Document Report Card

ID: ALA1142867

Journal: J Med Chem

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

Authors: Krecmerová M, Holý A, Pískala A, Masojídková M, Andrei G, Naesens L, Neyts J, Balzarini J, De Clercq E, Snoeck R.

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.

CiteXplore: 17298047

DOI: 10.1021/jm061281+