Phosphoramidate derivatives of 2',5'-dideoxyadenosine as potential inhibitors of the EDHF phenomenon.
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.
Gavazza
F
F
Welsh School of Pharmacy, Redwood Building, Cardiff University, Cardiff CFIO 3XF, UK. sphfg2@cf.ac.uk
Daverio
F
F
Chaytor
A T
AT
Griffith
T M
TM
McGuigan
C
C
D000067956:Adenylyl Cyclase Inhibitors; D000577:Amides / Q000737:chemistry*; D000818:Animals; D001158:Arteries / Q000187:drug effects; D002626:Chemistry, Pharmaceutical / Q000379:methods; D016048:Dideoxyadenosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D009711:Nucleotides / Q000737:chemistry; D010756:Phosphoric Acids / Q000737:chemistry*; D011817:Rabbits; D014680:Veins / Q000187:drug effects
D000067956:Adenylyl Cyclase Inhibitors; D000577:Amides; D009711:Nucleotides; D010756:Phosphoric Acids; D016048:Dideoxyadenosine; C021008:2',5'-dideoxyadenosine; C011067:phosphoramidic acid