3a,4-二氢-3H-茚并[1,2-c]吡唑-2-甲酰胺/甲硫酰胺类似物的合成及抗惊厥活性。
Synthesis and anticonvulsant activity of 3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide/carbothioamide analogues.
机构信息
Department of Pharmaceutical Chemistry, New Drug Discovery Research, Alwar Pharmacy College, Alwar, India.
出版信息
J Enzyme Inhib Med Chem. 2013 Jun;28(3):644-50. doi: 10.3109/14756366.2012.663364. Epub 2012 Mar 7.
A series of fourteen 3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide/carbothioamide analogues were synthesized and evaluated for anticonvulsant activity according to the Antiepileptic Drug Development Programme (ADD) protocol. Some of the synthesized compounds showed significant activity in minimal clonic seizure model (6 Hz psychomotor seizure test). 3-(4-Fluorophenyl)-N-(4-bromophenyl)-6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide (4c) was found to be the most active compound of the series showing 75% (3/4, 0.25-2.0 h) and 50% (2/4, 4.0 h) protection against minimal clonic seizure at 100 mg/kg without any toxicity. 3-(Pyridin-4-yl)-N-(4-chlorophenyl)-6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide (4f) showed protection in maximal electroshock (MES) seizure and subcutaneous metrazol (scMET) seizure at 300 mg/kg.
合成了一系列 14 种 3a,4-二氢-3H-茚并[1,2-c]吡唑-2-甲酰胺/甲脒类似物，并根据抗癫痫药物开发计划（ADD）方案评估其抗惊厥活性。一些合成的化合物在最小阵挛性癫痫模型（6 Hz 运动性癫痫试验）中表现出显著的活性。3-(4-氟苯基)-N-(4-溴苯基)-6,7-二甲氧基-3a,4-二氢-3H-茚并[1,2-c]吡唑-2-甲酰胺（4c）是该系列中最活跃的化合物，在 100mg/kg 时对最小阵挛性癫痫的保护率分别为 75%（3/4，0.25-2.0 h）和 50%（2/4，4.0 h），无任何毒性。3-(吡啶-4-基)-N-(4-氯苯基)-6,7-二甲氧基-3a,4-二氢-3H-茚并[1,2-c]吡唑-2-甲酰胺（4f）在 300mg/kg 时对最大电休克（MES）癫痫发作和皮下美索比妥（scMET）癫痫发作具有保护作用。
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