Phosphoramidate derivatives of 2',5'-dideoxyadenosine as potential inhibitors of the EDHF phenomenon
F Gavazza1, F Daverio, A T Chaytor
1Welsh School of Pharmacy, Redwood Building, Cardiff University, Cardiff CFIO 3XF, UK. sphfg2@cf.ac.uk
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.
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