Imidazolylchromanone oxime ethers as potential anticonvulsant agents: Anticonvulsive evaluation in PTZ-kindling model of epilepsy and SAR study.
Imidazolylchromanone oxime ethers as potential anticonvulsant agents: Anticonvulsive evaluation in PTZ-kindling model of epilepsy and SAR study.
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咪唑基色满酮肟醚作为潜在的抗惊厥剂：癫痫 PTZ 点火模型的抗惊厥评估和 SAR 研究。
DOI：
10.1016/j.bmcl.2010.12.021
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发表时间：
2011
影响因子：
2.7
通讯作者：
R. Khorasani
中科院分区：
文献类型：
--
作者：
S. Emami;A. Kebriaeezadeh;N. Ahangar;R. Khorasani
作为我们开发唑基苯并二氢吡喃酮衍生物作为潜在抗惊厥剂的努力的继续，我们探索了带有不同亲脂性O-苄基的咪唑基苯并二氢吡喃酮的（Z）-和（E）-肟醚衍生物，并在PTZ点燃癫痫模型中测试了它们的抗惊厥活性。O-（2，4-二氯苄基）肟8a、16 a和20 a在30 mg/kg剂量下对戊四氮点燃动物癫痫发作有明显的延迟作用。最有效的化合物是7-氯色满酮-O-（2，4-二氯苄基）肟8a和20 a。SAR研究表明，在苯并二氢吡喃环的7-位引入氯原子和/或在2-位引入甲基可提高O-（2，4-二氯苄基）肟系列化合物的抗癫痫活性。
As a continuation of our efforts to develop the azolylchromanone derivatives as potential anticonvulsant agents, we explored (Z)- and (E)-oxime ether derivatives of imidazolylchromanones bearing different lipophilic O-benzyl groups and tested their anticonvulsant activities in PTZ-kindling model of epilepsy. O-(2,4-Dichlorobenzyl) oximes 8a, 16a and 20a were significantly effective in delaying the onset of the PTZ-evoked seizures at the dose of 30mg/kg in kindled animals. The most effective compounds in delaying seizures were 7-chlorochromanone-O-(2,4-dichlorobenzyl) oximes 8a and 20a. SAR studies showed that introduction of a chlorine atom to the 7-position and/or a methyl group to the 2-position of the chroman ring resulted in an improvement of anti-seizure efficacy in O-(2,4-dichlorobenzyl) oxime series.