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Identification
NameEnoxacin
Accession NumberDB00467  (APRD00947)
TypeSmall Molecule
GroupsApproved
Description

A broad-spectrum 6-fluoronaphthyridinone antibacterial agent (fluoroquinolones) structurally related to nalidixic acid. [PubChem]

Structure
Thumb
Synonyms
1-Ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-1,8-naphthyridine-3-carboxylic acid
1-Ethyl-6-fluoro-4-oxo-7-piperazin-1-yl-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid
Enoxacin
Enoxacina
Énoxacine
Enoxacino
Enoxacinum
External Identifiers
  • AT 2266
  • CI 919
  • PD 107779
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
AlmitilNot Available
BactidanNot Available
ComprecinNot Available
EnoksetinNot Available
EnoxenNot Available
EnoxinNot Available
EnoxorPierre Fabre
EnoxorNot Available
EnroxilNot Available
FlumarkNot Available
GyramidNot Available
PenetrexNot Available
VinoneNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNII325OGW249P
CAS number74011-58-8
WeightAverage: 320.3189
Monoisotopic: 320.128468635
Chemical FormulaC15H17FN4O3
InChI KeyInChIKey=IDYZIJYBMGIQMJ-UHFFFAOYSA-N
InChI
InChI=1S/C15H17FN4O3/c1-2-19-8-10(15(22)23)12(21)9-7-11(16)14(18-13(9)19)20-5-3-17-4-6-20/h7-8,17H,2-6H2,1H3,(H,22,23)
IUPAC Name
1-ethyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid
SMILES
CCN1C=C(C(O)=O)C(=O)C2=CC(F)=C(N=C12)N1CCNCC1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as naphthyridine carboxylic acids and derivatives. These are compounds containing a naphthyridine moiety, where one of the ring atoms bears a carboxylic acid group.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassNaphthyridines
Sub ClassNaphthyridine carboxylic acids and derivatives
Direct ParentNaphthyridine carboxylic acids and derivatives
Alternative Parents
Substituents
  • Naphthyridine carboxylic acid
  • N-arylpiperazine
  • Pyridinylpiperazine
  • Fluoroquinolone
  • Pyridine carboxylic acid or derivatives
  • Pyridine carboxylic acid
  • Dialkylarylamine
  • Aminopyridine
  • Imidolactam
  • Pyridine
  • Piperazine
  • 1,4-diazinane
  • Aryl halide
  • Aryl fluoride
  • Heteroaromatic compound
  • Vinylogous amide
  • Tertiary amine
  • Azacycle
  • Secondary amine
  • Monocarboxylic acid or derivatives
  • Secondary aliphatic amine
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organofluoride
  • Organohalogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationFor the treatment of adults (≥18 years of age) with the following infections caused by susceptible strains of the designated microorganisms: (1) uncomplicated urethral or cervical gonorrhea due to Neisseria gonorrhoeae, (2) uncomplicated urinary tract infections (cystitis) due to Escherichia coli, Staphylococcus epidermidis, or Staphylococcus saprophyticus, and (3) complicated urinary tract infections due to Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Staphylococcus epidermidis, or Enterobacter cloacae.
PharmacodynamicsEnoxacin is a quinolone/fluoroquinolone antibiotic. Enoxacin is bactericidal and its mode of action depends on blocking of bacterial DNA replication by binding itself to an enzyme called DNA gyrase, which allows the untwisting required to replicate one DNA double helix into two. Enoxacin is a broad-spectrum antibiotic that is active against both Gram-positive and Gram-negative bacteria. Enoxacin may be active against pathogens resistant to drugs that act by different mechanisms.
Mechanism of actionEnoxacin exerts its bactericidal action via the inhibition of the essential bacterial enzyme DNA gyrase (DNA Topoisomerase II).
Related Articles
AbsorptionRapidly absorbed following oral administration, with an absolute oral bioavailability of approximately 90%.
Volume of distributionNot Available
Protein bindingEnoxacin is approximately 40% bound to plasma proteins in healthy subjects and is approximately 14% bound to plasma proteins in patients with impaired renal function.
Metabolism

Hepatic. Some isozymes of the cytochrome P-450 hepatic microsomal enzyme system are inhibited by enoxacin. After a single dose, greater than 40% was recovered in urine by 48 hours as unchanged drug.

