A novel series of N-(hexahydro-1,4-diazepin-6-yl) and N-(hexahydroazepin- 3-yl)benzamides with high affinity for 5-HT3 and dopamine D2 receptors

Bioorg Med Chem Lett. 1998 Mar 17;8(6):619-24. doi: 10.1016/s0960-894x(98)00078-x.

Abstract

A novel series of benzamides with a hexahydro-1,4-diazepine or hexahydroazepine ring in the amine moiety were prepared, and their binding affinities for 5-HT3 and dopamine D2 receptors were evaluated. The R isomer of the 1-ethyl-4-methylhexahydro-1,4-diazepinylbenzamide (R)-22 had potent affinity for both receptors. The R-enantiomer of the corresponding 1-ethylhexahydroazepinylbenzamide 28 showed potent affinity for dopamine D2 receptors with reduced affinity for 5-HT3 receptors, while the S isomer was found to be a potent and selective 5-HT3 receptor antagonist.

MeSH terms

  • Animals
  • Benzamides / metabolism*
  • Binding Sites
  • Cerebral Cortex / metabolism
  • Corpus Striatum / metabolism
  • Domperidone / metabolism
  • Dopamine Antagonists / metabolism
  • Imidazoles / metabolism
  • Indoles / metabolism
  • Ligands
  • Metoclopramide / metabolism
  • Models, Chemical
  • Ondansetron / metabolism
  • Rats
  • Receptors, Dopamine D2 / metabolism*
  • Receptors, Serotonin / metabolism*
  • Receptors, Serotonin, 5-HT3
  • Serotonin Antagonists / metabolism
  • Spiperone / metabolism
  • Stereoisomerism

Substances

  • Benzamides
  • Dopamine Antagonists
  • Imidazoles
  • Indoles
  • Ligands
  • Receptors, Dopamine D2
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT3
  • Serotonin Antagonists
  • GR 65630
  • Ondansetron
  • Spiperone
  • Domperidone
  • Metoclopramide