Effects of 5'-phosphate derivatives of 2-hexynyl adenosine and 2-phenylethynyl adenosine on responses of human platelets mediated by P2Y receptors

J Med Chem. 2005 Apr 21;48(8):2763-6. doi: 10.1021/jm0493562.

Abstract

Newly synthesized mono-, di-, and triphosphate of 2-alkynyl adenosines showed very different behavior in human platelet P2Y receptor models, according to the different alkynyl chains. In fact, 2-hexynyladenosine di- (5) and triphosphate (7) induced platelet shape change and aggregation and inhibited PGE(1)-induced increase in platelet cyclic AMP. On the contrary, the corresponding 2-phenylethynyladenosine di- (6) and triphosphate (8) did not induce platelet shape change or aggregation, but inhibited platelet aggregation induced by ADP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / chemical synthesis*
  • Adenosine / chemistry
  • Adenosine / pharmacology
  • Alkynes / chemical synthesis*
  • Alkynes / chemistry
  • Alkynes / pharmacology
  • Blood Platelets / cytology
  • Blood Platelets / drug effects*
  • Blood Platelets / physiology
  • Cell Shape / drug effects
  • Cyclic AMP / antagonists & inhibitors
  • Cyclic AMP / biosynthesis
  • Humans
  • In Vitro Techniques
  • Membrane Proteins / agonists
  • Membrane Proteins / drug effects*
  • Membrane Proteins / physiology
  • Organophosphates / chemical synthesis*
  • Organophosphates / chemistry
  • Organophosphates / pharmacology
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / chemical synthesis*
  • Platelet Aggregation Inhibitors / chemistry
  • Platelet Aggregation Inhibitors / pharmacology
  • Purinergic P2 Receptor Agonists
  • Purinergic P2 Receptor Antagonists
  • Receptors, Purinergic P2 / drug effects*
  • Receptors, Purinergic P2 / physiology
  • Receptors, Purinergic P2Y1
  • Receptors, Purinergic P2Y12
  • Structure-Activity Relationship

Substances

  • Alkynes
  • Membrane Proteins
  • Organophosphates
  • P2RY1 protein, human
  • P2RY12 protein, human
  • Platelet Aggregation Inhibitors
  • Purinergic P2 Receptor Agonists
  • Purinergic P2 Receptor Antagonists
  • Receptors, Purinergic P2
  • Receptors, Purinergic P2Y1
  • Receptors, Purinergic P2Y12
  • 2-hexynyladenosine
  • Cyclic AMP
  • Adenosine