Effects of log P and phenyl ring conformation on the binding of 5- phenylhydantoins to the voltage-dependent sodium channel

Academic Article

Abstract

  • Binding to the neuronal voltage-dependent sodium channel (NVSC) was evaluated for 12 5-phenylhydanteins which systematically varied either log P and/or 5-phenyl ring orientation. The linear correlation of log P with in vitro sodium channel binding activity (log IC50) for hydantoins 1-12 and diphenylhydantoin (DPH) (r2 = 0.638) suggested that simple partitioning into the lipid phase is important but not sufficient to account for the effects of hydantoins on the NVSC. Comparisons among different hydantoins with the same log P but different low-energy phenyl ring orientations revealed that, in addition to log P, the correct 5-phenyl orientation is important for efficient binding.
  • Published In

    Digital Object Identifier (doi)

    Author List

  • Brown ML; Brown GB; Brouillette WJ
  • Start Page

  • 602
  • End Page

  • 607
  • Volume

  • 40
  • Issue

  • 4