Document Report Card

ID: ALA3232895

Journal: J Med Chem

Title: N-aryl-2,6-dimethylbenzamides, a new generation of tocainide analogues as blockers of skeletal muscle voltage-gated sodium channels.

Authors: Muraglia M, De Bellis M, Catalano A, Carocci A, Franchini C, Carrieri A, Fortugno C, Bertucci C, Desaphy JF, De Luca A, Conte Camerino D, Corbo F.

Abstract: On the basis of a 3D-QSAR study, a new generation of tocainide analogues were designed and synthesized as voltage-gated skeletal muscle sodium channel blockers. Data obtained by screening new compounds by means of Hille-Campbell Vaseline gap voltage-clamp recordings showed that the elongation of the alkyl chain and the introduction of lipophilic and sterically hindered groups on the amino function enhance both potency and use-dependent block. The results provide additional indications about the structural requirement of pharmacophores for further increasing potency and state-dependent block and allowed us to identify a new tocainide analogue (6f) with a favorable pharmacodynamic profile to be proposed as a valid candidate for studies aimed at evaluating its usefulness in the treatment of myotonias.

CiteXplore: 24568674

DOI: 10.1021/jm401864b