Noncompetitive NMDA antagonists: a novel synthesis of 1-phenyltetrahydro-3-benzazepines

Arch Pharm (Weinheim). 1997 Jul;330(7):211-4. doi: 10.1002/ardp.19973300705.

Abstract

The key step in the synthesis of the pharmacologically interesting 1-phenyltetrahydro-3-benzazepine skeleton is the Michael addition of (2-lithiophenyl)acetaldehyde acetals, which are generated in situ upon treatment of the bromo acetals 5a,b with n-butyllithium, to beta-nitrostyrene (6). The reductive ring closure of the nitro acetals 7a,b succeeded with zinc dust and hydrochloric acid to give the 3-benzazepines 11a,b in good yields. The unsubstituted 3-benzazepine 11a showed a considerable affinity for the phencyclidine binding site of the NMDA receptor (Ki = 6.41 microM), whereas donor substituents in the aryl moiety (11b,c) reduce the affinity for the NMDA receptor.

MeSH terms

  • Benzazepines / chemical synthesis*
  • Benzazepines / pharmacology*
  • Binding, Competitive
  • N-Methylaspartate / antagonists & inhibitors*
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Structure-Activity Relationship

Substances

  • Benzazepines
  • Receptors, N-Methyl-D-Aspartate
  • N-Methylaspartate