Route of eliminationNot Available
Half lifePlasma half-life is 3 to 6 hours.
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Enteric bacteria and other eubacteria
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.995
Blood Brain Barrier-0.9659
Caco-2 permeable-0.8957
P-glycoprotein substrateSubstrate0.8683
P-glycoprotein inhibitor INon-inhibitor0.8978
P-glycoprotein inhibitor IINon-inhibitor0.8606
Renal organic cation transporterNon-inhibitor0.7736
CYP450 2C9 substrateNon-substrate0.8078
CYP450 2D6 substrateNon-substrate0.9115
CYP450 3A4 substrateNon-substrate0.7557
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.8862
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5351
Ames testAMES toxic0.9124
CarcinogenicityNon-carcinogens0.802
BiodegradationNot ready biodegradable1.0
Rat acute toxicity1.8383 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.6527
hERG inhibition (predictor II)Non-inhibitor0.5448
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Sanofi aventis us llc
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point220-224 °CPhysProp
water solubility3.43 g/LNot Available
logP-0.20SANGSTER (1994) (ION-CORRECT)
Predicted Properties
PropertyValueSource
Water Solubility1.09 mg/mLALOGPS
logP-0.97ALOGPS
logP-0.98ChemAxon
logS-2.5ALOGPS
pKa (Strongest Acidic)5.5ChemAxon
pKa (Strongest Basic)8.59ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area85.77 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity83.95 m3·mol-1ChemAxon
Polarizability31.63 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
References
Synthesis Reference

DrugSyn.org

US4359578
General ReferencesNot Available
External Links
ATC CodesJ01MA04
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (44.5 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)
Pharmacological action
yes
Actions
inhibitor
General Function:
Dna topoisomerase type ii (atp-hydrolyzing) activity
Specific Function:
DNA gyrase negatively supercoils closed circular double-stranded DNA in an ATP-dependent manner and also catalyzes the interconversion of other topological isomers of double-stranded DNA rings, including catenanes and knotted rings.
Gene Name:
gyrA
Uniprot ID:
P43700
Molecular Weight:
97817.145 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
  3. Yoshida H, Nakamura M, Bogaki M, Ito H, Kojima T, Hattori H, Nakamura S: Mechanism of action of quinolones against Escherichia coli DNA gyrase. Antimicrob Agents Chemother. 1993 Apr;37(4):839-45. [PubMed:8388200 ]
  4. Weisser J, Wiedemann B: Elimination of plasmids by enoxacin and ofloxacin at near inhibitory concentrations. J Antimicrob Chemother. 1986 Nov;18(5):575-83. [PubMed:3542924 ]
  5. Courtright JB, Turowski DA, Sonstein SA: Alteration of bacterial DNA structure, gene expression, and plasmid encoded antibiotic resistance following exposure to enoxacin. J Antimicrob Chemother. 1988 Feb;21 Suppl B:1-18. [PubMed:2834313 ]
  6. Neuman M: Clinical pharmacokinetics of the newer antibacterial 4-quinolones. Clin Pharmacokinet. 1988 Feb;14(2):96-121. [PubMed:3282749 ]
  7. Castora FJ, Vissering FF, Simpson MV: The effect of bacterial DNA gyrase inhibitors on DNA synthesis in mammalian mitochondria. Biochim Biophys Acta. 1983 Sep 9;740(4):417-27. [PubMed:6309236 ]
Kind
Protein
Organism
Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)
Pharmacological action
yes
Actions
inhibitor
General Function:
Dna topoisomerase type ii (atp-hydrolyzing) activity
Specific Function:
Topoisomerase IV is essential for chromosome segregation. It relaxes supercoiled DNA. Performs the decatenation events required during the replication of a circular DNA molecule.
Gene Name:
parC
Uniprot ID:
P43702
Molecular Weight:
83366.24 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
  3. Neuman M: Clinical pharmacokinetics of the newer antibacterial 4-quinolones. Clin Pharmacokinet. 1988 Feb;14(2):96-121. [PubMed:3282749 ]
  4. Takahashi H, Hayakawa I, Akimoto T: [The history of the development and changes of quinolone antibacterial agents]. Yakushigaku Zasshi. 2003;38(2):161-79. [PubMed:15143768 ]
Kind
Protein
Organism
Human
Pharmacological action
no
Actions
inhibitor
General Function:
Ubiquitin binding
Specific Function:
Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks. Essential during mitosis and meiosis for proper segregation of daughter chromosomes. May play a role in regulating the period length of ARNTL/BMAL1 transcriptional oscillation (By similarity).
Gene Name:
TOP2A
Uniprot ID:
P11388
Molecular Weight:
174383.88 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  2. Maki T, Hirono I, Kondo H, Aoki T: Drug resistance mechanism of the fish-pathogenic bacterium Lactococcus garvieae. J Fish Dis. 2008 Jun;31(6):461-8. doi: 10.1111/j.1365-2761.2008.00927.x. [PubMed:18471102 ]
  3. Snyder RD, Cooper CS: Photogenotoxicity of fluoroquinolones in Chinese hamster V79 cells: dependency on active topoisomerase II. Photochem Photobiol. 1999 Mar;69(3):288-93. [PubMed:10089819 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N...
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular Weight:
58293.76 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23