Discovery and development of GS 4104 (oseltamivir): an orally active influenza neuraminidase inhibitor.
Rational drug design utilizing available X-ray crystal structures of sialic acid analogues bound to the active site of influenza virus neuraminidase has led to the discovery of a series of potent carbocyclic influenza neuraminidase inhibitors. From this series, GS 4104 (oseltamivir, TAMIFLU ) has emerged as a promising antiviral for the treatment and prophylaxis of human influenza infection. This article will summarize the design, discovery, and development of oseltamivir as an oral therapeutic to treat influenza infection.
Lew
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Gilead Sciences Inc., 333 Lakeside Drive, Foster City, California, 94404, USA.
Chen
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Kim
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D000284:Administration, Oral; D000588:Amines / Q000494:pharmacology*; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D009975:Orthomyxoviridae / Q000187:drug effects* / Q000201:enzymology; D053139:Oseltamivir; D013329:Structure-Activity Relationship
D000588:Amines; D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D053139:Oseltamivir; D009439:Neuraminidase