Synthesis and anticonvulsant evaluation of N-substituted isoquinoline AMPA receptor antagonists

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• 作者：Rosaria Gitto ; Laura De Luca ; Benedetta Pagano ; Rita Citraro ; Giovanbattista De Sarro ; Lara Costa ; Lucia Ciranna ; Alba Chimirri
• 关键词：Isoquinolines ; Microwave-assisted synthesis ; Anticonvulsant agents ; AMPA-antagonists ; Molecular modelling
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2008
• 出版时间：1 March 2008
• 年：2008
• 卷：16
• 期：5
• 页码：2379-2384
• 全文大小：411 K

文摘

In our previous studies a ligand-based approach led to the identification of noncompetitive AMPA receptor antagonists containing isoquinoline scaffold. In an attempt to perform a systematic SAR study, we synthesized new N-substituted-isoquinolines bearing the most salient features described by our 3D pharmacophore model. All compounds were screened against audiogenic seizures and some derivatives showed anticonvulsant properties. Compound 24, the most active of the series, was also tested in vitro using the patch–clamp technique and proved to antagonize AMPA-mediated effects.