Abstract
A new series of quinazoline analogs was designed, synthesized, and evaluated for their anticonvulsant activity. Compounds 6, 12, 21, 36, 37, and 38 showed 70–100 % protection against PTZ-induced seizures acting as GABAA receptor agonists. Compound N-(3,4,5,6-tetrachloro-phthalimido)-2-[(3-phenyl-4-oxo-6-methyl-3H-quinazolin-2-yl)-thio]acetamide (12) representing the moderate active compounds and 2-[6-iodo-4-oxo-2-(thiophen-2-yl)-quinazolin-3(4H)-yl]-isoindoline-1,3-dione (38) representing the remarkably active compounds in this stud, showed ED50 values of 457 and 251 mg/kg; TD50 values of 562 and 447 mg/kg; PI values of 1.22 and 1.78, LD50 values of 1,288 and 1,380 mg/kg, and TI values of 2.82 and 5.50, respectively. Compound 38 proved to be almost twofold more active than the standard drug sodium valproate.
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The financial support of King Abdulaziz City for Science and Technology, Grant AR-25-53, is greatly acknowledged.
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El-Azab, A.S., Abdel-Hamide, S.G., Sayed-Ahmed, M.M. et al. Novel 4(3H)-quinazolinone analogs: synthesis and anticonvulsant activity. Med Chem Res 22, 2815–2827 (2013). https://doi.org/10.1007/s00044-012-0280-y
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DOI: https://doi.org/10.1007/s00044-012-0280-y