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Identification
NameTemafloxacin
Accession NumberDB01405
TypeSmall Molecule
GroupsWithdrawn
Description

Temafloxacin is a fluoroquinolone antibiotic drug which was withdrawn from sale in the U.S. shortly after its approval in 1992 because of serious adverse reactions resulting in three deaths. [Wikipedia]

Structure
Thumb
Synonyms
Temafloxacina
Temafloxacine
Temafloxacinum
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
OmnifloxNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Temafloxacin hydrochloride
Thumb
  • InChI Key: QKDHBVNJCZBTMR-UHFFFAOYNA-N
  • Monoisotopic Mass: 417.130026072
  • Average Mass: 417.3811
DBSALT000794
Categories
UNII1WZ12GTT67
CAS number108319-06-8
WeightAverage: 417.3811
Monoisotopic: 417.130026072
Chemical FormulaC21H18F3N3O3
InChI KeyInChIKey=QKDHBVNJCZBTMR-UHFFFAOYSA-N
InChI
InChI=1S/C21H18F3N3O3/c1-11-9-26(5-4-25-11)19-8-18-13(7-16(19)24)20(28)14(21(29)30)10-27(18)17-3-2-12(22)6-15(17)23/h2-3,6-8,10-11,25H,4-5,9H2,1H3,(H,29,30)
IUPAC Name
1-(2,4-difluorophenyl)-6-fluoro-7-(3-methylpiperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
SMILES
CC1CN(CCN1)C1=C(F)C=C2C(=O)C(=CN(C2=C1)C1=C(F)C=C(F)C=C1)C(O)=O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as phenylquinolines. These are heterocyclic compounds containing a quinoline moiety substituted with a phenyl group.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassQuinolines and derivatives
Sub ClassPhenylquinolines
Direct ParentPhenylquinolines
Alternative Parents
Substituents
  • Phenylquinoline
  • Quinoline-3-carboxylic acid
  • N-arylpiperazine
  • Fluoroquinolone
  • Dihydroquinolone
  • Aminoquinoline
  • Dihydroquinoline
  • Pyridine carboxylic acid or derivatives
  • Pyridine carboxylic acid
  • Dialkylarylamine
  • Halobenzene
  • Fluorobenzene
  • Benzenoid
  • Pyridine
  • Piperazine
  • 1,4-diazinane
  • Monocyclic benzene moiety
  • 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 DescriptorsNot Available
Pharmacology
IndicationFor the treatment of lower respiratory tract infections, genital and urinary infections like prostatitis, and skin infections.
PharmacodynamicsTemafloxacin (marketed by Abbott Laboratories as Omniflox), is a fluoroquinolone antibiotic drug which was withdrawn from sale in the U.S. shortly after its approval in 1992 because of serious adverse reactions resulting in three deaths. Flouroquinolones such as lomefloxacin possess excellent activity against gram-negative aerobic bacteria such as E.coli and Neisseria gonorrhoea as well as gram-positive bacteria including S. pneumoniae and Staphylococcus aureus. They also posses effective activity against shigella, salmonella, campylobacter, gonococcal organisms, and multi drug resistant pseudomonas and enterobacter.
Mechanism of actionThe bactericidal action of temafloxacin results from interference with the activity of the bacterial enzymes DNA gyrase and topoisomerase IV, which are needed for the transcription and replication of bacterial DNA. DNA gyrase appears to be the primary quinolone target for gram-negative bacteria. Topoisomerase IV appears to be the preferential target in gram-positive organisms. Interference with these two topoisomerases results in strand breakage of the bacterial chromosome, supercoiling, and resealing. As a result DNA replication and transcription is inhibited.
Related Articles
AbsorptionStudies in healthy volunteers indicate that the average bioavailability of temafloxacin exceeds 90%, with little intersubject variability.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Hepatic.

Route of eliminationNot Available
Half lifeApproximately 8 hours in patients with normal renal function.
ClearanceNot Available
ToxicitySevere adverse reactions, including allergic reactions and hemolytic anemia, developed in about fifty patients during the first four months of its use, leading to three patient deaths
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+0.9914
Blood Brain Barrier-0.9863
Caco-2 permeable-0.7526
P-glycoprotein substrateSubstrate0.8741
P-glycoprotein inhibitor INon-inhibitor0.8985
P-glycoprotein inhibitor IINon-inhibitor0.9081
Renal organic cation transporterNon-inhibitor0.7441
CYP450 2C9 substrateNon-substrate0.8128
CYP450 2D6 substrateNon-substrate0.9072
CYP450 3A4 substrateNon-substrate0.7309
CYP450 1A2 substrateNon-inhibitor0.8664
CYP450 2C9 inhibitorNon-inhibitor0.9304
CYP450 2D6 inhibitorNon-inhibitor0.9413
CYP450 2C19 inhibitorNon-inhibitor0.9048
CYP450 3A4 inhibitorNon-inhibitor0.8858
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6993
Ames testAMES toxic0.9067
CarcinogenicityNon-carcinogens0.8318
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.0973 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8332
hERG inhibition (predictor II)Non-inhibitor0.7289
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
logP-0.20BIOBYTE (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.0144 mg/mLALOGPS
logP0.94ALOGPS
logP1.08ChemAxon
logS-4.5ALOGPS
pKa (Strongest Acidic)5.6ChemAxon
pKa (Strongest Basic)8.76ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area72.88 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity104.53 m3·mol-1ChemAxon
Polarizability39.7 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferencesNot Available
External Links
ATC CodesJ01MA05
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
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. Frank KE, Devasthale PV, Gentry EJ, Ravikumar VT, Keschavarz-Shokri A, Mitscher LA, Nilius A, Shen LL, Shawar R, Baker WR: A simple, inexpensive apparatus for performance of preparative scale solution phase multiple parallel synthesis of drug analogs. II. Biological evaluation of a retrospective library of quinolone antiinfective agents. Comb Chem High Throughput Screen. 1998 Jun;1(2):89-99. [PubMed:10500768 ]
  4. Nakanishi N, Yoshida S, Wakebe H, Inoue M, Yamaguchi T, Mitsuhashi S: Mechanisms of clinical resistance to fluoroquinolones in Staphylococcus aureus. Antimicrob Agents Chemother. 1991 Dec;35(12):2562-7. [PubMed:1667255 ]
  5. Nakanishi N, Yoshida S, Wakebe H, Inoue M, Mitsuhashi S: Mechanisms of clinical resistance to fluoroquinolones in Enterococcus faecalis. Antimicrob Agents Chemother. 1991 Jun;35(6):1053-9. [PubMed:1656852 ]
  6. Appelbaum PC: Mechanisms and frequency of resistance to temafloxacin. Am J Med. 1991 Dec 30;91(6A):27S-30S. [PubMed:1662892 ]
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. Nakanishi N, Yoshida S, Wakebe H, Inoue M, Yamaguchi T, Mitsuhashi S: Mechanisms of clinical resistance to fluoroquinolones in Staphylococcus aureus. Antimicrob Agents Chemother. 1991 Dec;35(12):2562-7. [PubMed:1667255 ]
  4. Nakanishi N, Yoshida S, Wakebe H, Inoue M, Mitsuhashi S: Mechanisms of clinical resistance to fluoroquinolones in Enterococcus faecalis. Antimicrob Agents Chemother. 1991 Jun;35(6):1053-9. [PubMed:1656852 ]
  5. Appelbaum PC: Mechanisms and frequency of resistance to temafloxacin. Am J Med. 1991 Dec 30;91(6A):27S-30S. [PubMed:1662892 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
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 July 13, 2007 14:27 / Updated on September 16, 2013 17:14