Synthesis of New Isoxazole-, Pyridazine-, Pyrimidopyrazines and Their Anti-Inflammatory and Analgesic Activity

摘要

Background: Isoxazoles, pyridazines, and pyrimidopyrazines have recently attractedattention due to their potent pharmacological activities. They exhibited anticancer, neuroprotective,analgesic and anti-inflammatory effects.Objective: The study aimed to synthesize novel isoxazoles, pyridazines, and pyrimidopyrazinesthrough efficient high yield protocol for evaluating their analgesics and anti-inflammatory activities.Method: A series of novel isoxazole-, pyridazine-, pyrimidopyrazine derivatives was preparedfrom 5,8-alkyl-1,3-dimethyl-5,6-dihydropyrimido[5,6-e]pyrazine-2,4,7-trione (1a,b) as the startingmaterial.Results: The prepared derivatives were synthesized in moderate to good yields (60-75%) in astepwise efficient protocol under mild condition. These new compounds have been proven by severalspectroscopic techniques as IR, 1D and 2D NMR techniques and mass analysis. The in vivoanti-inflammatory was assessed for the synthesized compounds using carrageenan-induced rat hindpaw edema model. Also, the in vivo analgesic activity for these products was examined utilizinghot-plate and acetic acid-induced writhing response assays.Conclusion: The isoxazole derivatives (3a-f) showed the most forceful anti-inflammatory and analgesicactivities. Pyrimidopyrazines (4a-f) demonstrated weaker but comparable antiinflammatoryand analgesic activities to the positive controls.