Gitto Rosaria, De Luca Laura, Pagano Benedetta, Citraro Rita, De Sarro Giovanbattista, Costa Lara, Ciranna Lucia, Chimirri Alba
Dipartimento Farmaco-Chimico, Università di Messina, Viale Annunziata, 98168 Messina, Italy.
Bioorg Med Chem. 2008 Mar 1;16(5):2379-84. doi: 10.1016/j.bmc.2007.11.071. Epub 2007 Nov 29.
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.
在我们之前的研究中，基于配体的方法导致鉴定出含有异喹啉骨架的非竞争性AMPA受体拮抗剂。为了进行系统的构效关系（SAR）研究，我们合成了带有我们的3D药效团模型所描述的最显著特征的新型N-取代异喹啉。所有化合物都针对听源性癫痫进行了筛选，一些衍生物表现出抗惊厥特性。该系列中活性最高的化合物24也使用膜片钳技术进行了体外测试，并证明可拮抗AMPA介导的效应。
