Phosphoramidate derivatives of 2',5'-dideoxyadenosine as potential inhibitors of the EDHF phenomenon

Nucleosides Nucleotides Nucleic Acids. 2005;24(5-7):553-5. doi: 10.1081/ncn-200061809.

Abstract

P-site inhibitors of adenyl cyclase, such as the dideoxynucleosides 2',3'-ddA and 2',5-ddA, have been shown to attenuate EDHF phenomenon in rabbit arteries and veins. In order to present the dideoxynucleosides as pre-activated nucleotides and bypass the kinase, as well as to prevent their metabolism to dideoxyinosine by adenosine deaminase, the aryloxyphosphoramidate approach has been successfully applied, initially on the 2',3'-ddA. In the present work a new series of 2',5'-ddA phosphoramidates has been synthesized, representing the first example of phosphoramidate protide not at the 5'-position.

MeSH terms

  • Adenylyl Cyclase Inhibitors
  • Amides / chemistry*
  • Animals
  • Arteries / drug effects
  • Chemistry, Pharmaceutical / methods
  • Dideoxyadenosine / analogs & derivatives*
  • Dideoxyadenosine / chemistry
  • Dideoxyadenosine / pharmacology
  • Drug Design
  • Inhibitory Concentration 50
  • Models, Chemical
  • Nucleotides / chemistry
  • Phosphoric Acids / chemistry*
  • Rabbits
  • Veins / drug effects

Substances

  • Adenylyl Cyclase Inhibitors
  • Amides
  • Nucleotides
  • Phosphoric Acids
  • Dideoxyadenosine
  • 2',5'-dideoxyadenosine
  • phosphoramidic acid