8-[2-(4-Aryl-1-piperazinyl)ethyl]-2H-1,4-benzoxazin-3(4H)-ones: dual-acting 5-HT1 receptor antagonists and serotonin reuptake inhibitors--part II

Bioorg Med Chem Lett. 2009 Apr 15;19(8):2338-42. doi: 10.1016/j.bmcl.2009.02.056. Epub 2009 Feb 20.

Abstract

8-[2-(4-Aryl-1-piperazinyl)ethyl]-2H-1,4-benzoxazin-3(4H)-ones have been identified as highly potent 5-HT(1A/B/D) receptor antagonists with and without additional SerT activity and a high degree of selectivity over hERG potassium channels. Modulation of the different target activities gave compounds with a range of profiles suitable for further in vivo characterization.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Benzoxazines / chemistry*
  • Benzoxazines / metabolism
  • Benzoxazines / pharmacology
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • ERG1 Potassium Channel
  • Ether-A-Go-Go Potassium Channels / antagonists & inhibitors
  • Ether-A-Go-Go Potassium Channels / metabolism
  • Humans
  • Piperazines / chemistry*
  • Piperazines / metabolism
  • Piperazines / pharmacology
  • Rats
  • Receptors, Serotonin, 5-HT1 / metabolism
  • Selective Serotonin Reuptake Inhibitors / chemistry*
  • Selective Serotonin Reuptake Inhibitors / metabolism
  • Selective Serotonin Reuptake Inhibitors / pharmacology
  • Serotonin 5-HT1 Receptor Antagonists*
  • Serotonin Antagonists / chemistry*
  • Serotonin Antagonists / metabolism
  • Serotonin Antagonists / pharmacology

Substances

  • Benzoxazines
  • ERG1 Potassium Channel
  • Ether-A-Go-Go Potassium Channels
  • KCNH2 protein, human
  • Piperazines
  • Receptors, Serotonin, 5-HT1
  • Serotonin 5-HT1 Receptor Antagonists
  • Serotonin Antagonists
  • Serotonin Uptake Inhibitors