Anti-influenza A virus agents

Domino reactions are also used in the development of new and potent pharmaceuticals, which is an important target in organic synthesis. The following example by Katoh and coworkers presents an impressive approach to the tetracyclic core structure of the novel anti-influenza A virus agent, stachyflin (1-152), using as key feature a new Lewis acid-induced domino epoxide-opening/rearrangement/cy-... 

Watanabe K, Sakurai J, Abe H, Katoh T. Total synthesis of (+)-stachyflin a potential anti-influenza A virus agent. Chem. Commun. 2010 46(23) 4055 57. 

Burlington DB, Meiklejohn G, Mostow SR. Anti-influenza A virus activity of amantadine hydrochloride and rimantadine hydrochloride in ferret tracheal ciliated epithelium. Antimicrob Agents Chemother 1982 21 794-799. 

Influenza A viruses cause severe infections in the respiratory system and are responsible for seasonal epidemics and sporadic pandemics. The primary method for prevention is through vaccination but vaccine production by current methods cannot be carried out in time to stop the progress of a new strain of the influenza virus. Therefore, effective antiviral agents are used for prophylactic and therapeutic treatments. Among several viral molecular targets for anti-influenza drugs, the surface glycoprotein neuraminidase appears particularly attractive. Selective inhibitors of this enzyme have been developed and two of which, oseltamivir phosphate 18 (Tamiflu ) " and zanamivir 19 (Relenza ), have been approved for human use (Scheme 6). 

As a result of the emergence of the extremely aggressive avian H5N1 influenza virus, the likelihood of a human influenza pandemic and the possible socioeconomic impact is now of major concern. In the absence of strain-independent anti-influenza drugs, there has been significant effort worldwide over the years in the quest for the discovery of novel therapeutic agents against all types of influenza. 

Bantia S, Parker CD, Ananth SL, Horn LL, Andries K, Chand P, Kotian PL, Dehghani A, El Kattan Y, Lin T, Hutchison TL, Montgomery JA, Kellog DL, Babu YS (2001) Comparison of the anti-influenza virus activity of RWJ-270201 with those of oseltamivir and zanamivir. Antimicrob Agents Chemother 45 1162-1167... 

Yamashita M, Ohno A, TomozawaT, Yoshida S (2003) R-118958, a unique anti-influenza agenf. I. A prodrug form of R-125489, a novel inhibitor of influenza virus neuraminidase. In 43rd in-tersdence conference on antimicrobial agents and chemotherapy, Chicago, USA, Sept 14-17, Poster F-1829... 

Because of the essential role of sialidase in influenza virus replication and the highly conserved enzyme active-site in influenza viruses A and B, most interest has been focused on the development of selective inhibitors of this enzyme.10 This chapter discusses the tremendous progress that has been made in the discovery of this new class of anti-influenza agents, in addition to some background information to understand the fundamental role of influenza. 

D. F. Smee, J. H. Huffman, A. C. Morrison, D. L. Barnard, and R. W. Sidwell, Cyclopentane neuraminidase inhibitors with potent in vitro anti-influenza virus activities, Antimicrob. Agents Chemother., 45 (2001) 743-748. 

Several excellent articles describing various aspects of influenza virus, both with respect to the virus itself as well as approaches towards the development of anti-influenza agents, have been published in recent years [4-16]. In view of the comprehensive nature of these reports it is the aim of this account, apart from providing the background information necessary to a fundamental understanding of influenza, to focus on advances in the development of influenza virus sialidase inhibitors over the last decade. ... 

Since haemagglutinin is involved in the adhesion of influenza virus to epithelial cells, it is an attractive target for therapeutic intervention. The design and synthesis of potential inhibitors of haemagglutinin has been reviewed elsewhere [5, 7, 14, 17, 33, 34] and, apart from a brief discussion of the general approaches employed towards such anti-influenza agents, is outside the scope of this article. 

S. (2009) CS-8958, a prodrug of the new neuraminidase inhibitor R-125489, shows long-acting anti-influenza virus activity. Antimicrobial Agents and Chemotherapy, 53, 186-192. 

The toxicity of starfishes may be derived from the saponins. The biological activities of these compounds were reported, including haemolytic properties, and antitumour [104] and antibacterial activities [105]. Inhibition activities for influenza virus multiplication, and anti-inflammatory activity towards contraction of the rat phrenic nerve diaphragm preparation, were also reported [106]. Saponins are chemical defence agents in starfishes, and they also induce escape reactions in bivalve molluscs [107]. It is of interest to note that the sperm agglutination substance in the egg jelly of starfish is similar to asterosaponin A [108]. 

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