1573094-58-2Relevant articles and documents
N-aryl-2,6-dimethylbenzamides, a new generation of tocainide analogues as blockers of skeletal muscle voltage-gated sodium channels
Muraglia, Marilena,De Bellis, Michela,Catalano, Alessia,Carocci, Alessia,Franchini, Carlo,Carrieri, Antonio,Fortugno, Cecilia,Bertucci, Carlo,Desaphy, Jean-Fran?ois,De Luca, Annamaria,Conte Camerino, Diana,Corbo, Filomena
, p. 2589 - 2600 (2014/04/17)
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.
