1. Academic Validation
  2. Antiviral activity of triazine analogues of 1-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine (cidofovir) and related compounds

Antiviral activity of triazine analogues of 1-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine (cidofovir) and related compounds

  • J Med Chem. 2007 Mar 8;50(5):1069-77. doi: 10.1021/jm061281+.
Marcela Krecmerová 1 Antonín Holý Alois Pískala Milena Masojídková Graciela Andrei Lieve Naesens Johan Neyts Jan Balzarini Erik De Clercq Robert Snoeck
Affiliations

Affiliation

  • 1 Gilead Sciences & IOCB Research Centre, Centre for New Antivirals and Antineoplastics (IOCB), Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic. marcela@uochb.cas.cz
Abstract

Treatment of 5-azacytosine sodium salt with diisopropyl [(2-chloroethoxy)methyl]phosphonate followed by removal of ester groups with BrSi(CH3)3 afforded 1-[2-(phosphonomethoxy)ethyl]-5-azacytosine (3). Reaction of 5-azacytosine with [(trityloxy)methyl]-(2S)-oxirane followed by etherification with diisopropyl (bromomethyl)phosphonate and removal of ester groups gave 1-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]-5-azacytosine (1). The synthesis of 6-azacytosine congener 2 was analogous using N4-benzoylated intermediates. Compound 1 was shown to exert strong activity against a broad spectrum of DNA viruses including adenoviruses, poxviruses, and herpesviruses (i.e., herpes simplex viruses, varicella zoster virus, and human cytomegalovirus). Decomposition of 1 in alkaline solutions resulted in products 17 and 18. While the N-formylguanidine derivative 17 proved active, the carbamyolguanidine derivative 18 was devoid of Antiviral activity.

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