Novel nucleosides

The search for new antivkal agents is ongoing and extensive not all vimses have been included here, and new vimses pathogenic to humans will continue to be identified. Novel nucleosides as weU as nonnucleosidic compounds which possess greater potency and enzymic specificity for the future treatment of both acute and persistent human vkal infection will continue to be discovered. 

Kim, I., Song, X., Vig, B.S., Mittal, S., Shin, H.-C., Lorenzi, P.J. and Amidon, G.L., A novel nucleoside prodrug-activating enzyme substrate specificity of biphenyl hydrolase-like protein. Mol. Pharm., 2004,1, 117-127. 

Ethynylcytidine [l-(3-C-ethynyl-p-D-ribopentafuranosyl)-cytosine] (ETC) is a novel nucleoside that was foimd to be highly cytotoxic (53-55). By combination of ETC with NOAC, we synthesized the new lipophilic derivative NOAC-ETC [3 -C-ethynylcytidylyl-(5 —>5 )-N" -octadecyl-l-p-D-arabinofura-nosylcytosine]. The chemical structure of ETC-NOAC is shown in Fig. 1. 

A few papers on phosphonate chemistry have appeared.235-237 The synthesis of die novel nucleoside bicyclic trisanhydrides (256 A = adenosin-r -yl) has been reported.235 A kinetic sriidy of the alkaline hydrolysis of 4-substiriited phenyl ethyl benzyl phosphonates (257) supports an associative A-E mechanism for the hydrolysis.236 The direct preparation of the esters of /Miitrobenzylphosphonic acid from /r-nitrobenzyl halides has been reported.237... 

Walker et studied the oxidation of 2 -deoxy-5-ethyl-4 -thiouridine with sodium metaperiodate to afford a separable mixture of R and S sulfoxides 165 (5 1, 62%). The R isomer was converted, after protection, by reaction with LDA to the I anion, which was treated with a number of electrophiles to furnish novel nucleosides analogues, such as 166, which w as deprotectedto 167 withtriethylamine-trihydrogen fluoride. 

Griffin, L. C., Tidmarsh, G. E., Bock, L. C., Toole, J. J., Keung, L. L. K. (1993). In vivo anticoagulant properties of a novel nucleoside-based thrombin inhibitor and demonstration of regional anticoagulation in extracorporeal circuits. Blood 81, 3271-3276. 

Tobias SC, Borch RF (2001) Synthesis and biological studies of novel nucleoside phosphoramidate prodrugs. J Med Chem 44 4475-4480... 

Derivatives for nucleic acids have been reviewed [48]. The application of TMS and d9-labelled TMS derivatives is useful in the structure elucidation of newly discovered nucleosides [49]. Recent examples include the GC-MS (SIM) of trimethylsilylated nucleosides in the assessment of DNA damage [50] and the identification of a novel nucleoside, l,N -dimethyladenosine, in human cancer urine [51]. 

C. Strassler, N. E. Davis and E. T. Kool, Novel nucleoside analogues with fluorophores replacing the DNA base, Helv. Chim. Acta, 82, 2160-2171 (1999). 

Seki Jl, Shimada N, Takahashi K, T ita T, Takeuchi T, Hoshirso H. Inhibition of infKtivtty of HIV by a novel nucleoside, oxetanocin, and related compounds. Antimicrob Agents Chemolher 1989 33 773—775. 

Novel nucleoside analogues have been prepared by thermal intramolecular addition of the 5 -azido group of the uridine derivative (58) to the 5,6-doubIe bond of the pyrimidine ring. The main product was shown to be the macrocycle (59) together with some of the 6-amino-6,5 -cyclonucleoside. Heating... 

Veldkamp, A.I. Sparidans, R.W. Hoetelmans, R.M.W. Beijnen, J.H. Quantitative determination of abacavir (1592U89), a novel nucleoside reverse transcriptase inhibitor, in human plasma using isocratic reversed-phase high-performance liquid chromatography with ultraviolet detection, J.Chromatogr.B, 1999, 736, 123-128. 

Lipka, E., Glacon, V., Mackenzie, G., Ewing, D., Len, C., Postel, D., Vaccher, M. P., Bonte, J. P. and Vaccher, C. HPLC Separation and Determination of Enantiomeric Purity of Novel Nucleoside Analogs, on Cyclodextrin Chiral Stationary Phases, Using Reversed and Polar Organic Modes. Anal. Lett 37 385, 2004. 

M. Tanaka, A. Matsuda, T. Terao, and T. Sasaki, Antitumor activity of a novel nucleoside, 2 -C-cyano-... 

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