Identification

Name
Cefroxadine
Accession Number
DB11367
Type
Small Molecule
Groups
Withdrawn
Description

Cefroxadine is an orally available cephalosporin antibiotic. It is structurally related to cefalexin, and both drugs share a similar spectrum of activity. It was used in Italy but has since been withdrawn.

Structure
Thumb
Synonyms
Not Available
External IDs
CGP 9000 / CGP-9000
International/Other Brands
Cefthan-DS (Novartis) / Oraspor (Novartis)
Categories
UNII
B908C4MV2R
CAS number
51762-05-1
Weight
Average: 365.4
Monoisotopic: 365.104541898
Chemical Formula
C16H19N3O5S
InChI Key
RDMOROXKXONCAL-UEKVPHQBSA-N
InChI
InChI=1S/C16H19N3O5S/c1-24-9-7-25-15-11(14(21)19(15)12(9)16(22)23)18-13(20)10(17)8-5-3-2-4-6-8/h2-3,6,10-11,15H,4-5,7,17H2,1H3,(H,18,20)(H,22,23)/t10-,11-,15-/m1/s1
IUPAC Name
(6R,7R)-7-[(2R)-2-amino-2-(cyclohexa-1,4-dien-1-yl)acetamido]-3-methoxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
SMILES
[H][C@]12SCC(OC)=C(N1C(=O)[C@H]2NC(=O)[C@H](N)C1=CCC=CC1)C(O)=O

Pharmacology

Indication

Was used for the treatment of bacterial infections.

Pharmacodynamics

Cefroxadine is a cephalosporin antibiotic which produces a bactericidal effect on susceptible bacteria [1].

Mechanism of action

Cefrixadine is a cephalosporin antibiotic, a class of β-lactam antibiotics similar to penicillins, which binds to and inhibits penicillin binding proteins (PBPs) [3]. PBPs are responsible for catalyzing the transpeptidase reaction which cross-links the peptide side chains on the sugar residues of a peptidoglycan unit, adding the unit to the peptidoglycan layer. This disrupts the balance between the hydrolysis of peptidoglycan, in order to insert new peptidoglycan units, by murein hydrolase and the attachment of the new units which leads to overall destruction of the peptidoglycan layer. With the loss of its peptidoglycan layer the cell also loses its resistance to the high osmotic pressure inside its membrane and lyses.

TargetActionsOrganism
APenicillin-binding protein 1B
inhibitor
Escherichia coli (strain K12)
Absorption

Oral bioavailability of 90% [2].

Volume of distribution

Volume of distrubution of 15 L [2].

Protein binding

Cefrixadine is 10% bound to human plasma proteins [2].

Metabolism
Not Available
Route of elimination

Primarily eliminated in the urine (80-96%) [2].

Half life

The serum half life is 0.9-1.1 h [2].

Clearance

The total body clearance is 340 mL/min and the renal clearance is 250 mL/min [2].

Toxicity
Not Available
Affected organisms
  • Gram negative and gram positive bacteria
  • Escherichia coli
  • Salmonella typhi
  • Staphylococcus aureus
  • Proteus mirabilis
  • Klebsiella pneumoniae
  • Salmonella paratyphi
  • Salmonella schottmuelleri
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AcenocoumarolCefroxadine may increase the anticoagulant activities of Acenocoumarol.
AcetaminophenCefroxadine may decrease the excretion rate of Acetaminophen which could result in a higher serum level.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Cefroxadine which could result in a higher serum level.
AlprazolamCefroxadine may decrease the excretion rate of Alprazolam which could result in a higher serum level.
AmikacinThe risk or severity of nephrotoxicity can be increased when Amikacin is combined with Cefroxadine.
AmilorideAmiloride may increase the excretion rate of Cefroxadine which could result in a lower serum level and potentially a reduction in efficacy.
AmlodipineCefroxadine may decrease the excretion rate of Amlodipine which could result in a higher serum level.
AmoxicillinCefroxadine may decrease the excretion rate of Amoxicillin which could result in a higher serum level.
AmphetamineCefroxadine may decrease the excretion rate of Amphetamine which could result in a higher serum level.
AmpicillinCefroxadine may decrease the excretion rate of Ampicillin which could result in a higher serum level.
Food Interactions
Not Available

