NMDA-NR2B subtype selectivity of stereoisomeric 2-(1,2,3,4-tetrahydro-1-isoquinolyl)ethanol derivatives

Bioorg Med Chem Lett. 2005 May 2;15(9):2231-4. doi: 10.1016/j.bmcl.2005.03.025.

Abstract

Enantiopure 2-(1,2,3,4-tetrahydro-1-isoquinolyl)ethanol derivatives were tested for their affinity to the ifenprodil binding site of the NMDA receptor, their potency to inhibit [3H]MK801 binding and their NMDA-NR2B subtype selectivity. The (1S,1'S)-configurated series displayed the highest affinity to the ifenprodil binding site. A reasonable potency and NMDA-NR2B subtype selectivity was found for (1S,1'S)-4c (R1=Me, R2=OMe). A high affinity to HERG K+ channels, however, suggests that (1S,1'S)-4c may involve an increased risk of cardiovascular side effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Dizocilpine Maleate / pharmacokinetics
  • Ethanol / analogs & derivatives*
  • Ethanol / chemical synthesis
  • Ethanol / pharmacology*
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Isoquinolines / chemical synthesis*
  • Isoquinolines / pharmacology*
  • Kinetics
  • Models, Molecular
  • Molecular Structure
  • Potassium Channels / physiology
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
  • Stereoisomerism

Substances

  • 2-(1,2,3,4-tetrahydro-1-isoquinolyl)ethanol
  • Excitatory Amino Acid Antagonists
  • Isoquinolines
  • NR2B NMDA receptor
  • Potassium Channels
  • Receptors, N-Methyl-D-Aspartate
  • Ethanol
  • Dizocilpine Maleate