N-aryl-2,6-dimethylbenzamides, a new generation of tocainide analogues as blockers of skeletal muscle voltage-gated sodium channels.
作者： Marilena Muraglia , Michela De Bellis , Alessia Catalano , Alessia Carocci , Carlo Franchini
DOI: 10.1021/JM401864B
关键词: Skeletal muscle 、 Stereochemistry 、 Pharmacophore 、 Aryl 、 Tocainide 、 Potency 、 Sodium channel blocker 、 Sodium channel 、 Chemistry
摘要: On the basis of a 3D-QSAR study, new generation tocainide analogues were designed and synthesized as voltage-gated skeletal muscle sodium channel blockers. Data obtained by screening compounds means Hille-Campbell Vaseline gap voltage-clamp recordings showed that elongation alkyl chain introduction lipophilic sterically hindered groups on amino function enhance both potency use-dependent block. The results provide additional indications about structural requirement pharmacophores for further increasing state-dependent block allowed us to identify analogue (6f) with favorable pharmacodynamic profile be proposed valid candidate studies aimed at evaluating its usefulness in treatment myotonias.
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