Sodium channel binding and anticonvulsant activities of hydantoins containing conformationally constrained 5‐phenyl substituents

Academic Article


  • As a preliminary investigation of the importance of the aromatic ring orientation in interactions of 5‐phenylhydantoins with the anticonvulsant site on the neuronal voltage‐sensitive sodium channel, two isomeric hydantoins containing conformationally constrained phenyl rings and their monocyclic analogues were synthesized. One, a spiro‐hydantoin (2) derived from α‐tetralone, contains the plane of the phenyl ring in an orientation approximately perpendicular to that for the hydan‐toin ring. The other, a tricyclic hydantoin (4) derived from tetrahydroiso‐quinoline, contains the plane of the phenyl ring in an orientation roughly coplanar with that for the hydantoin ring. These compounds were evaluated in sodium channel binding and whole animal (mice) anticonvulsant assays. In both assays, 4 was significantly more potent than 2, suggesting that the anticonvulsant receptor site on the voltage‐sensitive sodium channel may require a specific aromatic ring orientation. Copyright © 1990 Wiley‐Liss, Inc., A Wiley Company
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    Digital Object Identifier (doi)

    Author List

  • Brouillette WJ; Brown GB; Delorey TM; Liang G
  • Start Page

  • 871
  • End Page

  • 874
  • Volume

  • 79
  • Issue

  • 10