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• W1968703453 abstract "The synthesis, antiviral and pharmacokinetic properties of zanamivir (ZMV) dimers 8 and 13 are described. The compounds are highly potent neuraminidase (NA) inhibitors which, along with dimer 3, are being investigated as potential second generation inhaled therapies both for the treatment of influenza and for prophylactic use. They show outstanding activity in a 1 week mouse influenza prophylaxis assay, and compared with ZMV, high concentrations of 8 and 13 are found in rat lung tissue after 1 week. Retention of compounds in rat lung tissue correlated both with molecular weight (excluding 3 and 15) and with a capacity factor K‘ derived from immobilized artificial membrane (IAM) chromatography (including 3 and 15). Pharmacokinetic parameters for 3, 8 and 13 in rats show the compounds have short to moderate plasma half-lives, low clearances and low volumes of distribution. Dimer 3 shows NA inhibitory activity against N1 viruses including the recent highly pathogenic H5N1 A/Chicken/Vietnam/8/2004. In plaque reduction assays, 3, 8 and 13 show good to outstanding potency against a panel of nine flu A and B virus strains. Consistent with its shorter and more rigid linking group, dimer 8 has been successfully crystallized." @default.
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• W1968703453 date "2005-03-16" @default.
• W1968703453 modified "2023-10-08" @default.
• W1968703453 title "Dimeric Zanamivir Conjugates with Various Linking Groups Are Potent, Long-Lasting Inhibitors of Influenza Neuraminidase Including H5N1 Avian Influenza" @default.
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• W1968703453 doi "https://doi.org/10.1021/jm040891b" @default.
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• W1968703453 hasPublicationYear "2005" @default.
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