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Discovery of a new family of inhibitors of human cytomegalovirus (HCMV) based upon lipophilic alkyl furano pyrimidine dideoxy nucleosides: Action via a novel non-nucleosidic mechanism

McGuigan, Christopher, Andrei, E, Pathirana, RN and Snoeck, R 2004. Discovery of a new family of inhibitors of human cytomegalovirus (HCMV) based upon lipophilic alkyl furano pyrimidine dideoxy nucleosides: Action via a novel non-nucleosidic mechanism. Journal of Medicinal Chemistry 47 (7) , pp. 1847-1851. 10.1021/jm030857h

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Abstract

Following our discovery of the potent anti-varicella zoster virus action of lipophilic alkyl furano pyrimidine 2‘-deoxynucleosides, we now report that 2‘,3‘-dideoxy sugar analogues are devoid of anti-VZV activity but are potent and selective inhibitors of human cytomegalovirus (HCMV). The present compounds are active in vitro at ca. 1 μM with cytotoxicity only above 200 μM. Importantly, we have discovered that the new agents do not act as nucleoside analogues, despite their nucleosidic structure, and time of addition studies revealed that the compounds may inhibit HCMV at an event in the replication cycle of the virus that precedes DNA synthesis. They represent new leads in the discovery of improved therapies for HCMV, particularly in view of their novel mechanism of action.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
Systems Immunity Research Institute (SIURI)
Publisher: ACS Publications
ISSN: 0022-2623
Last Modified: 18 Oct 2017 08:41
URI: http://orca.cf.ac.uk/id/eprint/937

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