At physiological pH (7.4),<unk>  exists in an uncharged state. It is moderately water-soluble (approximately 3 mg/mL), with a logP of 0.55. Numbered structure of<unk> , showing the pharmacophore required for good activity (in blue) and desirable structural features (in orange).|alt=Skeletal formula of N-{(5S)-3-3-fluoro-4-(morpholin-4-yl)phenyl-2-oxo-1,3-oxazolidin-5-ylmethyl}acetamide, highlighting the morpholino and fluoro groups in orange, with the rest in blue. The carbon atoms of the parent chain are numbered. The oxazolidinone pharmacophore—the chemical "template" essential for antimicrobial activity—consists of a 1,3-oxazolidin-2-one moiety with an aryl group at position 3 and an S-methyl group, with another substituent attached to it, at position 5 (the R-enantiomers of all oxazolidinones are devoid of antibiotic properties). In addition to this essential core,<unk>  also contains several structural characteristics that improve its effectiveness and safety. An acetamide substituent on the 5-methyl group is the best choice in terms of antibacterial efficacy, and is used in all of the more active oxazolidinones developed thus far; in fact, straying too far from an acetamide group at this position makes the drug lose its antimicrobial power, although weak to moderate activity is maintained when some isosteric groups are used. A fluorine atom at the 3′ position practically doubles in vitro and in vivo activity, and the electron-donating nitrogen atom in the morpholine ring helps maintain high antibiotic potency and an acceptable safety profile. The anticoagulant rivaroxaban (Xarelto) bears a striking structural similarity to<unk> ; both drugs share the oxazolidinone pharmacophore, differing in only three areas (an extra ketone and chlorothiophene, and missing the fluorine atom). However this similarity appears to carry no clinical significance. Synthesis<unk>  is a completely synthetic drug: it does not occur in nature (unlike erythromycin and many other antibiotics) and was not developed by building upon a naturally occurring skeleton (unlike most beta-lactams, which are semisynthetic). Many approaches are available for oxazolidinone synthesis, and several routes for the synthesis of<unk>  have been reported in the chemistry literature. Despite good yields, the original method (developed by Upjohn for pilot plant-scale production of<unk>  and eperezolid) is lengthy, requires the use of expensive chemicals—such as palladium on carbon and the highly sensitive reagents methanesulfonyl chloride and n-butyllithium—and needs low-temperature conditions. Much of the high cost of<unk>  has been attributed to the expense of its synthesis. A somewhat more concise and cost-effective route better suited to large-scale production was patented by Upjohn in 1998. Later syntheses have included an "atom-economical" method starting from D-mannitol, developed by Indian pharmaceutical company Dr. Reddy's and reported in 1999, and a route starting from (S)-glyceraldehyde acetonide (prepared from ascorbic acid), developed by a team of researchers from Hunan Normal University in Changsha, Hunan, China. On 25 June 2008, during the 12th Annual Green Chemistry and Engineering Conference in New York, Pfizer reported the development of their "second-generation" synthesis of<unk> : a convergent, green synthesis starting from (S)-epichlorohydrin, with higher yield and a 56% reduction in total waste.
Linezolid
Meropenem
Teicoplanin
Vancomycin
Resistin
Daptomycin
Ertapenem
Colistin