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Identification
NameCinoxacin
Accession NumberDB00827  (APRD00873)
Typesmall molecule
Groupsapproved, withdrawn
Description

Synthetic antimicrobial related to oxolinic acid and nalidixic acid and used in urinary tract infections. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
CinoxacinGermanINN
CinoxacineFrenchINN
CinoxacinoSpanishINN
CinoxacinumLatinINN
SaltsNot Available
Brand names
NameCompany
CinobacOclassen
MeciconChung Mei
TatsulexinTatsumi Kagaku
UrocinoxBioHealth Pharmaceuticals
Brand mixturesNot Available
CategoriesNot Available
CAS number28657-80-9
WeightAverage: 262.2182
Monoisotopic: 262.05897144
Chemical FormulaC12H10N2O5
InChI KeyVDUWPHTZYNWKRN-UHFFFAOYSA-N
InChI
InChI=1S/C12H10N2O5/c1-2-14-7-4-9-8(18-5-19-9)3-6(7)11(15)10(13-14)12(16)17/h3-4H,2,5H2,1H3,(H,16,17)
IUPAC Name
1-ethyl-4-oxo-1H,4H,7H-[1,3]dioxolo[4,5-g]cinnoline-3-carboxylic acid
SMILES
CCN1N=C(C(O)=O)C(=O)C2=CC3=C(OCO3)C=C12
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassNaphthyridines
SubclassCinnolines
Direct parentCinnolines
Alternative parentsBenzodioxoles; Alkyl Aryl Ethers; Benzene and Substituted Derivatives; Pyridazines and Derivatives; Carboxylic Acids; Enolates; Polyamines; Acetals
Substituentsalkyl aryl ether; pyridazine; benzene; acetal; enolate; carboxylic acid derivative; ether; carboxylic acid; polyamine; amine; organonitrogen compound
Classification descriptionThis compound belongs to the cinnolines. These are organic aromatic compounds containing a benzene fused to a pyridazine ring.
Pharmacology
IndicationFor the treatment of initial and recurrent urinary tract infections in adults caused by the following susceptible microorganisms: Escherichia coli, Proteus mirabilis, Proteus vulgaris, Klebsiella species (including K. pneumoniae), and Enterobacter species.
PharmacodynamicsCinoxacin is a synthetic antibacterial agent with in vitro activity against many gram-negative aerobic bacteria, particularly strains of the Enterobacteriaceae family. Cinoxacin inhibits bacterial deoxyribonucleic acid (DNA) synthesis, is bactericidal, and is active over the entire urinary pH range. Cross resistance with nalidixic acid has been demonstrated.
Mechanism of actionEvidence exists that cinoxacin binds strongly, but reversibly, to DNA, interfering with synthesis of RNA and, consequently, with protein synthesis. It appears to also inhibit DNA gyrase. This enzyme is necessary for proper replicated DNA separation. By inhibiting this enzyme, DNA replication and cell division is inhibited.
AbsorptionRapidly absorbed after oral administration. The presence of food delays absorption but does does not affect total absorption.
Volume of distributionNot Available
Protein binding60 to 80%
Metabolism

Hepatic, with approximately 30-40% metabolized to inactive metabolites.

