Synthesis and in vitro stability of nucleoside 5'-phosphonate derivatives.
Nucleoside derivatives are largely synthesized and tested to investigate their influence on platelet aggregation. It's well known that P2Y receptors play an important role in the regulation of platelet function and, as consequence, in controlling atherothrombotic events. The research of compounds that antagonize P2Y(1) and, in particular, P2Y(12) receptors is of great interest in the aim to obtain platelet aggregation inhibitors that are effective in the prevention and treatment of arterial thrombosis. In this study we present the synthesis and in vitro metabolic stability in human blood and rat liver homogenate of a new class of nucleoside derivatives, in particular 5'-phosphonate adenosine, inosine, guanosine and thioadenosine analogues also modified at the ribose moiety. On the basis of the results obtained we can hypothesize compounds 4 and 18 to have in vivo a relatively high stability.
Department of Pharmaceutical Sciences, University of Ferrara, via Fossato di Mortara 17-19, 44121 Ferrara, Italy. vrs@unife.it
Silvia
S
Vertuani
Anna
A
Baldisserotto
Katia
K
Varani
Pier Andrea
PA
Borea
Bonache
B
De Marcos Maria Cruz
Luca
L
Ferraro
Stefano
S
Manfredini
Alessandro
A
Dalpiaz
D000818:Animals; D060326:Chemistry Techniques, Synthetic; D004355:Drug Stability; D006801:Humans; D008099:Liver / Q000378:metabolism; D008297:Male; D009705:Nucleosides / Q000097:blood / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D063065:Organophosphonates / Q000737:chemistry*; D010975:Platelet Aggregation Inhibitors / Q000097:blood / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D009705:Nucleosides; D063065:Organophosphonates; D010975:Platelet Aggregation Inhibitors