Linezolid Zyvox

Structural Formula Ball-and-Stick Model

Space-filling Model

: Carbon = Hydrogen M = Oxygen

Fluorine A = Nitrogen

Year of discovery: 1993 (by Steven J. Brickner at Upjohn); Year of introduction: 2000 (as Zyvox by Pharmacia, now Pfizer); Drug category: Oxazoiidinone; Main uses: For the treatment of serious Gram-positive bacterial infections that are resistant to all other known antibiotics; Related drugs: AZD2563 (under development by AstraZeneca).

Linezolid, a completely synthetic antibiotic of the oxazoiidinone class, was discovered in 1993 by S.J. Brickner and coworkers at Upjohn. Members of this class of drugs share a common structural element, a five-mem-bered oxazoiidinone ring (highlighted in red). The antibiotic properties of oxazolidinones were first recognized in 1984 at DuPont during the investigation of substances (e.g., DuP-721, see structure below) for the treatment of plant diseases caused by bacterial and fungal pathogens.1 Subsequent animal studies, however, revealed serious toxicity associated with many of these compounds. In the late 1980s Brickner initiated a search for oxazolidinones that are both potent and safe for human use. This effort led to the discovery of eperezolid and linezolid. Extensive studies of the relationship between structure, activity and toxicity revealed that linezolid possesses the best pharmacokinetic and safety profile and also high potency against resistant Grampositive bacteria.2 It was the first novel antibiotic in 40 years, since all the new antibiotics between 1960 and 2000 were derived simply by chemical modification of members of previously known classes.

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