Ozenoxacin

Ozenoxacin
Clinical data
Pronunciationoz en ox' a sin
Trade namesOzanex; Xepi
AHFS/Drugs.comMonograph
MedlinePlusa618010
License data
Routes of
administration		Topical
ATC code
Legal status
Legal status
Identifiers
  • 1-Cyclopropyl-8-methyl-7-[5-methyl-6-(methylamino)-3-pyridinyl]-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC21H21N3O3
Molar mass363.417 g·mol−1
3D model (JSmol)
  • O=C\3c1c(c(c(cc1)c2cc(c(nc2)NC)C)C)N(/C=C/3C(=O)O)C4CC4
  • InChI=1S/C21H21N3O3/c1-11-8-13(9-23-20(11)22-3)15-6-7-16-18(12(15)2)24(14-4-5-14)10-17(19(16)25)21(26)27/h6-10,14H,4-5H2,1-3H3,(H,22,23)(H,26,27)
  • Key:XPIJWUTXQAGSLK-UHFFFAOYSA-N

Ozenoxacin, sold under the brand names Ozanex and Xepi, is a quinolone antibiotic used for the treatment of impetigo.[4] A 1% topical cream is approved for treatment of impetigo in Canada[5] and in the United States.[6][7]

Ozenoxacin is active against some bacteria that have developed resistance to fluoroquinolone antibiotics.[8]

Mechanism of action

Like other quinolone antibiotics, ozenoxacin targets DNA gyrase and topoisomerase IV.[9]

Its activity against bacteria with fluoroquinolone resistance is attributed to its evasion of bacterial efflux pumps.[8]

Chemistry

Synthesis

Ozenoxacin is synthesized by the Pd-catalyzed cross-coupling of a bromoquinolone and a pyridyl tributylstannane (Stille coupling).[10][11]

Synthesis of ozenoxacin

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).

References

  1. ^ "Skin health". Health Canada. 9 May 2018. Retrieved 13 April 2024.
  2. ^ "Xepi- ozenoxacin cream". DailyMed. 30 January 2020. Retrieved 13 October 2020.
  3. ^ "List of nationally authorised medicinal products" (PDF). Retrieved 2024-05-20.
  4. ^ "Ozenoxacin". PubChem. U.S. National Library of Medicine. Retrieved 2019-01-10.
  5. ^ "Cipher Pharmaceuticals Receives Health Canada Approval of Ozanex (ozenoxacin cream 1%)" (Press release). Cipher Pharmaceuticals Inc.
  6. ^ "Medimetriks Pharmaceuticals, Inc. Receives FDA Approval for Xepi (ozenoxacin) Cream, 1%, a Novel Topical Antibiotic for Impetigo" (Press release). Medimetriks Pharmaceuticals, Inc. – via PRNewswire.
  7. ^ "Xepi (ozenoxacin) Cream". U.S. Food and Drug Administration (FDA). 18 January 2018. Retrieved 13 October 2020.
  8. ^ a b López Y, Tato M, Espinal P, Garcia-Alonso F, Gargallo-Viola D, Cantón R, Vila J (December 2013). "In vitro activity of Ozenoxacin against quinolone-susceptible and quinolone-resistant gram-positive bacteria". Antimicrobial Agents and Chemotherapy. 57 (12): 6389–6392. doi:10.1128/AAC.01509-13. PMC 3837899. PMID 24080666.
  9. ^ Vila J, Hebert AA, Torrelo A, López Y, Tato M, García-Castillo M, Cantón R (March 2019). "Ozenoxacin: a review of preclinical and clinical efficacy". Expert Review of Anti-Infective Therapy. 17 (3): 159–168. doi:10.1080/14787210.2019.1573671. hdl:2445/130535. PMID 30686133. S2CID 205850659.
  10. ^ US 6335447, Hayashi K, Kito T, Mitsuyama J, Yamakawa T, Kuroda H, Kawafuchi H, "Quinolonecarboxylic acid derivatives or salts thereof", issued 2002-01-01, assigned to Toyama Chemical Co Ltd 
  11. ^ Flick AC, Ding HX, Leverett CA, Kyne RE, Liu KK, Fink SJ, O'Donnell CJ (August 2017). "Synthetic Approaches to the New Drugs Approved During 2015". Journal of Medicinal Chemistry. 60 (15): 6480–6515. doi:10.1021/acs.jmedchem.7b00010. PMID 28421763.