Ozenoxacin

Last updated
Ozenoxacin
Ozenoxacin.svg
Clinical data
Pronunciationoz en ox' a sin
Trade names Ozanex; Xepi
AHFS/Drugs.com Monograph
MedlinePlus a618010
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
Formula C21H21N3O3
Molar mass 363.417 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. [3] A 1% topical cream is approved for treatment of impetigo in Canada [4] and in the United States. [5] [6]

Contents

Ozenoxacin is active against some bacteria that have developed resistance to fluoroquinolone antibiotics. [7]

Mechanism of Action

Like other quinolone antibiotics, ozenoxacin targets DNA gyrase and topoisomerase IV. [8]

Its activity against bacteria with fluoroquinolone resistance is attributed to its evasion of bacterial efflux pumps. [7]

Chemistry

Synthesis

Synthesis of Ozenoxacin Ozenoxacin synthesis.png
Synthesis of Ozenoxacin

Ozenoxacin is synthesized by the Pd-catalyzed cross-coupling of a bromoquinolone and a pyridyl tributylstannane (Stille coupling). [9] [10]

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).

Related Research Articles

<span class="mw-page-title-main">Ciprofloxacin</span> Fluoroquinolone antibiotic

Ciprofloxacin is a fluoroquinolone antibiotic used to treat a number of bacterial infections. This includes bone and joint infections, intra-abdominal infections, certain types of infectious diarrhea, respiratory tract infections, skin infections, typhoid fever, and urinary tract infections, among others. For some infections it is used in addition to other antibiotics. It can be taken by mouth, as eye drops, as ear drops, or intravenously.

<span class="mw-page-title-main">Levofloxacin</span> Antibiotic

Levofloxacin, sold under the brand name Levaquin among others, is an antibiotic medication. It is used to treat a number of bacterial infections including acute bacterial sinusitis, pneumonia, H. pylori, urinary tract infections, chronic prostatitis, and some types of gastroenteritis. Along with other antibiotics it may be used to treat tuberculosis, meningitis, or pelvic inflammatory disease. Use is generally recommended only when other options are not available. It is available by mouth, intravenously, and in eye drop form.

<span class="mw-page-title-main">Ofloxacin</span> Antibiotic to treat bacterial infections

Ofloxacin is a quinolone antibiotic useful for the treatment of a number of bacterial infections. When taken by mouth or injection into a vein, these include pneumonia, cellulitis, urinary tract infections, prostatitis, plague, and certain types of infectious diarrhea. Other uses, along with other medications, include treating multidrug resistant tuberculosis. An eye drop may be used for a superficial bacterial infection of the eye and an ear drop may be used for otitis media when a hole in the ear drum is present.

<span class="mw-page-title-main">Nalidixic acid</span> First of the synthetic quinolone antibiotics

Nalidixic acid is the first of the synthetic quinolone antibiotics.

<span class="mw-page-title-main">Norfloxacin</span> Chemical compound, antibiotic

Norfloxacin, sold under the brand name Noroxin among others, is an antibiotic that belongs to the class of fluoroquinolone antibiotics. It is used to treat urinary tract infections, gynecological infections, inflammation of the prostate gland, gonorrhea and bladder infection. Eye drops were approved for use in children older than one year of age.

<span class="mw-page-title-main">Moxifloxacin</span> Antibiotic

Moxifloxacin is an antibiotic, used to treat bacterial infections, including pneumonia, conjunctivitis, endocarditis, tuberculosis, and sinusitis. It can be given by mouth, by injection into a vein, and as an eye drop.

<span class="mw-page-title-main">Gemifloxacin</span> Chemical to treat chronic bronchitis

Gemifloxacin mesylate is an oral broad-spectrum quinolone antibacterial agent used in the treatment of acute bacterial exacerbation of chronic bronchitis and mild-to-moderate pneumonia. Vansen Pharma Inc. has licensed the active ingredient from LG Life Sciences of Korea.

<span class="mw-page-title-main">Cinoxacin</span> Chemical compound

Cinoxacin is a quinolone antibiotic that has been discontinued in the U.K. as well the United States, both as a branded drug or a generic. The marketing authorization of cinoxacin has been suspended throughout the EU.

<span class="mw-page-title-main">Rosoxacin</span> Antibiotic

Rosoxacin is a quinolone antibiotic indicated for the treatment of urinary tract infections and certain sexually transmitted diseases. Rosoxacin is not available in the United States.

<span class="mw-page-title-main">Fleroxacin</span> Chemical compound

Fleroxacin is a quinolone antibiotic. It is sold under the brand names Quinodis and Megalocin.

