Maslen, Hannah L, Hughes, David, Hursthouse, Mike, De Clercq, Erik, Balzarini, Jan and Simons, Claire  ORCID: https://orcid.org/0000-0002-9487-1100
2004.
6-Azapyrimidine-2'-deoxy-4'-thionucleosides: potent antiviral agents in TK+ and TK- HSV and VZV viral strains.
Journal of Medicinal Chemistry
47
(22)
, pp. 5482-5491.
10.1021/jm049806q
|
Abstract
The synthesis of a series of novel 1-(2-deoxy-4-thio-?-d-erythro-pentofuranosyl)-(6-azapyrimidine) nucleosides is described. X-ray crystallographic data of the thymidine derivative allowed conformational analysis, which indicated a twist (3T2) sugar conformation. Hydrogen-bonded assemblies for the crystal structure were determined using PLATON software to allow further interpretation of the crystal packing and base interactions. The 6-azapyrimidine nucleosides described were evaluated against a range of viral strains. The thymidine analogue showed pronounced activity against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), varicella-zoster virus (VZV), and vaccinia virus. This compound lost only 5- to 10-fold of its antiviral activity against thymidine kinase (TK)-deficient HSV-1 and VZV strains. These observations suggest that the compounds may not entirely depend on viral TK-catalyzed phosphorylation for antiviral activity and/or use an alternative metabolic activation pathway, and/or display a unique mechanism of antiviral action by the unmetabolized nucleoside analogue.
| Item Type: | Article |
|---|---|
| Date Type: | Publication |
| Status: | Published |
| Schools: | Schools > Pharmacy |
| ISSN: | 00222623 |
| Last Modified: | 17 Oct 2022 08:45 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/947 |
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