Novel 4(3H)-quinazolinone analogs: synthesis and 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-phe...

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Published inMedicinal chemistry research Vol. 22; no. 6; pp. 2815 - 2827
Main Authors 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.
Format Journal Article
LanguageEnglish
Published New York Springer-Verlag 01.06.2013
Subjects
Biochemistry
Biomedical and Life Sciences
Biomedicine
Cell Biology
Original Research
Pharmacology/Toxicology
Anticonvulsant activity
Quinazolinones
Synthesis
4
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Summary: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-3 H -quinazolin-2-yl)-thio]acetamide ( 12 ) representing the moderate active compounds and 2-[6-iodo-4-oxo-2-(thiophen-2-yl)-quinazolin-3(4 H )-yl]-isoindoline-1,3-dione ( 38 ) representing the remarkably active compounds in this stud, showed ED 50 values of 457 and 251 mg/kg; TD 50 values of 562 and 447 mg/kg; PI values of 1.22 and 1.78, LD 50 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.
ISSN:1054-2523
1554-8120
DOI:10.1007/s00044-012-0280-y