2-[4-[3-(4-aryl/heteroaryl-1-piperazinyl)propoxy]phenyl]-2H- benzotriazoles and their N-oxides as ligands for serotonin and dopamine receptors

Farmaco. 1999 Jun 30;54(6):402-10. doi: 10.1016/s0014-827x(99)00046-4.

Abstract

A small set of 2-{4-[3-(4-aryl/heteroaryl-piperazinyl)propoxy]phenyl}-2H-benzo tri azoles and corresponding N-oxides were prepared. The synthesized compounds were able to bind on some serotonin (5-HT1A, 5-HT2A) and dopamine (D2, D3) receptors, while displaying poor or no affinity for 5-HT1B, 5-HT2C, 5-HT3, and 5-HT4 subtypes. The strong contribution of the N-oxide function for the binding on 5-HT1A, D2 and D3 receptors is noteworthy. For 2-{4-[3-[4-(2-methoxyphenyl)-1-piperazinyl]propoxy]phenyl}-2H-benzotr iazole- 1-oxide (4b), the binding constants (Ki) were 11.9 (5-HT1A) and 10.5 nM (D3). In a general pharmacological screening, the 2-{4-[3-(4-phenyl-1-piperazinyl)propoxy]phenyl}-2H-benzotriazole (3a) exhibited only very weak activities, with the exception of protecting mice from cyanide-induced hypoxia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding, Competitive / drug effects
  • Dopamine Agents / chemical synthesis*
  • Dopamine Agents / pharmacology
  • Dopamine Agonists / metabolism
  • Ligands
  • Magnetic Resonance Spectroscopy
  • Mice
  • Neostriatum / drug effects
  • Neostriatum / metabolism
  • Olfactory Bulb / drug effects
  • Olfactory Bulb / metabolism
  • Radioligand Assay
  • Rats
  • Receptors, Dopamine / drug effects
  • Receptors, Serotonin / drug effects
  • Serotonin Agents / chemical synthesis*
  • Serotonin Agents / pharmacology
  • Spectrophotometry, Ultraviolet
  • Spiperone / metabolism
  • Structure-Activity Relationship
  • Tetrahydronaphthalenes / metabolism
  • Triazoles / chemical synthesis*
  • Triazoles / pharmacology

Substances

  • Dopamine Agents
  • Dopamine Agonists
  • Ligands
  • Receptors, Dopamine
  • Receptors, Serotonin
  • Serotonin Agents
  • Tetrahydronaphthalenes
  • Triazoles
  • Spiperone
  • 7-hydroxy-2-N,N-dipropylaminotetralin