Novel nucleotide triphosphates as potent P2Y2 agonists with enhanced stability over UTP

Bioorg Med Chem Lett. 2007 Jan 15;17(2):558-61. doi: 10.1016/j.bmcl.2006.10.038. Epub 2006 Oct 19.

Abstract

The synthesis of a series of novel C-linked nucleotide triphosphates is reported. These exhibit excellent agonist potency and selectivity for the P2Y2 receptor with a number of examples having EC50 values below 10 nM. Representative compounds from the N-linked and C-linked series showed enhanced metabolic stability compared with that of the natural ligand UTP.

MeSH terms

  • Cell Line, Tumor
  • Chromatography, Liquid
  • Humans
  • Indicators and Reagents
  • Ligands
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Nucleotides / chemical synthesis*
  • Nucleotides / chemistry
  • Nucleotides / pharmacology*
  • Purinergic P2 Receptor Agonists*
  • Receptors, Purinergic P2Y2
  • Recombinant Proteins
  • Spectrophotometry, Ultraviolet
  • Uridine Triphosphate / chemistry*
  • Uridine Triphosphate / pharmacology

Substances

  • Indicators and Reagents
  • Ligands
  • Nucleotides
  • P2RY2 protein, human
  • Purinergic P2 Receptor Agonists
  • Receptors, Purinergic P2Y2
  • Recombinant Proteins
  • Uridine Triphosphate