Tritylamino aromatic heterocycles and related carbinols as blockers of ca 2+-activated potassium ion channels underlying neuronal hyperpolarization

Arch Pharm (Weinheim). 2002 Apr;335(4):159-66. doi: 10.1002/1521-4184(200204)335:4<159::AID-ARDP159>3.0.CO;2-K.

Abstract

A series of novel aromatic tritylamino heterocycles has been synthesized and the compounds have been tested in comparison with clotrimazole for their ability to inhibit the slow afterhyperpolarization current (sI (AHP)) in cultured rat hippocampal pyramidal neurones. Some analogues of the clotrimazole metabolite, 2-chlorophenyl-diphenyl methanol, having different chlorination substitution in the triphenyl group have also been examined. Two compounds in particular, 3-[(2-chlorophenyl)-diphenylmethylamino] pyridine (3a, UCL 1880) and 2-tritylaminothiazole (6, UCL 2027), are of special interest; they are effective blockers of the sI (AHP) (IC (50) = 1.1-1.2 microM) and are much more selective than clotrimazole since they have less effect on the high voltage-activated Ca2+ current.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Animals
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Cells, Cultured
  • Clotrimazole / analogs & derivatives
  • Clotrimazole / pharmacology
  • Female
  • Heterocyclic Compounds / chemical synthesis*
  • In Vitro Techniques
  • Male
  • Models, Molecular
  • Neurons / drug effects
  • Neurons / metabolism*
  • Neurons / physiology
  • Potassium Channels, Calcium-Activated / antagonists & inhibitors*
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Structure-Activity Relationship

Substances

  • Heterocyclic Compounds
  • Potassium Channels, Calcium-Activated
  • Clotrimazole