<span class="mw-page-title-main">Flumequine</span> Chemical compound

Flumequine is a synthetic fluoroquinolone antibiotic used to treat bacterial infections. It is a first-generation fluoroquinolone antibacterial that has been removed from clinical use and is no longer being marketed. The marketing authorization of flumequine has been suspended throughout the EU. It kills bacteria by interfering with the enzymes that cause DNA to unwind and duplicate. Flumequine was used in veterinarian medicine for the treatment of enteric infections, as well as to treat cattle, swine, chickens, and fish, but only in a limited number of countries. It was occasionally used in France to treat urinary tract infections under the trade name Apurone. However this was a limited indication because only minimal serum levels were achieved.

<span class="mw-page-title-main">Prulifloxacin</span> Chemical compound

Prulifloxacin is an older synthetic antibiotic of the fluoroquinolone class undergoing clinical trials prior to a possible NDA submission to the U.S. Food and Drug Administration (FDA). It is a prodrug which is metabolized in the body to the active compound ulifloxacin. It was developed over two decades ago by Nippon Shinyaku Co. and was patented in Japan in 1987 and in the United States in 1989.

<span class="mw-page-title-main">Nadifloxacin</span> Chemical compound

Nadifloxacin is a topical fluoroquinolone antibiotic for the treatment of acne vulgaris. It is also used to treat bacterial skin infections.

<span class="mw-page-title-main">Difloxacin</span> Chemical compound

Difloxacin (INN), marketed under the trade name Dicural, is a second-generation, synthetic fluoroquinolone antibiotic used in veterinary medicine. It has broad-spectrum, concentration dependent, bactericidal activity; however, its efficacy is not as good as enrofloxacin or pradofloxacin.

<span class="mw-page-title-main">Balofloxacin</span> Chemical compound

Balofloxacin (INN) is a fluoroquinolone antibiotic. It is sold under the brand name Q-Roxin in Korea, and under various names in India. It is not approved by the FDA for use in the United States.

<span class="mw-page-title-main">Delafloxacin</span> Chemical compound

Delafloxacin sold under the brand name Baxdela among others, is a fluoroquinolone antibiotic used to treat acute bacterial skin and skin structure infections.

<span class="mw-page-title-main">Quinolone antibiotic</span> Class of antibacterial drugs, subgroup of quinolones

Quinolone antibiotics constitute a large group of broad-spectrum bacteriocidals that share a bicyclic core structure related to the substance 4-quinolone. They are used in human and veterinary medicine to treat bacterial infections, as well as in animal husbandry, specifically poultry production.

Antimicrobials destroy bacteria, viruses, fungi, algae, and other microbes. The cells of bacteria (prokaryotes), such as salmonella, differ from those of higher-level organisms (eukaryotes), such as fish. Antibiotics are chemicals designed to either kill or inhibit the growth of pathogenic bacteria while exploiting the differences between prokaryotes and eukaryotes in order to make them relatively harmless in higher-level organisms. Antibiotics are constructed to act in one of three ways: by disrupting cell membranes of bacteria, by impeding DNA or protein synthesis, or by hampering the activity of certain enzymes unique to bacteria.

<span class="mw-page-title-main">Zabofloxacin</span> Chemical compound

Zabofloxacin (DW-224a) is an investigational fluoroquinolone antibiotic for multidrug-resistant infections due to Gram-positive bacteria. It also has activity against Neisseria gonorrhoeae including strains that are resistant to other quinolone antibiotics.

<span class="mw-page-title-main">Finafloxacin</span> Chemical compound

Finafloxacin (Xtoro) is a fluoroquinolone antibiotic. In the United States, it is approved by the Food and Drug Administration to treat acute otitis externa caused by the bacteria Pseudomonas aeruginosa and Staphylococcus aureus.

References

  1. "Xepi- ozenoxacin cream". DailyMed. 30 January 2020. Retrieved 13 October 2020.
  2. https://www.ema.europa.eu/documents/psusa/ozenoxacin-list-nationally-authorised-medicinal-products-psusa/00010651/202205_en.pdf [ bare URL PDF ]
  3. "Ozenoxacin". PubChem. U.S. National Library of Medicine. Retrieved 2019-01-10.
  4. "Cipher Pharmaceuticals Receives Health Canada Approval of Ozanex (ozenoxacin cream 1%)" (Press release). Cipher Pharmaceuticals Inc.
  5. "Medimetriks Pharmaceuticals, Inc. Receives FDA Approval for Xepi (ozenoxacin) Cream, 1%, a Novel Topical Antibiotic for Impetigo" (Press release). Medimetriks Pharmaceuticals, Inc. via PRNewswire.
  6. "Xepi (ozenoxacin) Cream". U.S. Food and Drug Administration (FDA). 18 January 2018. Retrieved 13 October 2020.
  7. 1 2 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.
  8. 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.
  9. 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
  10. 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.