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

被引：14
作者：
Das, Nirupam [1 ]
Garabadu, Debapriya [2 ]
Banerjee, Anupam G. [1 ]
Krishnamurthy, Sairam [2 ]
Shrivastava, Sushant K. [1 ]
机构：
[1] Indian Inst Technol BHU, Dept Pharmaceut, Pharmaceut Chem Res Lab, Varanasi 221005, Uttar Pradesh, India
[2] Indian Inst Technol BHU, Dept Pharmaceut, Neurotherapeut Lab, Varanasi 221005, Uttar Pradesh, India
来源：
MEDICINAL CHEMISTRY RESEARCH | 2014年 / 23卷 / 09期
关键词：
Quinazolin-4(3H)-ones; Synthesis; Anticonvulsant activity; AMPA-induced seizure; RECEPTOR; DESIGN; 2,3-BENZODIAZEPINE; DERIVATIVES; ANTAGONIST; SEIZURE;
D O I：
10.1007/s00044-014-0990-4
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
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 (alpha-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 mu mol/kg)-, scPTZ (ED50: 82.5 mu mol/kg)- and AMPA (ED50: 50.3 mu mol/kg)-induced seizures with a protective index of 5.1.
引用
收藏
页码：4167 / 4176
页数：10
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