European Journal of Medicinal Chemistry 2008-11-01

Constrained analogues of tocainide as potent skeletal muscle sodium channel blockers towards the development of antimyotonic agents.

Alessia Catalano, Alessia Carocci, Filomena Corbo, Carlo Franchini, Marilena Muraglia, Antonio Scilimati, Michela De Bellis, Annamaria De Luca, Diana Conte Camerino, Maria Stefania Sinicropi, Vincenzo Tortorella

Index: Eur. J. Med. Chem. 43(11) , 2535-40, (2008)

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Abstract

1-Benzyl-N-(2,6-dimethylphenyl)piperidine-3-carboxamide and 4-benzyl-N-(2,6-dimethylphenyl)piperazine-2-carboxamide, two conformationally restricted analogues of tocainide, were designed and synthesized as voltage-gated skeletal muscle sodium channel blockers. They showed, with respect to tocainide, a marked increase in both potency and use-dependent block.