Zanamivir chemistry

A series of fourteen 4-triazole-modified Zanamivir analogues were synthesized from the 4-azido-4-deoxy-Neu5Ac2en derivative using click chemistry, and their inhibitory potencies against influenza virus sialidase were determined. These modifications were not that successful as 33-35 demonstrated only 6-40% protective rate at a concentration of 50 pM against the virus infection compared to Zanamivir which shows 86% at the same concentration. The best result was obtained for compound 36, which showed a protective rate of >61%.76... 

Much of the chemistry devoted to side-chain modified zanamivir analogues has been driven by a desire to prepare structurally simpler derivatives, especially from the viewpoint of easier chemical syntheses. Replacement of the glycerol side-chain of zanamivir with an achiral ether substituent has... 

Of all the influenza virus sialidase inhibitors based on zanamivir reported to date, the most promising compounds are those which contain a carbocyc-lic ring in place of the dihydropyran ring. Early work in this regard involved the use of Diels-Alder chemistry to ultimately provide access to the side-... 

CHEMISTRY AND ANTIVIRAL ACTIVITY Zanamivir (4-guanidino-2,4-dideoxy-2, 3-dehydro-/V-acetyl neuraminic acid) is a siaMc acid analog that potently and specifically inhibits the neuraminidases of influenza A and B viruses. Depending on the strain, zanamivir competitively inhibits influenza neuraminidase activity but affects neuraminidases from other pathogens and mammalian sources only at much higher concentrations. Zanamivir inhibits in vitro replication of influenza A and B viruses, including amantadine- and rimantadine-resistant strains and several oseltamivir-resistant variants. 

Smith, P.W., SoUis, S.L., Howes, P.D., Cherry, PC., Starkey, I.D., Cobley, K.N., Weston, H., et al. 1998. Dihydropyrancarboxamides related to zanamivir A new series of inhibitors of influenza virus sialidases. 1. Discovery, synthesis, biological activity, and structure-activity relationships of 4-guanidino- and 4-amino-4/f-pyran-6-carboxamides. Journal of Medicinal Chemistry 41(6) 787-797. 

S. -Y., Cheng, Y.-ST., Fang, J.-M., and Wong, C.-R (2009) Synergistic effect of zanamivir porphyrin conjugates on inhibition of neuraminidase and inactivation of influenza virus. Jourrml of Medicinal Chemistry, 52,4903 4910. 

A rare example of the use of FVP in carbohydrate chemistry is provided by the high-yielding elimination of acetic acid from the tetrahydropyran 362 to give the 3,4-dihydro-2H-pyran 363, an intermediate in the synthesis of the influenza dmg Relenza (zanamivir) (Scheme 72 2009JOC4357). 

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