Ozenoxacin, sold under the brand names Ozanex and Xepi, is a quinolone antibiotic used for the treatment of impetigo. A 1% topical cream is approved for treatment of impetigo in Canada and in the United States.
Ozenoxacin is active against some bacteria that have developed resistance to fluoroquinolone antibiotics.
Mechanism of action
Like other quinolone antibiotics, ozenoxacin targets DNA gyrase and topoisomerase IV.
Its activity against bacteria with fluoroquinolone resistance is attributed to its evasion of bacterial efflux pumps.
Chemistry
Synthesis
Ozenoxacin is synthesized by the Pd-catalyzed cross-coupling of a bromoquinolone and a pyridyl tributylstannane (Stille coupling).
The pyridyl tributylstannane is synthesized from the corresponding dihalopyridine. This is achieved through a sequence of nucleophilic aromatic substitution with methylamine, which is protected as the acetamide using acetic anhydride and this is converted to the organostannane through a Pd-catalyzed stannylation with bis(tributyltin).
The bromoquinolone is made from the N-cyclopropyl aniline and diethyl ethoxymethylenemalonate, which react through a Michael addition, followed by elimination of the ethoxy group and then a Friedel-Crafts acylation at elevated temperature. The N-cyclopropyl aniline is prepared by a Pd-catalyzed cross coupling of 2,6-dibromotoluene and cyclopropylamine (Buchwald-Hartwig coupling).
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