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

F Gavazza, F Daverio, A T Chaytor, T M Griffith, C McGuigan

Index: Nucleosides Nucleotides Nucleic Acids 24(5-7) , 553-5, (2005)

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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.