A number of pyrimidine nucleosides, which may show two hydrogen bonding modes, have been prepared and tested for antiviral activity against a series of viruses. Whilst none of the compounds described showed significant activity against human immunodeficiency virus (HIV), the bicyclic 2′-deoxynucleoside, [2], derived from the base 6H,8H-3,4-dihydropyrimido[4,5-c][1,2]oxazin-7-one, was shown to inhibit herpes simplex virus type 1 (HSV-1) at similar concentrations as BVDU1 and ACV. Compounds 13, 6-(2-deoxyribofuranosyl)-6H,8H-2-methyl-3,4-dihydropyrimido[4,5-c][1,2]oxazin-7-one, and 14, N4-hydroxy-5-(2-chloroethyl)-2′-deoxyuridine, were as active as ACV against varicella-zoster virus (VZV).
BernaertsR.DesgrangesC., and De ClercqE. (1989) (E)-5-(2-Bromovinyl)uridine requires phosphorylation by the herpes simplex virus (type-1)-induced thymidine kinase to express its antiviral activity. Biochem Pharmacol38: 1955–1961.
2.
BischofbergerN. (1987) Synthesis of 4-C substituted pyrimidinenucleosides. Tetrahedron Letts28: 2821–2824.
3.
CzerneckiS.Le DiguarherT. and ValeryJ.M. (1993) Synthesis and anti-HIV-1 activity of base modified analogues of 3′-azido-2′,3′-dideoxythymidine (AZT)Nucleosides & Nucleotides12: 369–380.
4.
De ClercqE.DesgrangesC.HerdewijnP.SimI.S.JonesA.S.McCleanM.J. and WalkerR.T. (1986) Synthesis and antiviral activity of (E)-5-(2-bromovinyl)uracil and (E)-5-(2-bromovinyl)uridine. J Med Chem29: 213–217.
5.
GrienglH.BodenteichM.HaydenW.WanekE.StreicherW.StutzP.BachmayerH.GhazzouliI. and RosenwirthB. (1985) 5-Haloalkyl-2′-deoxyuridines: a novel type of potent antiviral nucleoside analogue. J Med Chem28: 1679–1684.
6.
HerdewijnP.BalzariniJ.BabaM.PauwelsR.JanssenG. and De ClercqE. (1988) Synthesis and anti-HIV activity of different sugar modified pyrimidine and purine nucleosides. J Med Chem31: 2040–2048.
7.
Kong Thoo LinP. and BrownD.M. (1989) Synthesis and duplex stability of oligonucleotides containing cytosinethymine analogues. Nucleic Acids Res17: 10373–10383.
8.
LiJ.KumarS.V.P.StuartA.L.TourignyG.DelbaereL.T.J. and GuptaS.V. (1994) 3′-Azido-2′,3′-dideoxy-5-hydroxymethyluridine. Acta Cryst Section C50: 1626–1629.
9.
LinT-S.GuoJ-Y.SchinaziR.F.ChuC.K.XiangJ-N. and PrusoffW.H. (1988). Synthesis and antiviral activity of various 3′-azido analogues of pyrimidine deoxyribonucleosides against human immunodeficiency virus (HIV-1, HTLV-III/LAV). J Med Chem31: 336–340.
10.
LoakesD. and BrownD.M. (1994) Synthesis of bicyclic N4-oxycytidine derivatives. Nucleosides & Nucleotides13: 679–688.
11.
LoakesD.BrownD.M.MahmoodN.BalziriniJ. and De ClercqE. (1995) Antiviral activity of N4-aminocytidine derivatives related to AZT. Antiviral Chem Chemother6: 9–16.
12.
MorozovY.U.SavinF.A.ChekhovV.O.BudowskyE.I. and YakovlevD.Y. (1982) Photochemistry of N6-methoxyadenosine and of N4-hydroxycytidine and its methyl derivatives I: spectroscopic and quantum chemical investigation of ionic and tautomeric forms: Syn-Anti isomerization. J Photochem20: 229–252.
13.
NasrM.LitterstC. and McGowanJ. (1990) Computer-assisted structure activity correlation's of dideoxynucleoside analogues as potential anti-HIV drugs, Antiviral Res14: 125–148.
14.
TourignyG.StuartA.L.EkieiI.AdumaP.J. and GuptaS.V. (1989) Conformation and antiherpes activity of 3′-and 5′-azido and amino analogues of 5-methoxymethyl-2′-deoxyuridine. Nucleosides & Nucleotides8: 1189–1200.
15.
Van MeerveltL. (1991) Structure of 3′,5′-di-O-acetyl-N4-methoxy-2′-deoxycytidine. Acta Cryst Section C47: 2635–2637.
16.
WebbT.R. and MatteucciM.D. (1986) Hybridization triggered cross-linking of deoxyoligonucleotides, Nucleic Acids Res14: 7661–7674.
