Benzyloxybenzylammonium chlorides: Simple amine salts that display anticonvulsant activity

Hyosung Lee, Alexander S. Gold, Xiao Fang Yang, Rajesh Khanna, Harold Kohn

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Several antiepileptic drugs exert their activities by inhibiting Na + currents. Recent studies demonstrated that compounds containing a biaryl-linked motif (Ar-X-Ar′) modulate Na+ currents. We, and others, have reported that compounds with an embedded benzyloxyphenyl unit (ArOCH2Ar′, OCH2 = X) exhibit potent anticonvulsant activities. Here, we show that benzyloxybenzylammonium chlorides ( +H3NCH2C6H4OCH 2Ar′ Cl-) displayed notable activities in animal seizure models. Electrophysiological studies of 4-(2′- trifluoromethoxybenzyloxy)benzylammonium chloride (9) using embryonic cortical neurons demonstrated that 9 promoted both fast and slow inactivation of Na + channels. These findings suggest that the potent anticonvulsant activities of the earlier compounds were due, in part, to the benzyloxyphenyl motif and provide support for the use of the biaryl-linked pharmacophore in future drug design efforts.

Original languageEnglish (US)
Pages (from-to)7655-7662
Number of pages8
JournalBioorganic and Medicinal Chemistry
Volume21
Issue number24
DOIs
StatePublished - Dec 15 2013
Externally publishedYes

Keywords

  • Antiepileptic agents
  • Benzyloxybenzylammonium chlorides
  • Biaryl-linked motif
  • Na current inhibition

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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