Discovery and Development of GS 4104 (oseltamivir) An Orally Active Influenza Neuraminidase Inhibitor

Willard      Lew; Xiaowu      Chen; Choung   U.   Kim

Abstract

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.

Keywords: GS 4104 oseltamivir, active influenza neuraminidase inhibitors, X ray crystal structures, influenza virus neuraminidase, sialic acid based, inhibitor design, structure activity relationship, carbocyclic inhibitors, isosteres, carbocyclic influenza neuramindase inhibitors