3,4-Dihydro-2H-benzoxazinones as dual-acting 5-HT1A receptor antagonists and serotonin reuptake inhibitors

Bioorg Med Chem Lett. 2007 Feb 15;17(4):1033-6. doi: 10.1016/j.bmcl.2006.11.031. Epub 2006 Nov 15.

Abstract

Investigation of halogen substitution in lead compound 1 has led to the identification of analogues which combine high affinity for 5-HT(1A) receptors and potent serotonin reuptake inhibitory activity. Several compounds show an improved selectivity over 5-HT(1B) and 5-HT(1D) receptors and a superior pharmacokinetic profile in the rat.

MeSH terms

  • Animals
  • Benzoxazines / chemical synthesis*
  • Benzoxazines / pharmacology*
  • Binding, Competitive / drug effects
  • CHO Cells
  • Callithrix
  • Cell Line
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Cricetinae
  • Cricetulus
  • Guinea Pigs
  • Humans
  • Indicators and Reagents
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Models, Molecular
  • Piperazines / pharmacology
  • Pyridines / pharmacology
  • Radioligand Assay
  • Rats
  • Receptor, Serotonin, 5-HT1A / drug effects*
  • Receptor, Serotonin, 5-HT1B / drug effects
  • Receptor, Serotonin, 5-HT1D / drug effects
  • Selective Serotonin Reuptake Inhibitors / chemical synthesis*
  • Selective Serotonin Reuptake Inhibitors / pharmacology*
  • Serotonin Antagonists / chemical synthesis*
  • Serotonin Antagonists / pharmacology*
  • Synaptosomes / drug effects

Substances

  • Benzoxazines
  • Indicators and Reagents
  • Piperazines
  • Pyridines
  • Receptor, Serotonin, 5-HT1B
  • Receptor, Serotonin, 5-HT1D
  • Serotonin Antagonists
  • Serotonin Uptake Inhibitors
  • Receptor, Serotonin, 5-HT1A
  • N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide