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

Eur J Med Chem. 2008 Nov;43(11):2535-40. doi: 10.1016/j.ejmech.2008.01.023. Epub 2008 Jan 31.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Molecular Structure
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / metabolism
  • Myotonia*
  • Sodium Channel Blockers / chemical synthesis*
  • Sodium Channel Blockers / chemistry
  • Sodium Channel Blockers / pharmacology*
  • Structure-Activity Relationship
  • Tocainide / analogs & derivatives
  • Tocainide / chemical synthesis*
  • Tocainide / chemistry
  • Tocainide / pharmacology*

Substances

  • Sodium Channel Blockers
  • Tocainide