safer than the comparator drugs such as diclofenac sodium and dexamethasone.