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Novel 4(3H)-quinazolinone analogs: synthesis and anticonvulsant activity |
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| Authors: | Adel S. El-Azab Sami G. Abdel-Hamide Mohamed M. Sayed-Ahmed Ghada S. Hassan Tariq M. El-Hadiyah Othman A. Al-Shabanah Omar A. Al-Deeb Hussein I. El-Subbagh |
| Affiliation: | 1. Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia 2. Department of Organic Chemistry, Faculty of Pharmacy, Al-Azhar University, Cairo, 11884, Egypt 3. Department of Pharmaceutical Chemistry, College of Pharmacy, Salman Bin Abdulaziz University, Alkharj, Saudi Arabia 4. Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia 5. Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt 6. Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences & Pharmaceutical Industries, Future University, Cairo, 12311, Egypt |
| 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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