Synthesis and evaluation of arylpiperazines derivatives of 3,5-dioxo-(2H,4H)-1,2,4-triazine as 5-HT1AR ligands

Bioorg Med Chem Lett. 2014 Oct 1;24(19):4759-4762. doi: 10.1016/j.bmcl.2014.07.048. Epub 2014 Aug 14.

Abstract

5-HT1AR agonist or partial agonists are established drug candidates for psychiatric and neurological disorders. We have reported the synthesis and evaluation of a series of high affinity 5-HT1AR partial agonist PET imaging agents with greater selectivity over α-1AR. The characteristic of these molecules are 3,5-dioxo-(2H,4H)-1,2,4-triazine skeleton tethered to an arylpiperazine unit through an alkyl side chain. The most potent 5-HT1AR agonistic properties were found to be associated with the molecules bearing C-4 alkyl group as the linker. Therefore development of 3,5-dioxo-(2H,4H)-1,2,4-triazine bearing arylpiperazine derivatives may provide high affinity selective 5-HT1AR ligands. Herein we describe the synthesis and evaluation of the binding properties of a series of arylpiperazine analogues of 3,5-dioxo-(2H,4H)-1,2,4-triazine.

Keywords: 5-HT; 5-HT(1A)R; Agonist; Arylpiperazine; α-1AR.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Dose-Response Relationship, Drug
  • Humans
  • Ligands
  • Molecular Structure
  • Piperazines / chemical synthesis
  • Piperazines / chemistry*
  • Piperazines / pharmacology*
  • Receptor, Serotonin, 5-HT1A / metabolism*
  • Serotonin 5-HT1 Receptor Agonists / chemical synthesis
  • Serotonin 5-HT1 Receptor Agonists / chemistry
  • Serotonin 5-HT1 Receptor Agonists / pharmacology*
  • Structure-Activity Relationship
  • Triazines / chemical synthesis
  • Triazines / chemistry
  • Triazines / pharmacology*

Substances

  • Ligands
  • Piperazines
  • Serotonin 5-HT1 Receptor Agonists
  • Triazines
  • Receptor, Serotonin, 5-HT1A