Synthesis and in-vitro pharmacological evaluation of new 5-HT1A receptor ligands containing a benzotriazinone nucleus

Arch Pharm (Weinheim). 2008 Jan;341(1):20-7. doi: 10.1002/ardp.200700151.

Abstract

This paper reports the microwave-assisted synthesis and the binding assays on the 5-HT(1A), 5-HT(2A) and 5-HT(2C) receptors of new benzotriazinone derivatives, in order to identify selective ligands for the 5-HT(1A) subtype receptor. Conventional and microwave heating of the reactions were compared. Good yields and short reaction times are the main advantages of our synthetic route. More active compounds were selected and further evaluated for their binding affinities on D(1), D(2) dopaminergic and alpha(1), alpha(2) adrenergic receptors. The 3-(2-(4-(naphthalen-1-yl)piperazin-1-yl)ethyl)benzo[d][1,2,3]triazin-4(3H)-one 5 with K(i)= 0.000178 nM was the most active and selective derivative for the 5-HT(1A)receptor with respect to other serotonin receptors and the most selective derivative compared to dopaminergic and adrenergic receptors.

MeSH terms

  • Animals
  • Binding Sites
  • Cerebral Cortex / metabolism
  • Corpus Striatum / metabolism
  • In Vitro Techniques
  • Ligands
  • Male
  • Microwaves
  • Naphthalenes / chemical synthesis*
  • Naphthalenes / chemistry
  • Naphthalenes / pharmacology
  • Piperazines / chemical synthesis*
  • Piperazines / chemistry
  • Piperazines / pharmacology
  • Radioligand Assay
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Serotonin, 5-HT1A / metabolism*
  • Structure-Activity Relationship
  • Triazines / chemical synthesis*
  • Triazines / chemistry
  • Triazines / pharmacology

Substances

  • 3-(2-(4-(naphthalen-1-yl)piperazin-1-yl)ethyl)benzo(d)(1,2,3)triazin-4(3H)-one
  • Ligands
  • Naphthalenes
  • Piperazines
  • Triazines
  • Receptor, Serotonin, 5-HT1A