Temafloxacin

Identification

Generic Name
Temafloxacin
DrugBank Accession Number
DB01405
Background

Temafloxacin is an antibiotic agent belonging to the fluoroquinolone drug class. It was first approved for use in the U.S. market in 1992, but was withdrawn shortly due to the reports of serious adverse reactions, such as allergic reactions and hemolyric anemia, resulting in three deaths.

Type
Small Molecule
Groups
Withdrawn
Structure
Thumb
Weight
Average: 417.3811
Monoisotopic: 417.130026072
Chemical Formula
C21H18F3N3O3
Synonyms
  • Temafloxacin
  • Temafloxacina
  • Temafloxacine
  • Temafloxacinum

Pharmacology

Indication

For the treatment of lower respiratory tract infections, genital and urinary infections like prostatitis, and skin infections.

Pharmacology
Accelerate your drug discovery research with the industry’s only fully connected ADMET dataset, ideal for:
Machine Learning
Data Science
Drug Discovery
Accelerate your drug discovery research with our fully connected ADMET dataset
Learn more
Contraindications & Blackbox Warnings
Contraindications
Contraindications & Blackbox Warnings
With our commercial data, access important information on dangerous risks, contraindications, and adverse effects.
Learn more
Our Blackbox Warnings cover Risks, Contraindications, and Adverse Effects
Learn more
Pharmacodynamics

Temafloxacin is a fluoroquinolone antibiotic drug, marketed as Omniflox by Abbot Laboratories, which was withdrawn from the market in 1992 due to fatal adverse effects. 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 action

The 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.

TargetActionsOrganism
ADNA gyrase subunit A
inhibitor
Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)
ADNA topoisomerase 4 subunit A
inhibitor
Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)
Absorption

Studies in healthy volunteers indicate that the average bioavailability of temafloxacin exceeds 90%, with little intersubject variability.

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

Hepatic.

Route of elimination

Not Available

Half-life

Approximately 8 hours in patients with normal renal function.

Clearance

Not Available

Adverse Effects
Medicalerrors
Reduce medical errors
and improve treatment outcomes with our comprehensive & structured data on drug adverse effects.
Learn more
Reduce medical errors & improve treatment outcomes with our adverse effects data
Learn more
Toxicity

Severe allergic reactions and hemolytic anemia were observed during the first few months of use leading to fatalities and the drug's eventual withdrawal from the market.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbametapirThe serum concentration of Temafloxacin can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Temafloxacin can be increased when combined with Abatacept.
AbirateroneThe serum concentration of Temafloxacin can be increased when it is combined with Abiraterone.
AcarboseThe therapeutic efficacy of Acarbose can be increased when used in combination with Temafloxacin.
AcebutololThe risk or severity of QTc prolongation can be increased when Acebutolol is combined with Temafloxacin.
AceclofenacAceclofenac may increase the neuroexcitatory activities of Temafloxacin.
AcemetacinAcemetacin may increase the neuroexcitatory activities of Temafloxacin.
AcenocoumarolThe therapeutic efficacy of Acenocoumarol can be increased when used in combination with Temafloxacin.
AcetaminophenThe metabolism of Temafloxacin can be decreased when combined with Acetaminophen.
AcetohexamideThe therapeutic efficacy of Acetohexamide can be increased when used in combination with Temafloxacin.
Interactions
Improve patient outcomes
Build effective decision support tools with the industry’s most comprehensive drug-drug interaction checker.
Learn more
Food Interactions
Not Available

Products

Products
Comprehensive & structured drug product info
From application numbers to product codes, connect different identifiers through our commercial datasets.
Learn more
Easily connect various identifiers back to our datasets
Learn more
Product Ingredients
IngredientUNIICASInChI Key
Temafloxacin hydrochlorideOC5IGJ7J6I105784-61-0DDVJEYDLTXRYAJ-UHFFFAOYSA-N
International/Other Brands
Omniflox

Categories

ATC Codes
J01MA05 — Temafloxacin
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as phenylquinolines. These are heterocyclic compounds containing a quinoline moiety substituted with a phenyl group.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Quinolines and derivatives
Sub Class
Phenylquinolines
Direct Parent
Phenylquinolines
Alternative Parents
Quinoline carboxylic acids / Fluoroquinolones / N-arylpiperazines / Haloquinolines / Hydroquinolones / Aminoquinolines and derivatives / Hydroquinolines / Pyridinecarboxylic acids / Dialkylarylamines / Fluorobenzenes
show 13 more
Substituents
1,4-diazinane / Amine / Amino acid / Amino acid or derivatives / Aminoquinoline / Aromatic heteropolycyclic compound / Aryl fluoride / Aryl halide / Azacycle / Benzenoid
show 33 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
organofluorine compound, tertiary amino compound, N-arylpiperazine, monocarboxylic acid, secondary amino compound, amino acid, quinolone antibiotic, quinolone (CHEBI:77796)
Affected organisms
  • Enteric bacteria and other eubacteria

Chemical Identifiers

UNII
1WZ12GTT67
CAS number
108319-06-8
InChI Key
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

References

General References
Not Available
KEGG Drug
D02469
PubChem Compound
60021
PubChem Substance
46508032
ChemSpider
54143
RxNav
37771
ChEBI
77796
ChEMBL
CHEMBL277100
Wikipedia
Temafloxacin

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
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 RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Drugtargets
Accelerate your drug discovery research
with our fully connected ADMET & drug target dataset.
Learn more
Accelerate your drug discovery research with our ADMET & drug target dataset
Learn more
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, inc...
Gene Name
gyrA
Uniprot ID
P43700
Uniprot Name
DNA gyrase subunit A
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
Uniprot Name
DNA topoisomerase 4 subunit A
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
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Curator comments
Fluoroquinolone drugs are believed to inhibit CYP1A2 enzyme.
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 un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Fuhr U, Anders EM, Mahr G, Sorgel F, Staib AH: Inhibitory potency of quinolone antibacterial agents against cytochrome P450IA2 activity in vivo and in vitro. Antimicrob Agents Chemother. 1992 May;36(5):942-8. [PubMed:1510417]
  2. Randinitis EJ, Alvey CW, Koup JR, Rausch G, Abel R, Bron NJ, Hounslow NJ, Vassos AB, Sedman AJ: Drug interactions with clinafloxacin. Antimicrob Agents Chemother. 2001 Sep;45(9):2543-52. [PubMed:11502527]
  3. Ciprofloxacin FDA label [File]

Drug created on July 13, 2007 20:27 / Updated on March 04, 2021 11:35