Abstract
A new series of 4-acetyl-1-substituted-3,4-dihydroquinoxalin-2(1H)-ones (2–13) were designed and synthesized in order to evaluate their AMPA-receptor antagonism as a potential mode of anticonvulsant activity. The structure of the synthesized compounds was confirmed by elemental analysis and spectral data (IR, 1HNMR, 13CNMR and Mass). The molecular design was performed for all the synthesized compounds to predict their binding affinity to AMPA-receptor in order to rationalize their anticonvulsant activity in a qualitative way. The data obtained from the molecular modeling was strongly correlated with that obtained from the biological screening which revealed that; compounds 12b, 13, 12a and 7a showed the highest binding affinities toward AMPA-receptor and also showed the highest anticonvulsant activities against pentylenetetrazole -induced seizures in experimental mice. The relative potencies of these compounds were 1.66, 1.66, 1.61 and 0.82 respectively, in comparing to diazepam.
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Acknowledgments
The authors extend their appreciation and thanking to Prof. Dr. Ahmed M. Mansour, Pharmacology & Toxicology Department, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt for helping in the pharmacological screening.
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El-Helby, AG.A., Ayyad, R.R.A., El-Adl, K. et al. Design, molecular docking and synthesis of some novel 4-acetyl-1-substituted-3,4-dihydroquinoxalin-2(1H)-one derivatives for anticonvulsant evaluation as AMPA-receptor antagonists. Med Chem Res 25, 3030–3046 (2016). https://doi.org/10.1007/s00044-016-1723-7
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DOI: https://doi.org/10.1007/s00044-016-1723-7