Synthesis of 3a,4-dihydro-3H-[1]benzopyrano[4,3-c]isoxazoles, displaying combined 5-HT uptake inhibiting and alpha(2)-adrenoceptor antagonistic activities: a novel series of potential antidepressants

Bioorg Med Chem Lett. 2003 Aug 18;13(16):2719-25. doi: 10.1016/s0960-894x(03)00525-0.

Abstract

The synthesis of a series of novel 3-piperazinylmethyl-3a,4-dihydro-3H-[1]benzopyrano[4,3-c]isoxazoles as novel dual 5-HT reuptake inhibitors and alpha(2)-adrenoceptor antagonists is described. Their affinity at the three different human alpha(2)-adrenoceptor subtypes and the 5-HT transporter site is reported. The in vivo activity of the compounds was measured in two different assays: (1). inhibition of pCA-induced excitation, which evaluates the ability to block the central 5-HT transporter, and (2). inhibition of xylazine-induced loss of righting, which evaluates the ability to block central alpha(2)-adrenoceptors.

Publication types

  • Comparative Study

MeSH terms

  • Adrenergic alpha-Antagonists / chemical synthesis*
  • Adrenergic alpha-Antagonists / pharmacology*
  • Animals
  • Antidepressive Agents / chemical synthesis*
  • Antidepressive Agents / pharmacology*
  • Carrier Proteins / metabolism
  • Isoxazoles / chemical synthesis*
  • Isoxazoles / pharmacology
  • Membrane Glycoproteins / metabolism
  • Membrane Transport Proteins*
  • Molecular Structure
  • Nerve Tissue Proteins*
  • Rats
  • Selective Serotonin Reuptake Inhibitors / chemical synthesis*
  • Selective Serotonin Reuptake Inhibitors / pharmacology
  • Serotonin Plasma Membrane Transport Proteins
  • Stereoisomerism
  • Structure-Activity Relationship
  • Xylazine / antagonists & inhibitors

Substances

  • Adrenergic alpha-Antagonists
  • Antidepressive Agents
  • Carrier Proteins
  • Isoxazoles
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin Uptake Inhibitors
  • Slc6a4 protein, rat
  • Xylazine