PHOSPHORAMIDATE DERIVATIVES OF 2′,5′-DIDEOXYADENOSINE AS POTENTIAL INHIBITORS OF THE EDHF PHENOMENON

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.

Keywords:

• EDHF Phenomenon
• Phosphoramidate
• Protide