Enantiomeric propanolamines as selective N-methyl-D-aspartate 2B receptor antagonists.

Journal Article (Journal Article)

Enantiomeric propanolamines have been identified as a new class of NR2B-selective NMDA receptor antagonists. The most effective agents are biaryl structures, synthesized in six steps with overall yields ranging from 11-64%. The compounds are potent and selective inhibitors of NR2B-containing recombinant NMDA receptors with IC 50 values between 30-100 nM. Potency is strongly controlled by substitution on both rings and the centrally located amine nitrogen. SAR analysis suggests that well-balanced polarity and chain-length factors provide the greatest inhibitory potency. Structural comparisons based on 3D shape analysis and electrostatic complementarity support this conclusion. The antagonists are neuroprotective in both in vitro and in vivo models of ischemic cell death. In addition, some compounds exhibit anticonvulsant properties. Unlike earlier generation NMDA receptor antagonists and some NR2B-selective antagonists, the present series of propanolamines does not cause increased locomotion in rodents. Thus, the NR2B-selective antagonists exhibit a range of therapeutically interesting properties.

Full Text

Duke Authors

Cited Authors

  • Tahirovic, YA; Geballe, M; Gruszecka-Kowalik, E; Myers, SJ; Lyuboslavsky, P; Le, P; French, A; Irier, H; Choi, W-B; Easterling, K; Yuan, H; Wilson, LJ; Kotloski, R; McNamara, JO; Dingledine, R; Liotta, DC; Traynelis, SF; Snyder, JP

Published Date

  • September 25, 2008

Published In

Volume / Issue

  • 51 / 18

Start / End Page

  • 5506 - 5521

PubMed ID

  • 18800760

Pubmed Central ID

  • PMC3142473

Electronic International Standard Serial Number (EISSN)

  • 1520-4804

Digital Object Identifier (DOI)

  • 10.1021/jm8002153


  • eng

Conference Location

  • United States