Influenza virus neuraminidase inhibitors

Gubareva LV, Kaiser L, and Hayden FG. Influenza virus neuraminidase inhibitors. Lancet 2000 355 827-835. 

Colman PM. Zanamivir an influenza virus neuraminidase inhibitor. Expert Rev Anti Infect Ther. 2005 3 191-199. 

P. M. Colman Design and antiviral properties of influenza virus neuraminidase inhibitors... 

In a structure-based drug-discovery programme in the field of influenza virus neuraminidase inhibitors, researchers at BioCryst Pharmaceuticals discovered aminocarbafuranose sialyl mimetic 89 as a very potent candidate against influenza A and B viruses [17]. To arrive at this highly substituted compound in a non-racemic format, the viable route of Scheme 14 was executed. 

Drug Discovery Today 7 25-27 Li AP (2004) In vitro approaches to evaluate ADMET drug properties. Curr Top Med Chem 4 701-706 Li W, Escarpe PA, Eisenberg EJ et al. (1998) Identification of GS 4104 as an orally bioavailable prodrug of the influenza virus neuraminidase inhibitor GS 4071. Antimicrobial Agents and Chemotherapy 42 647-653 Los LE, Welsh DA, Herold EG et al. (1996) Gender differences in toxicokinetics, liver metabolism, and plasma esterase activity observations from a chronic (27-week) toxicity study of enalapril/diltiazem combinations in rats. Drug Metab Dispos 24 28-33... 

Croft A 2000 Malaria prevention in travellers. British Medical Journal 321 154-160 Flexner C 1998 HIV-protease inhibitors. New England Journal of Medicine 338 1281-1292 Gilden D H et al 2000 Neurological complications of the reactivation of varicella-zoster virus. New England Journal of Medicine 342 635-645 Gubareva L V, Kaiser L, Hayden F G 2000 Influenza virus neuraminidase inhibitors. Lancet 355 827-835... 

A fine example of structure-based drug design has been reported for the design of an influenza virus neuraminidase inhibitor (see Scheme 11). Neuraminidase is an enzyme expressed on the surface of influenza virions and it is thought to be important for the successful release of progeny. Inhibition of... 

Steindl, T., Langer, T. Influenza virus neuraminidase inhibitors generation and comparison of structure-based and common feature pharmacophore hypotheses and their application in virtual screening. J. Chem. Inform. Comput. Sci. 2004, 44, 1849-1856. 

Mendel DB, Tai CY, Escarpe PA, Li W, Sidwell RW, Huffman JH, Sweet C, Jakeman KJ, Merson J, Lacy SA, Lew W, Williams M A, Zhang L, Chen MS, Bischofberger N, Kim CU. Oral administration of a prodrug of the influenza virus neuraminidase inhibitor GS 4071 protects mice and ferrets against influenza infection. Antimicrob Agents Chemother 1998 42 640-646. 

The influenza virus neuraminidase inhibitor GGl67 labeled with C in the guanidine group has been synthesized from [ C] cyanogen bromide (Westerberg et al. 1996) as shown in O Fig. 41.20. 

DRUGS ACTIVE AGAINST INFLUENZA VIRUSES NEURAMINIDASE INHIBITORS [SED-15, 2436 SEDA-31, 489 SEDA-32, 544 SEDA-33, 601 ... 

Identification of GS 4104 as an orally bioavailable prodrug of the influenza virus neuraminidase inhibitor GS 4071. Antimicrobial Agents and Chemotherapy,... 

Due to the transfer mechanism of TcTS analogous to those of sialidases [25] the prototype of sialidase inhibitors Neu5Ac2en 99 [57] was tested. Compound 99 as well as the potent influenza virus neuraminidase inhibitors zanamivir (Relenza, 100) and the active form of oseltamivir (Tamiflu, 101) with analogous structures of transition state were also of interest as potential inhibitors of TcTS. However, as determined for 99 the TcTS activity was inhibited with only Ki = 12.29 mM (Fig. 15) [33]. 

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