References

Synthesis Reference
  • R. Scartazzini, H. Bickel, DE 2331133; eidem, U.S. Patent 4,073,902 (1974, 1978 both to Ciba-Geigy).
  • Jump up ^ R. B. Woodward and H. Bickel, U.S. Patent 4,147,864 (1979); Chem. Abstr., 91, 74633J (1979).
General References
  1. Yasuda K, Kurashige S, Mitsuhashi S: Cefroxadine (CGP-9000), an orally active cephalosporin. Antimicrob Agents Chemother. 1980 Jul;18(1):105-10. [PubMed:6998373]
  2. Bergan T: Pharmacokinetic properties of the cephalosporins. Drugs. 1987;34 Suppl 2:89-104. [PubMed:3319507]
  3. 53. (2011). In Goodman and Gilman's the pharmacological basis of therapeutics, Pharmacological basis of therapeutics (12th ed.). New York: McGraw-Hill. [ISBN:9780071624428]
External Links
KEGG Drug
D01528
KEGG Compound
C12979
PubChem Compound
5284529
PubChem Substance
347827975
ChemSpider
4447587
ChEBI
31379
ChEMBL
CHEMBL3186538
Wikipedia
Cefroxadine
ATC Codes
J01DB11 — Cefroxadine

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.987 mg/mLALOGPS
logP0.65ALOGPS
logP-3.4ChemAxon
logS-2.6ALOGPS
pKa (Strongest Acidic)3.28ChemAxon
pKa (Strongest Basic)7.6ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area121.96 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity94.51 m3·mol-1ChemAxon
Polarizability36.5 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

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

Taxonomy

Description
This compound belongs to the class of organic compounds known as cephalosporins. These are compounds containing a 1,2-thiazine fused to a 2-azetidinone to for a oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid moiety or a derivative thereof.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Lactams
Sub Class
Beta lactams
Direct Parent
Cephalosporins
Alternative Parents
N-acyl-alpha amino acids and derivatives / Alpha amino acid amides / 1,3-thiazines / Vinylogous esters / Tertiary carboxylic acid amides / Secondary carboxylic acid amides / Amino acids / Azetidines / Thiohemiaminal derivatives / Monocarboxylic acids and derivatives
show 8 more
Substituents
Cephalosporin / N-acyl-alpha amino acid or derivatives / Alpha-amino acid amide / Alpha-amino acid or derivatives / Meta-thiazine / Vinylogous ester / Tertiary carboxylic acid amide / Amino acid or derivatives / Amino acid / Azetidine
show 21 more
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
cephalosporin (CHEBI:31379)

Targets

Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Serine-type d-ala-d-ala carboxypeptidase activity
Specific Function
Cell wall formation. Synthesis of cross-linked peptidoglycan from the lipid intermediates. The enzyme has a penicillin-insensitive transglycosylase N-terminal domain (formation of linear glycan str...
Gene Name
mrcB
Uniprot ID
P02919
Uniprot Name
Penicillin-binding protein 1B
Molecular Weight
94291.875 Da
References
  1. Yasuda K, Kurashige S, Mitsuhashi S: Cefroxadine (CGP-9000), an orally active cephalosporin. Antimicrob Agents Chemother. 1980 Jul;18(1):105-10. [PubMed:6998373]

Enzymes

Kind
Protein
Organism
Staphylococcus aureus
Pharmacological action
No
Actions
Substrate
General Function
Beta-lactamase activity
Specific Function
Not Available
Gene Name
blaZ
Uniprot ID
P00807
Uniprot Name
Beta-lactamase
Molecular Weight
31348.98 Da
References
  1. Yasuda K, Kurashige S, Mitsuhashi S: Cefroxadine (CGP-9000), an orally active cephalosporin. Antimicrob Agents Chemother. 1980 Jul;18(1):105-10. [PubMed:6998373]

Drug created on February 10, 2016 15:35 / Updated on August 02, 2018 06:23