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Subject: Pyrimidines ×

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Now showing 1 - 4 of 4
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    Pyrimidine acyclo-C-nucleosides by ring transformations of 2-formyl-L-arabinal
    (Basel : MDPI, 2005) Bari, A.; Feist, H.; Michalik, M.; Peseke, K.
    The protected 2-formyl-L-arabinal 2 reacted with thiourea and cyanamide in the presence of sodium hydride to afford via ring transformations the 5-[1R,2S-1,2-bis(benzyloxy)-3-hydroxypropyl]-1,2-dihydropyrimidines 3 and 4, respectively. Similarly, treatment of 2 with 3-amino-2H-1,2,4-triazole yielded 6-[1R,25-1,2-bis(benzyloxy)-3-hydroxypropyl][1,2,4]-triazolo[1,5-a]pyrimidine(5) .
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    Anti-Prion Drug mPPIg5 Inhibits PrPC Conversion to PrPSc
    (San Francisco, CA : Public Library of Science, 2013) McCarthy, J.M.; Franke, M.; Resenberger, U.K.; Waldron, S.; Simpson, J.C.; Tatzelt, J.; Appelhans, D.; Rogers, M.S.
    Prion diseases, also known as transmissible spongiform encephalopathies, are a group of fatal neurodegenerative diseases that include scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle and Creutzfeldt-Jakob disease (CJD) in humans. The 'protein only hypothesis' advocates that PrPSc, an abnormal isoform of the cellular protein PrPC, is the main and possibly sole component of prion infectious agents. Currently, no effective therapy exists for these diseases at the symptomatic phase for either humans or animals, though a number of compounds have demonstrated the ability to eliminate PrPSc in cell culture models. Of particular interest are synthetic polymers known as dendrimers which possess the unique ability to eliminate PrPSc in both an intracellular and in vitro setting. The efficacy and mode of action of the novel anti-prion dendrimer mPPIg5 was investigated through the creation of a number of innovative bio-assays based upon the scrapie cell assay. These assays were used to demonstrate that mPPIg5 is a highly effective anti-prion drug which acts, at least in part, through the inhibition of PrPC to PrPSc conversion. Understanding how a drug works is a vital component in maximising its performance. By establishing the efficacy and method of action of mPPIg5, this study will help determine which drugs are most likely to enhance this effect and also aid the design of dendrimers with anti-prion capabilities for the future.
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    Dimethylaminomethylene-α-D-xylo-hept-5-ulofuranurononitrile as building block in the synthesis of 'reversed' C-nucleoside analogues
    (Berlin : de Gruyter, 2006) Hashmi, I.A.; Feist, H.; Michalik, M.; Reinke, H.; Peseke, K.
    3-O-Benzyl-6-deoxy-1,2-O-isopropylidene-6-(dimethylaminomethylene) -α-D-xylo-hept-5-ulofuranurononitrile (1) was reacted with amidinium salts, S-methylisothiouronium sulfate, and guanidinium chloride, respectively, in the presence of bases to furnish the 4-(3-O-benzyl-1,2-O-isopropylidene- α-D-xylo-tetrofuranos-4-yl)pyrimidine-5-carbonitriles 2 and the 4-(1,2-O-isopropylidene-α-D-glycero-tetr-3-enofuranos-4-yl) pyrimidine-5-carbonitriles 3, respectively. Treatment of 1 with ethyl 5-aminopyrazole-4-carboxylates yielded the ethyl 7-(3-O-benzyl-1,2-O- isopropylidene-α-D-xylo-tetrofuranos-4-yl)-6-cyanopyrazolo[1,5-a] pyrimidine-3-carboxylates 4 and the ethyl 7-amino-6-(3-O-benzyl-1,2-O- isopropylidene-α-D-xylo-pentofuranuronoyl)pyrazolo[1,5-a] pyrimidine-3-carboxylates 5, respectively. Reaction of 1 with 2-benzimidazolylacetonitrile in the presence of sodium methanolate afforded 1-amino-2-(3-O-benzyl-1,2-O-isopropylidene-α-D-xylo-pentofuranuronoyl) benzo[4,5]imidazo[1,2-a]pyridine-4-carbonitrile (6) and 1-amino-2-(3-deoxy-1,2- O-isopropylidene-α-D-glycero-pent-S-enofuranuronoyl)benzo[4,5]imidazo[1, 2-a]pyridine-4-carbonitrile (7). © 2006 Verlag der Zeitschrift für Naturforschung.
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    Nucleoside analogues from push-pull functionalized branched-chain pyranosides
    (Berlin : de Gruyter, 2006) Kordian, M.; Feist, H.; Kantlehner, W.; Michalik, M.; Peseke, K.
    The reaction of methyl 4,6-O-benzylidene-2-deoxy-α-D-erythro- hexopyranosid-3-ulose (1) with ethynylmagnesium bromide in tetrahydrofuran and subsequent trimethylsilylation yielded the methyl 4,6-O-benzylidene-2-deoxy-3-C- ethynyl-3-O-trimethylsilyl-α-D-ribo-hexopyranoside (3). Push-pull functionalization of 3 with N,N,N′,N′,N″,N″- hexamethylguanidinium chloride under basic conditions and following deprotection afforded the spiro{2,5-dihydro-3-dimethylamino-furan-2,8'-4',4'a,6',7',8',8'a- hexahydro-6'-methoxy-2'-phenyl-pyrano[3,2-d][1,3]dioxine}-5- ylidenemalononitrile (9). Furthermore, compound 1 reacted with N,N-dimethylformamide dimethylacetal to furnish methyl (E)-4,6-O-benzylidene-2- deoxy-2-dimethylaminomethylene-α-D-erythro-hexopyranosid-3-ulose (10). Treatment of 10 with methylhydrazine and amidines yielded (4S,5aR,8R,9aS)-2,5a, 6,9a-tetrahydro-4-methoxy-2-methyl-8-phenyl-4H-[1,3]dioxino[4',5':5,6]pyrano[4, 3-c]pyrazole (11a) and (2R,4aR,6S,10bS)-4,4a,6,10b-tetrahydro-6-methoxy-2- phenyl[1,3]dioxino[4',5':5,6]pyrano[4,3-d]pyrimidines 12, respectively. © 2006 Verlag der Zeitschrift für Naturforschung.