Expedient synthesis and biological evaluation of alkenyl acyclic nucleoside phosphonate prodrugs

Pileggi, Elisa, Serpi, Michaela ORCID: https://orcid.org/0000-0002-6162-7910, Andrei, Graciela, Schols, Dominique, Snoeck, Robert and Pertusati, Fabrizio ORCID: https://orcid.org/0000-0003-4532-9101 2018. Expedient synthesis and biological evaluation of alkenyl acyclic nucleoside phosphonate prodrugs. Bioorganic and Medicinal Chemistry 26 (12) , pp. 3596-3609. 10.1016/j.bmc.2018.05.034

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Pharmacy
Publisher:	Elsevier
ISSN:	0968-0896
Date of First Compliant Deposit:	11 June 2018
Date of Acceptance:	22 May 2018
Last Modified:	20 Nov 2023 13:14
URI:	https://orca.cardiff.ac.uk/id/eprint/112153

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