Acyclic nucleoside phosphonates with 5-azacytosine base moiety substituted in C-6 position

Bioorganic & Medicinal Chemistry
Marcela KrecmerováA Holý

Abstract

Two methods for preparation of 6-substituted derivatives of anti DNA-viral agent 1-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]-5-azacytosine (HPMP-5-azaC) were developed: (1) ammonia mediated ring-opening reaction of diisopropyl esters of HPMP-5-azaC (4) to carbamoylguanidine derivatives followed by ring-closure reaction with orthoesters and (2) condensation reaction of 6-substituted 5-azacytosines with diisopropyl (1S)-[2-hydroxy-1-tosyloxymethyl)ethoxy]methylphosphonate (15). Deprotection of diisopropyl esters to free phosphonic acids was performed with bromotrimethylsilane in acetonitrile followed by hydrolysis. In contrast to parent compound HPMP-5-azaC, a substantial decrease of antiviral activity in case of 6-substituted analogues occurred. Surprisingly, N-3 isomer of 6-methyl-HPMP-5-azaC in the form of isopropyl ester revealed activity against RNA viruses (Sindbis virus).

References

Aug 2, 2002·The Laryngoscope·Steven BielamowiczWilliam R Wilson
Apr 22, 2008·International Journal of Cancer. Journal International Du Cancer·Carlo Stresemann, Frank Lyko

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Citations

Jun 2, 2012·Future Medicinal Chemistry·Marcela Krečmerová, Miroslav Otmar
Mar 13, 2014·Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy·Magdy SheblMona A A Kishk
Dec 9, 2020·Antimicrobial Agents and Chemotherapy·Nichodemus O OnwubikoHeinz Peter Nasheuer
Mar 25, 2021·Archiv der Pharmazie·Saumya SinghUdaya P Singh

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