Route of eliminationNot Available
Half lifeThe mean serum half-life is 1.5 hours. Half-life in patients with impaired renal function may exceed 10 hours.
ClearanceNot Available
ToxicityOral, subcutaneous, and intravenous LD50 in the rat is 3610 mg/kg, 1380 mg/kg, and 860 mg/kg, respectively. Oral, subcutaneous, and intravenous LD50 in the mouse is 2330 mg/kg, 900 mg/kg, and 850 mg/kg, respectively.Symptoms following an overdose of cinoxacin may include anorexia, nausea, vomiting, epigastric distress, and diarrhea. The severity of the epigastric distress and the diarrhea are dose related. Headache, dizziness, insomnia, photophobia, tinnitus, and a tingling sensation have been reported in some patients.
Affected organisms
  • Enteric bacteria and other eubacteria
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9902
Blood Brain Barrier + 0.7001
Caco-2 permeable - 0.515
P-glycoprotein substrate Non-substrate 0.5087
P-glycoprotein inhibitor I Non-inhibitor 0.8358
P-glycoprotein inhibitor II Non-inhibitor 0.8382
Renal organic cation transporter Non-inhibitor 0.7213
CYP450 2C9 substrate Non-substrate 0.8137
CYP450 2D6 substrate Non-substrate 0.8119
CYP450 3A4 substrate Non-substrate 0.5503
CYP450 1A2 substrate Non-inhibitor 0.9045
CYP450 2C9 substrate Non-inhibitor 0.9071
CYP450 2D6 substrate Non-inhibitor 0.9231
CYP450 2C19 substrate Non-inhibitor 0.9025
CYP450 3A4 substrate Non-inhibitor 0.8309
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.6
Ames test AMES toxic 0.9106
Carcinogenicity Non-carcinogens 0.8656
Biodegradation Not ready biodegradable 0.8917
Rat acute toxicity 1.8922 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.8812
hERG inhibition (predictor II) Non-inhibitor 0.9074
Pharmacoeconomics
Manufacturers
  • Eli lilly and co
  • Teva pharmaceuticals usa inc
PackagersNot Available
Dosage forms
FormRouteStrength
CapsuleOral
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point261-262White, W.A.; U.S. Patent 3,669,965; June 13, 1972; assigned to Eli Lilly & Company.
logP1.5Not Available
Predicted Properties
PropertyValueSource
water solubility9.61e-01 g/lALOGPS
logP1.25ALOGPS
logP1.72ChemAxon
logS-2.4ALOGPS
pKa (strongest acidic)4.93ChemAxon
pKa (strongest basic)-4.6ChemAxon
physiological charge-1ChemAxon
hydrogen acceptor count7ChemAxon
hydrogen donor count1ChemAxon
polar surface area88.43ChemAxon
rotatable bond count2ChemAxon
refractivity73.6ChemAxon
polarizability24.72ChemAxon
number of rings3ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

White, W.A.; U.S. Patent 3,669,965; June 13, 1972; assigned to Eli Lilly & Company.

US3669965
General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD00872
KEGG CompoundC08052
PubChem Compound2762
PubChem Substance46507547
ChemSpider2660
ChEBI3716
ChEMBLCHEMBL1208
Therapeutic Targets DatabaseDAP000999
PharmGKBPA449007
RxListhttp://www.rxlist.com/cgi/generic3/cinobac.htm
Drugs.comhttp://www.drugs.com/cons/cinoxacin.html
WikipediaCinoxacin
ATC CodesJ01MB06
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelshow(37.2 KB)
MSDSshow(53.7 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. DNA gyrase subunit A

Kind: protein

Organism: Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
DNA gyrase subunit A P43700 Details

References:

  1. Jariyawat S, Sekine T, Takeda M, Apiwattanakul N, Kanai Y, Sophasan S, Endou H: The interaction and transport of beta-lactam antibiotics with the cloned rat renal organic anion transporter 1. J Pharmacol Exp Ther. 1999 Aug;290(2):672-7. Pubmed
  2. Drlica K, Zhao X: DNA gyrase, topoisomerase IV, and the 4-quinolones. Microbiol Mol Biol Rev. 1997 Sep;61(3):377-92. Pubmed
  3. Neugebauer U, Szeghalmi A, Schmitt M, Kiefer W, Popp J, Holzgrabe U: Vibrational spectroscopic characterization of fluoroquinolones. Spectrochim Acta A Mol Biomol Spectrosc. 2005 May;61(7):1505-17. Pubmed
  4. Tuma J, Connors WH, Stitelman DH, Richert C: On the effect of covalently appended quinolones on termini of DNA duplexes. J Am Chem Soc. 2002 Apr 24;124(16):4236-46. Pubmed

2. DNA

Kind: nucleotide

Organism: Human

Pharmacological action: unknown

Actions: intercalation

Components

Name UniProt ID Details

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
  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
  3. Tuma J, Connors WH, Stitelman DH, Richert C: On the effect of covalently appended quinolones on termini of DNA duplexes. J Am Chem Soc. 2002 Apr 24;124(16):4236-46. Pubmed

Transporters

1. Solute carrier family 22 member 6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 6 Q4U2R8 Details

References:

  1. Jariyawat S, Sekine T, Takeda M, Apiwattanakul N, Kanai Y, Sophasan S, Endou H: The interaction and transport of beta-lactam antibiotics with the cloned rat renal organic anion transporter 1. J Pharmacol Exp Ther. 1999 Aug;290(2):672-7. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on April 04, 2014 13:50