Recent advances in the discovery and synthesis of neuraminidase inhibitors

Abstract

The influenza virus neuraminidase (NA) is important in the pathogenesis of infection and, thus, is an attractive target for agents used in the treatment and prophylaxis of influenza. Two drugs discovered from the structure-based drug design of neuraminidase inhibitors, zanamivir and oseltamivir phosphate, were approved by the FDA in 1999. Both drugs are effective in the control of influenza infections in humans. As pandemic is a worldwide outbreak, there is still continuous interest in this disease, and 15 patents on neuraminidase inhibitors have appeared in the literature since the last review in November 2001. This article updates the patent literature since then. As syntheses were not given in the previous review article, the details of the synthesis of both drugs, zanamivir and oseltamivir phosphate, and of other potent inhibitors, (-)-(1S,2S,3R,4R)-3-[(1S)-1-(acetylamino)-2-ethylbutyl]-4-{[amino(imino)methyl]amino}-2-hydroxycyclopentanecarboxylic acid (peramivir, BCX-1812 or RWJ-270201), (-)-(2R,4S,5R)-5-[(1R,2S)-1-(acetylamino)-2-methoxy-2-methylpentyl]-4-[(1Z)-prop-1-enyl]pyrrolidine-2-carboxylic acid (ABT-675) and Biota’s polymeric compounds, are also revealed in this article.

Keywords::

• ABT-675
• BCX-1812
• neuraminidase inhibitor
• oseltamivir
• zanamivir