Synthesis, radiolabeling, and preliminary biological evaluation of [3H]-1-[(S)-N,O-bis-(isoquinolinesulfonyl)-N-methyl-tyrosyl]-4-(o-tolyl)-piperazine, a potent antagonist radioligand for the P2X7 receptor

Bioorg Med Chem Lett. 2004 Nov 15;14(22):5709-12. doi: 10.1016/j.bmcl.2004.07.095.

Abstract

The design, synthesis, and preliminary biological evaluation of the first potent radioligand antagonist for the P2X(7) receptor, named [(3)H]-1-[(S)-N,O-bis-(isoquinolinesulfonyl)-N-methyl-tyrosyl]-4-(o-tolyl)-piperazine (compound 13), are reported. This compound bound to human P2X(7) receptors expressed in HEK transfected cells with K(D) and B(max) value of 3.46+/-0.1 nM and 727+/-73 fmol/mg of protein, respectively. The high affinity and facile labeling makes it a promising radioligand for a further characterization of P2X(7) receptor subtype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arylsulfonates / chemical synthesis*
  • Arylsulfonates / pharmacology*
  • Binding Sites
  • Drug Design
  • Evaluation Studies as Topic
  • Humans
  • Isotope Labeling / methods*
  • Ligands
  • Molecular Structure
  • Purinergic P2 Receptor Antagonists*
  • Receptors, Purinergic P2X7
  • Structure-Activity Relationship
  • Tritium / chemistry*
  • Tyrosine / analogs & derivatives*
  • Tyrosine / chemical synthesis*
  • Tyrosine / pharmacology*

Substances

  • 1-(N,O-bis(isoquinolinesulfonyl)-N-methyltyrosyl)-4-(4-fluorophenyl)piperazine
  • Arylsulfonates
  • Ligands
  • P2RX7 protein, human
  • Purinergic P2 Receptor Antagonists
  • Receptors, Purinergic P2X7
  • Tritium
  • Tyrosine