Background: Isoxazoles, pyridazines, and pyrimidopyrazines have recently attracted
attention 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 pyrimidopyrazines
through efficient high yield protocol for evaluating their analgesics and anti-inflammatory activities.
Method: A series of novel isoxazole-, pyridazine-, pyrimidopyrazine derivatives was prepared
from 5,8-alkyl-1,3-dimethyl-5,6-dihydropyrimido[5,6-e]pyrazine-2,4,7-trione (1a,b) as the starting
Results: The prepared derivatives were synthesized in moderate to good yields (60-75%) in a
stepwise efficient protocol under mild condition. These new compounds have been proven by several
spectroscopic techniques as IR, 1D and 2D NMR techniques and mass analysis. The in vivo
anti-inflammatory was assessed for the synthesized compounds using carrageenan-induced rat hind
paw edema model. Also, the in vivo analgesic activity for these products was examined utilizing
hot-plate and acetic acid-induced writhing response assays.
Conclusion: The isoxazole derivatives (3a-f) showed the most forceful anti-inflammatory and analgesic
activities. Pyrimidopyrazines (4a-f) demonstrated weaker but comparable antiinflammatory
and analgesic activities to the positive controls.