149312-19-6Relevant academic research and scientific papers
1,5-anhydrohexitol nucleoside analogues
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, (2008/06/13)
1,5-Anhydrohexitol nucleoside analogues represented by the general formula I: STR1 wherein the hexitol has the D-configuration and the carbon atom on which the base moiety and the X substituent stand both have the (S)-configuration and further wherein: B is a heterocyclic ring selected from the group consisting of pyrimidine and purine bases; and X is hydrogen, azido, F, Cl, Br, I, amino, --NHR2, --N(R2)2, --OR2, --SR2, or CN; wherein R1 and R2 are the same or different and are selected from the group consisting of hydrogen, substituted or unsubstituted C1 -C20 alkyl, substituted or unsubstituted C1 -C20 alkenyl, aroyl, C1 -C20 alkanoyl, and phosphoryl. These nucleoside analogues are useful as antiviral agents against herpes simplex virus, vaccina virus, or varicella zoster virus. The definition of the X group should include --N(R2)2 instead of --N(N2)2.
Synthesis and antiherpes virus activity of 1,5-anhydrohexitol nucleosides
Verheggen,Van Aerschot,Toppet,Snoeck,Janssen,Balzarini,De Clercq,Herdewijn
, p. 2033 - 2040 (2007/10/02)
The synthesis of 1,5-anhydrohexitol nucleosides is described. These nucleoside analogues were obtained by alkylation of the heterocyclic bases with the tosylate 10 or by alkylation of the bases with the alcohol 12 under Mitsunobu conditions. The compounds were evaluated for antiviral and cytostatic activity. Highly selective activity against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) was noted for 1,5-anhydro-2,3-dideoxy-2- (5-iodouracil-1-yl)-D-arabino-hexitol 4b at a concentration of 0.07 μg/mL. This activity must be dependent on a specific phosphorylation by the virus- encoded thymidine kinase (TK), since compound 4b was inactive against TK- deficient mutants of HSV-1. The corresponding cytosine 4c and guanine 4e analogues showed activity against HSV-1, HSV-2, and other herpes viruses (i.e. cytomegalovirus, varicella-zoster virus) at concentrations well below the cytotoxicity threshold (2 and 20 μg/mL, respectively). At these concentrations, compounds 4c and 4e proved also inhibitory to the growth of human T-cells (i.e. MT-4, CEM, MOLT-4).
