Novel 4(3H)-quinazolinone analogs: synthesis and anticonvulsant activity

作者：El Azab Adel S; Abdel Hamide Sami G; Sayed Ahmed Mohamed M; Hassan Ghada S; El Hadiyah Tariq M; Al Shabanah Othman A; Al Deeb Omar A; El Subbagh Hussein I^*

来源：Medicinal Chemistry Research, 2013, 22(6): 2815-2827.

DOI：10.1007/s00044-012-0280-y

• Synthesis
• 4(3H)-Quinazolinones
• Anticonvulsant activity

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 GABA(A) 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.

• 出版日期2013-6