Identification

Name
Cefradine
Accession Number
DB01333
Type
Small Molecule
Groups
Approved
Description

A semi-synthetic cephalosporin antibiotic. [PubChem]

Structure
Thumb
Synonyms
  • (6R,7R)-7-((R)-2-Amino-2-(1,4-cyclohexadien-1-yl)acetamido)-3-methyl-8-oxo-5-thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acid
  • (6R,7R)-7-{[(2R)-2-amino-2-cyclohexa-1,4-dien-1-ylacetyl]amino}-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
  • 7-(D-2-Amino-2-(1,4-cyclohexadienyl)acetamide)desacetoxycephalosporanicacid
  • Anspor
  • CED
  • Cefradina
  • Cefradine
  • Cefradinum
  • Cephradin
  • Cephradine
  • Eskacef
  • Sefril
International/Other Brands
Intracef (Beximco Pharma) / Lebac (Square pharmaceuticals Ltd.) / Reocef (Rephco Pharmaceuticals Ltd.) / Sefril (ACME laboratories Ltd.) / Velosef
Categories
UNII
9YA6SX5S4D
CAS number
38821-53-3
Weight
Average: 349.405
Monoisotopic: 349.109626801
Chemical Formula
C16H19N3O4S
InChI Key
RDLPVSKMFDYCOR-UEKVPHQBSA-N
InChI
InChI=1S/C16H19N3O4S/c1-8-7-24-15-11(14(21)19(15)12(8)16(22)23)18-13(20)10(17)9-5-3-2-4-6-9/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-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
SMILES
[H][[email protected]]12SCC(C)=C(N1C(=O)[[email protected]]2NC(=O)[[email protected]](N)C1=CCC=CC1)C(O)=O

Pharmacology

Indication
Not Available
Structured Indications
Not Available
Pharmacodynamics
Not Available
Mechanism of action

Cefradine is a first generation cephalosporin antibiotic with a spectrum of activity similar to Cefalexin. Cefradine, like the penicillins, is a beta-lactam antibiotic. By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, it inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that Cefradine interferes with an autolysin inhibitor.

TargetActionsOrganism
APenicillin-binding protein 1A
inhibitor
Escherichia coli (strain K12)
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination

Over 90 percent of the drug is excreted unchanged in the urine within six hours.

Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcenocoumarolCefradine may increase the anticoagulant activities of Acenocoumarol.Approved
AripiprazoleThe serum concentration of Aripiprazole can be decreased when it is combined with Cefradine.Approved, Investigational
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Cefradine.Investigational
ClorindioneCefradine may increase the anticoagulant activities of Clorindione.Experimental
DicoumarolCefradine may increase the anticoagulant activities of Dicoumarol.Approved
DiphenadioneCefradine may increase the anticoagulant activities of Diphenadione.Experimental
Ethyl biscoumacetateCefradine may increase the anticoagulant activities of Ethyl biscoumacetate.Withdrawn
FluindioneCefradine may increase the anticoagulant activities of Fluindione.Investigational
PhenindioneCefradine may increase the anticoagulant activities of Phenindione.Approved, Investigational
PhenprocoumonCefradine may increase the anticoagulant activities of Phenprocoumon.Approved, Investigational
Picosulfuric acidThe therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Cefradine.Approved
ProbenecidThe serum concentration of Cefradine can be increased when it is combined with Probenecid.Approved
SaxagliptinThe serum concentration of Saxagliptin can be decreased when it is combined with Cefradine.Approved
TioclomarolCefradine may increase the anticoagulant activities of Tioclomarol.Experimental
WarfarinCefradine may increase the anticoagulant activities of Warfarin.Approved
Food Interactions
Not Available

References

Synthesis Reference

Dennis Heemskerk, Anja Gerarda Hogenboom, Carlos Lenhardt, Harold Moody, Theodorus Johannes Godfried Maria Dooren, "Process for the preparation of cephradine." U.S. Patent US20060189802, issued August 24, 2006.

US20060189802
General References
  1. Neiss ES: Cephradine--a summary of preclinical studies and clinical pharmacology. J Ir Med Assoc. 1973 Mar 24;Suppl:1-12. [PubMed:4572639]
External Links
Human Metabolome Database
HMDB15428
KEGG Drug
D00264
KEGG Compound
C06897
PubChem Compound
38103
PubChem Substance
46505082
ChemSpider
34933
BindingDB
50370585
ChEBI
3547
ChEMBL
CHEMBL1604
Therapeutic Targets Database
DAP000454
PharmGKB
PA448890
Wikipedia
Cefradine
ATC Codes
J01DB09 — Cefradine

