Ester prodrugs of cyclic 1-(S)- [3-hydroxy-2-(phosphonomethoxy)propyl]-5-azacytosine: synthesis and antiviral activity.

Ester prodrugs of cyclic 1-(S)- [3-hydroxy-2-(phosphonomethoxy)propyl]-5-azacytosine: synthesis and antiviral activity. Research Abstract Details 

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Ester prodrugs of cyclic 1-(S)- [3-hydroxy-2-(phosphonomethoxy)propyl]-5-azacytosine: synthesis and antiviral activity. Abstract Text:

Marcela , ,Radek Pohl,Milena ,Graciela Andrei,Lieve Naesens,Johan Neyts,Jan Balzarini,Erik De Clercq,Robert Snoeck,Marcela , ,Radek Pohl,Milena ,Graciela Andrei,Lieve Naesens,Johan Neyts,Jan Balzarini,Erik De Clercq,Robert Snoeck,

Reaction of 1-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]-5-azacytosine (1) with dicyclohexylcarbodiimide and N,N,-dicyclohexyl-4-morpholinocarboxamidine in dimethylformamide at elevated temperature afforded the corresponding cyclic phosphonate 2, that is, 1-{[(5S)-2-hydroxy-2-oxido-1,4,2-dioxaphosphinan-5-yl]methyl}-5-azacytosine. Compound 2 exerts strong in vitro activity against DNA viruses, comparable with activity of parent compound 1. Transformation of 2 to its tetrabutylammonium salt followed by reaction with alkyl or acyloxyalkyl halogenides enabled us to prepare a series of structurally diverse ester prodrugs: alkyl (octadecyl), alkenyl (erucyl), alkoxyalkyl (hexadecyloxyethyl), and acyloxyalkyl (pivaloyloxymethyl) (3-6). The introduction of an alkyl, alkoxyalkyl, or acyloxyalkyl ester group to the molecule resulted in an increase of antiviral activity; the most active compound was found to be the hexadecyloxyethyl ester 5. The relative configuration of the diastereoisomer trans-6 was determined using H,H-NOESY NMR.

Ester prodrugs of cyclic 1-(S)- [3-hydroxy-2-(phosphonomethoxy)propyl]-5-azacytosine: synthesis and antiviral activity. Publishing Authors By Initials

M ,A ,R Pohl,M ,G Andrei,L Naesens,J Neyts,J Balzarini,E De Clercq,R Snoeck,M ,A ,R Pohl,M ,G Andrei,L Naesens,J Neyts,J Balzarini,E De Clercq,R Snoeck,

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Ester prodrugs of cyclic 1-(S)- [3-hydroxy-2-(phosphonomethoxy)propyl]-5-azacytosine: synthesis and antiviral activity. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of medicinal chemistry

VOLUME: 50

Page Numbers: 5765-72

Journal Abbreviation: J. Med. Chem.

ISSN: 0022-2623

DAY: 19

MONTH: 10

YEAR: 2007

Ester prodrugs of cyclic 1-(S)- [3-hydroxy-2-(phosphonomethoxy)propyl]-5-azacytosine: synthesis and antiviral activity. Information

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LANGUAGE: eng

NlmUniqueID: 9716531

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Grant and Affiliation Information for Ester prodrugs of cyclic 1-(S)- [3-hydroxy-2-(phosphonomethoxy)propyl]-5-azacytosine: synthesis and antiviral activity.

AFFILIATION: Gilead Sciences and IOCB Research Centre, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic. marcela@uochb.cas.cz

Country: United States

AGENCY: United States NIAID

GRANT: 1UC1 AI062540-01

ACRONYM: AI

MEDLINETA: J Med Chem

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