We have recently reported that 2′,3'dideoxy analogues of our exquisitely potent anti-VZV furanopyrimidine deoxynucleosides are shifted to selective anti-HCMV agents. We now find that the fully deoxygenated 2′,3′,5′-trideoxy analogue is fully antivirally active. This is taken as proof that these agents act by a novel non-nucleoside mechanism of action.
BalzariniJ & McGuiganC (2002) Bicyclic pyrimidine nucleoside analogues (BCNAs) as highly selective and potent inhibitors of varicella-zoster virus replication. Journal of Antimicrobial Chemotherapy50: 5–9.
2.
LittlerEStuartAD & CheeMS (1992) Human cytomegalovirus UL-97 open reading frame encodes a protein that phosphorylates the antiviral nucleoside analogue ganciclovir. Nature358: 160–162.
3.
McGuiganCYarnoldCJJonesGVelázquezSBaruckiHBrancaleAAndreiGSnoeckRDe ClercqE & BalzariniJ (1999) Potent and selective inhibition of varicella-zoster virus (VZV) by nucleoside analogues with an unusual bicyclic base. Journal of Medicinal Chemistry42: 4479–4484.
4.
McGuiganCBaruckiHBrancaleABlewettSCarangioAJonesGPathiranaRSrinivasanSVelázquezSYarnoldCJAlvarezRAndreiGSnoeckRDe ClercqE & BalzariniJ (2000) Fluorescent bicyclic furo pyrimidine deoxynucleoside analogues as potent and selective inhibitors of VZV and potential future drugs for the treatment of chickenpox and shingles. Drugs of the Future25: 1151–1161.
5.
McGuiganCBaruckiHBlewettSCarangioAErichsenJTAndreiGSnoeckRDe ClercqE & BalzariniJ (2000a) Highly potent and selective inhibition of varicella-zoster virus by bicyclic furo pyrimidine nucleosides bearing an aryl side chain. Journal of Medicinal Chemistry43: 4993–4997.
6.
McGuiganCBrancaleABaruckiHSrinivasanSJonesGPathiranaRCarangioABlewettSLuoniGBidetOJukesAJarvisCAndreiGSnoeckRDe ClercqE & BalzariniJ (2001) Furano pyrimidines as novel potent and selective anti-VZV agents. Antiviral Chemistry & Chemotherapy12: 77–89.
7.
McGuiganCPathiranaRNSnoeckRAndreiGDe ClercqE & BalzariniJ (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 Chemistry47: 1847–1851.
8.
SekineM & NakanishiT (1990) Facile synthesis of 3′-O-methylthymidine and 3′-deoxythymidine and related deoxygenated thymidine derivatives: A new method for selective deoxygenation of secondary hydroxy groups. Journal of Organic Chemistry55: 924.
9.
SienaertRNaesensLBrancaleADe ClercqEMcGuiganC & BalzariniJ (2001) Specific recognition of the bicyclic pyrimidine nucleoside analogues, a new class of highly potent and selective inhibitors of varicella-zoster virus (VZV), by the VZV-encoded thymidine kinase. Molecular Pharmacology61: 249–254.
10.
SnoeckRAndreiGBodaghiBLagneauxLDaelemansDDe ClercqENeytsJScholsDNaesensLMichelsonSBronDOttoM.J.BousseauANemecekC & RoyC (2002) 2-Chloro-3-pyridin-3-yl-5,6,7,8-tetrahydroindolizine-1-carboxamide (CMV423), a new lead compound for the treatment of human cytomegalovirus infections. Antiviral Research44: 413–424.
