Synthesis and dopamine receptor binding of 3-phenylazepino[5,4,3-c,d]indole derivatives

Arch Pharm (Weinheim). 1995 Apr;328(4):329-32. doi: 10.1002/ardp.19953280407.

Abstract

The 3-phenylazepino[5,4,3-c,d]indole derivatives 5 and 9-11, representing heterocyclic analogs of the selective dopamine D-1 receptor ligands of the 3-phenylbenzazepine class, were synthesized starting from the indole-4-carboxylate 7. Receptor binding studies employing bovine striatal membranes demonstrated that the test compounds 5, 10, and 11 are able to displace the D-1 selective radioligand [3H]-SCH 23390 as well as the D-2 antagonist [3H]-spiperone. Compound 5b turned out to be the most potent and selective ligand (ki = 1.8 microM for D-1 and ki = 8.9 microM for D-2). It is assumed that the moderate selectivity of 5b is due to the conformational inequality of the 7-membered rings when compared to the benzazepines. This results in a spatial arrangement of the phenyl substituent which is not able to interact with a 'subtype selectivity-inducing site'.

MeSH terms

  • Animals
  • Azepines / chemical synthesis*
  • Azepines / pharmacology
  • Cattle
  • Dopamine Agents / chemical synthesis*
  • Dopamine Agents / pharmacology
  • Dopamine D2 Receptor Antagonists
  • In Vitro Techniques
  • Indoles / chemical synthesis*
  • Indoles / pharmacology
  • Radioligand Assay
  • Receptors, Dopamine D1 / antagonists & inhibitors

Substances

  • Azepines
  • Dopamine Agents
  • Dopamine D2 Receptor Antagonists
  • Indoles
  • Receptors, Dopamine D1