Synthesis and pharmacological evaluation of some N3-aryl/heteroaryl-substituted 2-(2-chlorostyryl)-6,7-dimethoxy-quinazolin-4(3H)-ones as potential anticonvulsant agents

Abstract

Certain novel 3-aryl/heteroaryl-substituted 2-(2-chlorostyryl)-6,7-dimethoxy-quinazolin-4(3H)-one (5a-5l) derivatives have been synthesized and evaluated for their anticonvulsant activity against maximal electroshock (MES)-, subcutaneous pentylenetetrazole (scPTZ)- and intracerebroventricular (icv) AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)-induced seizures in mice. The acute neurotoxicity was determined using the rotarod test, and hepatotoxicity was also assessed by estimating the AST (alanine aminotransferase) and ALT (alanine aminotransferase) enzyme activity. Among all the synthesized compounds, 5g showed the most significant anticonvulsant activity against MES (ED50: 41.3 μmol/kg)-, scPTZ (ED50: 82.5 μmol/kg)- and AMPA (ED50: 50.3 μmol/kg)-induced seizures with a protective index of 5.1. © 2014 Springer Science+Business Media New York.