Purines nucleoside derivatives

Purine Nucleoside Derivatives. A number of purine nucleoside analogues are also found to be active against several DNA vimses (Fig. 3). The clinically active antiviral drug ara-A (9-P-D-arabinofuranosyladenine [5536-17-4] vidarabine, 23) is active against a number of DNA vimses in vivo and also inhibits certain RNA tumor vimses which repHcate through a DNA intermediate (43). Ara-A, was first synthesized in 1960 (44) and later... 

One of the most fruitful developments in purine chemistry within the last two decades was the discovery that acyclic purine nucleoside derivatives are very potent inhibitors of the proliferation of certain viruses. " In acyclic purine nucleosides, the ribose moiety is replaced by an acyclic chain corresponding to the upper or lower part of the /I-D-ribofuranose ring. The most important acyclic purine nucleosides are shown by the structures of acyclovir (Zovirax, ACV, acyclo G, 1), DHPG (2), DHPA (3), and PMEA (4). 

II. The Structure of Purine Nucleosides Derived from Nucleic Acids. 302... 

II. The Stbuctubb of Purine Nucleosides Derived FROM Nucleic Acids... 

Evidence for the /3-d configuration of the anomeric center (C-1) of the purine nucleosides derived from the nucleic acids was obtained by Fur-berg, using x-ray crystallographic analysis, and by Todd and coworkers, whose studies of the anhydronucleosides (7 and 8) derived from... 

Anomeric Purine Nucleoside Derivatives of 2-Amino-2-deoxy-D-glucose, M. L. Wolfrom, H. G. Garg, and D. Horton, Chem. Ind. (London), 930 (1964). 

Progress in synthesis, fluorescent, and biochemical properties of etheno-substituted purine nucleoside derivatives 06CJO1457. 

Another deviation from the normal displacement reaction of primary tosylates occurs in nucleoside derivatives (39, 81) where cyclonucleosides and anhydronucleosides are formed by participation of a nitrogen atom (as in purine nucleosides) and oxygen atom (as in pyrimidine nucleosides ), respectively. Iodonucleosides can result from these reactions only if these cyclic compounds are prone to attack by iodide ion. Several new examples of unexpected reactions during the solvolysis of sulfonate esters in sugar derivatives have been recorded in the past few years (2, 4,5,7,15,44,62,63,94). 

Adenosine deaminase deficiency is associated with an immunodeficiency disease in which both thymus-derived lymphocytes (T cells) and bone marrow-derived lymphocytes (B cells) are sparse and dysfunctional. Purine nucleoside phosphorylase deficiency is associated with a severe deficiency of T cells but apparently normal B cell function. Immune dysfunctions appear to result from accumulation of dGTP and dATP, which inhibit ribonucleotide reductase and thereby deplete cells of DNA precursors. 

Of the purine nucleosides, dATP may be derivatized at its N-6 position using a long linker arm terminating in a detectable group without losing the ability to be enzymatically incorporated into DNA probes. By contrast, if modification is done at the C-8 position of purine bases, DNA polymerase cannot by used to add the labeled monomer to an existing strand. C-8 derivatives, however, can be added at the 3 terminal using terminal transferase enzyme. 

Secrist, S. Y. Babu, C. E. Bugg, W. C. Guida, and S. E. Ealick, Structure-based design of inhibitors of purine nucleoside phosphorylase, 3,9-arylmethyl derivatives of a 9-deazaguanine substituted on the methylene group, J. Med. Chem. 36 3771 (1993). 

In 1975, Ranganathan used the OZT derived from D-arabinofuranose as a precursor to purine nucleosides.14,15 The D-xylofuran-fused OZT was reported later by Imbach et al.16,11 for the same purpose of synthesizing a- and /1-D-xylofuranosyl nucleosides. 

Unsaturated monosaccharides [e.g. (91)] react with the Ph3P-DAD combination in the presence of phthalimide, with inversion of configuration of C-4, to form the phthalimido-derivatives (92).82 Treatment of carbohydrates having a free anomeric OH group with 6-chloropurine, DAD, and methyldiphenylphosphine gives the purine nucleosides (93).83... 

Aciclovir, a synthetic purine nucleoside analogue derived from guanine, has in vitro inhibitory activity against members of the herpes virus family. 

The fluorine atom can be present in position 5 in uracil derivatives, or in position 1 in that of purine, as in fludarabine, which is used in the treatment of some leukemias (Figure 6.14 cf. Chapter 8). Nucleoside derivatives of fluorouracil (e.g., capecitabine) are prodrugs that allow the oral administration of 5-FU in cancer chemotherapy. The mechanism of action of these nucleosides is detailed in Chapters 7 and 8. Nucleosides having a trifluoromethylated base have been described for example, trifluridine is active on herpesvirus (Figure 6.14). 

Chemical Class Acyclic purine nucleoside analog acyclovir derivative Ciinicai Pharmacology ... 

Ultraviolet (UV) spectroscopy does not tend to be the method of choice for structure determination, but a list of UV absorptions was given in the review by Knowles <1996CHEC-II(7)489>. Fluorescence properties and triplet yields of [l,2,3]triazolo[4,5-r/ pyridazines in various solvents have been reported <2002JPH83>. These heterocyclic systems were found to be photochemically very stable. In a recent paper, Wierzchowski et al. studied the fluorescence emission properties of 8-azaxanthine ([l,2,3]triazolo[4,5-r/ pyrimidine-5,7-dione) and its A -alkyl derivatives at various pH s <2006JPH276>. For the 8-azaxanthines, an important characteristic of emission spectra in aqueous solutions was the unusually large Stokes shift. Since 8-azaxanthine is a substrate for purine nucleoside phosphorylase II from Escherichia coli, the reaction is now monitored fluorimetrically. The fluorescence properties of [l,2,3]triazolo[4,5-r/ -pyrimidine ribonucleosides were earlier described by Seela et al. <2005HCA751>. 

The reactions of 23 with 2, 3 -0-isopropylidene derivatives of purine nucleosides, or with free adenosine, give the corresponding N3,5 -anhydronucleosides in high yield a 5 -deoxy-5 -iodo deriv-... 

Montgomery JA, Niwas S, Rose JD, Secrist JA 3d., Babu YS, Bugg CE, Erion MD, Guida WC, Ealick SE. Structure-based design of inhibitors of purine nucleoside phosphorylase. 1. 9-(arylmethyl) derivatives of 9-deazaguinine. J Med Chem 1993 36 55-69. 

For compound 4 there is no recorded spectrum, but compound 5 is reported204 to absorb at 258 nm (e = 4300) in methanol solution. Jain and Anand have reported spectra for the four Af-methyl derivatives 111-114 in acid, neutral, and basic media149 of the two compounds 113 and 114 the spectrum of compound 5 most resembles the former, leading to a 1H-tautomer as the predominant structure. A more recent report205- of the spectrum of compound 111 differs considerably from that given by Jain and Anand. Because of the similarity of systems 4 and 5 to purine (nucleosides from both have been prepared), there has been much interest in the spectra of the amino derivatives and of the triazolopyridinones. For the [1,2,4]triazolo-[4,5-6]pyridines, spectra are reported for the 5-amino derivatives 115,187 116,194 117,153 and 118166 for the 3-amino derivatives 119 and 120181 and for... 

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