2-Aminothiazole based P2Y(1) antagonists as novel antiplatelet agents

Bioorg Med Chem Lett. 2013 Jul 15;23(14):4206-9. doi: 10.1016/j.bmcl.2013.05.025. Epub 2013 May 17.

Abstract

ADP receptors, P2Y1 and P2Y12 have been recognized as potential targets for antithrombotic drugs. A series of P2Y1 antagonists that contain 2-aminothiazoles as urea surrogates were discovered. Extensive SAR of the thiazole ring is described. The most potent compound 7j showed good P2Y1 binding (Ki=12nM), moderate antagonism of platelet aggregation (PA IC50=5.2μM) and acceptable PK in rats.

MeSH terms

  • Aminopyridines / chemistry*
  • Aminopyridines / metabolism
  • Aminopyridines / pharmacokinetics
  • Animals
  • Blood Platelets / metabolism
  • Half-Life
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / chemistry*
  • Platelet Aggregation Inhibitors / metabolism
  • Platelet Aggregation Inhibitors / pharmacokinetics
  • Protein Binding
  • Purinergic P2Y Receptor Antagonists / chemistry*
  • Purinergic P2Y Receptor Antagonists / metabolism
  • Purinergic P2Y Receptor Antagonists / pharmacokinetics
  • Rats
  • Receptors, Purinergic P2Y1 / chemistry*
  • Receptors, Purinergic P2Y1 / metabolism
  • Structure-Activity Relationship
  • Thiazoles / chemistry*
  • Thiazoles / metabolism
  • Thiazoles / pharmacokinetics

Substances

  • Aminopyridines
  • Platelet Aggregation Inhibitors
  • Purinergic P2Y Receptor Antagonists
  • Receptors, Purinergic P2Y1
  • Thiazoles
  • 2-aminothiazole