Symmetrical diamidate prodrugs of nucleotide analogues for drug delivery

Current Protocols in Nucleic Acid Chemistry
Fabrizio PertusatiMichaela Serpi

Abstract

The use of pronucleotides to circumvent the well-known drawbacks of nucleotide analogs has played a significant role in the area of antiviral and anticancer drug delivery. Several motifs have been designed to mask the negative charges on the phosphorus moiety of either nucleoside monophosphates or nucleoside phosphonates, in order to increase their hydrophobicity and allow entry of the compound into the cell. Among them the bis-amidate analogs, having two identical amino acids as masking groups through a P-N bond, represent a more recent approach for the delivery of nucleotide analogs, endowed with antiviral or anticancer activity. Different synthetic strategies are commonly used for preparing phosphorodiamidates of nucleosides. In this protocol, we would like to focus on the description of the synthetic methodology that in our hand gave the best results using 2'-3'-didehydro-2'-3'-dideoxythymidine (d4T, Stavudine) as model nucleoside. A second strategy for preparing diamidates of nucleoside phosphonates will be reported using {[2-(6-amino-9 H-purin-9-yl)ethoxy]methyl}phosphonic acid (PMEA, adefovir) as model substrate.

References

Apr 16, 1993·Journal of Medicinal Chemistry·C McGuiganE De Clercq
Nov 4, 2000·Medicinal Research Reviews·C R WagnerE J McIntee
Mar 5, 2003·Bioorganic & Medicinal Chemistry·Carsten Schultz
Jun 25, 2003·Antimicrobial Agents and Chemotherapy·Kathy A KeithEarl R Kern
Aug 19, 2007·Journal of Pharmaceutical Sciences·Fujun LiTom Alfredson
Feb 2, 2008·Journal of Medicinal Chemistry·Scott J Hecker, Mark D Erion
May 3, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Hans ReiserDaniel B Tumas
Apr 23, 2009·Expert Opinion on Drug Delivery·Larryn W Peterson, Charles E McKenna
Aug 4, 2009·Journal of Medicinal Chemistry·Marco DerudasChristopher McGuigan
Nov 2, 2011·Journal of Medicinal Chemistry·Christopher McGuiganStanley Chamberlain
Dec 21, 2011·Antiviral Chemistry & Chemotherapy·Fabrizio PertusatiChristopher McGuigan
Jun 19, 2013·Current Protocols in Nucleic Acid Chemistry·Michaela SerpiMagdalena Slusarczyk
Nov 2, 2013·European Journal of Medicinal Chemistry·Christopher McGuiganJan Balzarini
Apr 2, 2014·European Journal of Medicinal Chemistry·Fabrizio PertusatiChristopher McGuigan
Apr 3, 2014·Bioorganic & Medicinal Chemistry·Christopher McGuiganSanjib Bhakta
May 9, 2014·The Journal of Organic Chemistry·Kiran S TotiSerge Van Calenbergh

❮ Previous
Next ❯

Citations

Aug 14, 2018·Current Protocols in Nucleic Acid Chemistry·Elisa PileggiFabrizio Pertusati

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Related Papers

Environmental Science & Technology
Current Protocols in Nucleic Acid Chemistry
Michaela SerpiMagdalena Slusarczyk
Environmental Science & Technology
© 2022 Meta ULC. All rights reserved