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

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

Volume: 14 Issue: 4

Author(s): Ameen A. Abu-Hashem*Mohamed El-Shazly

Affiliation:

• Photochemistry Department (Heterocyclic Unit), National Research Centre, 12622 Dokki, Giza,Egypt

Keywords: Analgesic activity, anti-inflammatory, isoxazole, pyrazine, pyridazine, pyrimidine.

Abstract: 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 material.

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.

Cite this article as:

Abu-Hashem A. Ameen *, El-Shazly Mohamed , Synthesis of New Isoxazole-, Pyridazine-, Pyrimidopyrazines and Their Anti-Inflammatory and Analgesic Activity, Medicinal Chemistry 2018; 14 (4) . https://dx.doi.org/10.2174/1573406414666180112110947