Synthesis and binding affinity of new 1,4-disubstituted triazoles as potential dopamine D(3) receptor ligands

Bioorg Med Chem Lett. 2013 Oct 15;23(20):5586-91. doi: 10.1016/j.bmcl.2013.08.047. Epub 2013 Aug 16.

Abstract

A series of new 1,4-disubstituted triazoles was prepared from appropriate arylacetylenes and aminoalkylazides using click chemistry methodology. These compounds were evaluated as potential ligands on several subtypes of dopamine receptors in in vitro competition assays, showing high affinity for dopamine D3 receptors, lower affinity for D2 and D4, and no affinity for the D1 receptors. Compound 18 displayed the highest affinity at the D3 receptor with a Ki value of 2.7 nM, selectivity over D2 (70-fold) and D4 (200-fold), and behaviour as a competitive antagonist in the low nanomolar range.

Keywords: 1,2,3-Triazoles; Binding assays; Click chemistry; Dopamine receptors; Microwaves; Synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Click Chemistry
  • Dopamine D2 Receptor Antagonists
  • Humans
  • Kinetics
  • Ligands*
  • Piperazines / chemical synthesis*
  • Piperazines / chemistry
  • Piperazines / metabolism
  • Protein Binding
  • Receptors, Dopamine D1 / agonists
  • Receptors, Dopamine D1 / antagonists & inhibitors
  • Receptors, Dopamine D1 / metabolism
  • Receptors, Dopamine D2 / agonists
  • Receptors, Dopamine D2 / metabolism
  • Receptors, Dopamine D3 / agonists
  • Receptors, Dopamine D3 / antagonists & inhibitors
  • Receptors, Dopamine D3 / chemistry
  • Receptors, Dopamine D3 / metabolism*
  • Triazoles / chemical synthesis
  • Triazoles / chemistry*
  • Triazoles / metabolism

Substances

  • Dopamine D2 Receptor Antagonists
  • Ligands
  • Piperazines
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Triazoles