Design, synthesis and pharmacological evaluation of N3 aryl/ heteroaryl substituted 2-((benzyloxy and phenylthio) methyl) 6,7- dimethoxyquinazolin-4(3H)-ones as potential anticonvulsant agents

• Published in: Medicinal chemistry (Shp-sariqah, United Arab Emirates) Vol. 10; no. 8; p. 800
• Main Authors: Das, Nirupam, Banerjee, Anupam G, Shrivastava, Sushant K
• Format: Journal Article
• Language: English
• Published: Netherlands 01.01.2014
• Subjects: Alanine Transaminase - blood; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid - administration & dosage; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid - adverse effects; Animals; Anticonvulsants - chemical synthesis; Anticonvulsants - chemistry; Anticonvulsants - pharmacology; Aspartate Aminotransferases - blood; Convulsants - administration & dosage; Disease Models, Animal; Drug Design; Drug Evaluation, Preclinical; Electroshock; Female; Injections, Intraventricular; Injections, Subcutaneous; Liver - drug effects; Liver - pathology; Male; Mice; Motor Activity - drug effects; Pentylenetetrazole - administration & dosage; Quinazolinones - chemical synthesis; Quinazolinones - chemistry; Quinazolinones - pharmacology; Rats; Rotarod Performance Test; Seizures - blood; Seizures - chemically induced; Seizures - drug therapy; Seizures - physiopathology; Structure-Activity Relationship
• ISSN: 1875-6638
• DOI: 10.2174/1573406410666140402152044

Novel N3 aryl/heteroaryl substituted 2-((benzyloxy and phenylthio) methyl) 6,7-dimethoxyquinazolin-4(3H)- ones (8a-8l) were synthesized and evaluated for their anticonvulsant activity using various models of epilepsy, such as maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ) and intracerebroventricular AMPA (α-amino-3- hydroxy-5-methyl-4-isoxazolepropionic acid)-induced seizures in mice. The rotarod test has been used to determine the acute neurotoxicity. Further, the serum enzymatic activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were assessed along with histopathological examination of liver. Among all the derivatives, compound 8f displayed significant activity profile based on the overall magnitude of activity and minimum neurotoxicity.