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ID: ALA4118253

Journal: Bioorg Med Chem

Title: Expedient synthesis and biological evaluation of alkenyl acyclic nucleoside phosphonate prodrugs.

Authors: Pileggi E, Serpi M, Andrei G, Schols D, Snoeck R, Pertusati F.

Abstract: The importance of phosphonoamidate prodrugs (ProTides) of acyclic nucleoside phosphonate (ANPs) is highlighted by the approval of Tenofovir Alafenamide Fumarate for the treatment of HIV and HBV infections. In the present paper we are reporting an expedient, one-pot, two-steps synthesis of allyl phosphonoamidates and diamidates that offers a time saving strategy when compared to literature methods. The use of these substrates in the cross metathesis reactions with alkenyl functionalised thymine and uracil nucleobases is reported. ANPs prodrugs synthesized via this methodology were evaluated for their antiviral activities against DNA and RNA viruses. It is anticipated that the use of 5,6,7,8-tetrahydro-1-napthyl as aryloxy moiety is capable to confer antiviral activity among a series of otherwise inactive uracil ProTides.

CiteXplore: 29880251

DOI: 10.1016/j.bmc.2018.05.034