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

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

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)140 °CPhysProp
water solubility2.13E+004 mg/LYALKOWSKY,SH & DANNENFELSER,RM (1992)
Predicted Properties
PropertyValueSource
Water Solubility0.778 mg/mLALOGPS
logP0.7ALOGPS
logP-2.4ChemAxon
logS-2.6ALOGPS
pKa (Strongest Acidic)3.46ChemAxon
pKa (Strongest Basic)7.6ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area112.73 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity92 m3·mol-1ChemAxon
Polarizability33.19 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.7238
Blood Brain Barrier-0.9942
Caco-2 permeable-0.8957
P-glycoprotein substrateSubstrate0.7962
P-glycoprotein inhibitor INon-inhibitor0.8781
P-glycoprotein inhibitor IINon-inhibitor0.9946
Renal organic cation transporterNon-inhibitor0.9536
CYP450 2C9 substrateNon-substrate0.8401
CYP450 2D6 substrateNon-substrate0.8278
CYP450 3A4 substrateNon-substrate0.5268
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9254
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8698
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9579
Ames testNon AMES toxic0.6896
CarcinogenicityNon-carcinogens0.9204
BiodegradationNot ready biodegradable0.9857
Rat acute toxicity1.4329 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9973
hERG inhibition (predictor II)Non-inhibitor0.8625
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 GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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 n-acyl-alpha amino acids and derivatives. These are compounds containing an alpha amino acid (or a derivative thereof) which bears an acyl group at its terminal nitrogen atom.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
N-acyl-alpha amino acids and derivatives
Alternative Parents
Cephems / 1,3-thiazines / Tertiary carboxylic acid amides / Amino acids / Azetidines / Thiohemiaminal derivatives / Propargyl-type 1,3-dipolar organic compounds / Monocarboxylic acids and derivatives / Azacyclic compounds / Dialkylthioethers
show 7 more
Substituents
N-acyl-alpha amino acid or derivatives / Cephem / Meta-thiazine / Beta-lactam / Tertiary carboxylic acid amide / Azetidine / Carboxamide group / Amino acid / Lactam / Carboximidic acid
show 22 more
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
cephalosporin (CHEBI:3547)

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
mrcA
Uniprot ID
P02918
Uniprot Name
Penicillin-binding protein 1A
Molecular Weight
93635.545 Da
References
  1. Sharma UK, Dwarakanath P, Banerjee N, Town C, Balganesh TS: Expression and characterization of the ponA (ORF I) gene of Haemophilus influenzae: functional complementation in a heterologous system. J Bacteriol. 1995 Dec;177(23):6745-50. [PubMed:7592463]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Vitamin d3 25-hydroxylase activity
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 performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Yasuda K, Ranade A, Venkataramanan R, Strom S, Chupka J, Ekins S, Schuetz E, Bachmann K: A comprehensive in vitro and in silico analysis of antibiotics that activate pregnane X receptor and induce CYP3A4 in liver and intestine. Drug Metab Dispos. 2008 Aug;36(8):1689-97. doi: 10.1124/dmd.108.020701. Epub 2008 May 27. [PubMed:18505790]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Symporter activity
Specific Function
Sodium-ion dependent, high affinity carnitine transporter. Involved in the active cellular uptake of carnitine. Transports one sodium ion with one molecule of carnitine. Also transports organic cat...
Gene Name
SLC22A5
Uniprot ID
O76082
Uniprot Name
Solute carrier family 22 member 5
Molecular Weight
62751.08 Da
References
  1. Ganapathy ME, Huang W, Rajan DP, Carter AL, Sugawara M, Iseki K, Leibach FH, Ganapathy V: beta-lactam antibiotics as substrates for OCTN2, an organic cation/carnitine transporter. J Biol Chem. 2000 Jan 21;275(3):1699-707. [PubMed:10636865]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Proton-dependent oligopeptide secondary active transmembrane transporter activity
Specific Function
Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides. May constitute a major route for the absorption of protein digestion end-products.
Gene Name
SLC15A1
Uniprot ID
P46059
Uniprot Name
Solute carrier family 15 member 1
Molecular Weight
78805.265 Da
References
  1. Han H, de Vrueh RL, Rhie JK, Covitz KM, Smith PL, Lee CP, Oh DM, Sadee W, Amidon GL: 5'-Amino acid esters of antiviral nucleosides, acyclovir, and AZT are absorbed by the intestinal PEPT1 peptide transporter. Pharm Res. 1998 Aug;15(8):1154-9. [PubMed:9706043]
  2. Han HK, Rhie JK, Oh DM, Saito G, Hsu CP, Stewart BH, Amidon GL: CHO/hPEPT1 cells overexpressing the human peptide transporter (hPEPT1) as an alternative in vitro model for peptidomimetic drugs. J Pharm Sci. 1999 Mar;88(3):347-50. [PubMed:10052994]
  3. Saito H, Okuda M, Terada T, Sasaki S, Inui K: Cloning and characterization of a rat H+/peptide cotransporter mediating absorption of beta-lactam antibiotics in the intestine and kidney. J Pharmacol Exp Ther. 1995 Dec;275(3):1631-7. [PubMed:8531138]
  4. Terada T, Saito H, Mukai M, Inui K: Recognition of beta-lactam antibiotics by rat peptide transporters, PEPT1 and PEPT2, in LLC-PK1 cells. Am J Physiol. 1997 Nov;273(5 Pt 2):F706-11. [PubMed:9374833]
  5. Terada T, Saito H, Mukai M, Inui K: Characterization of stably transfected kidney epithelial cell line expressing rat H+/peptide cotransporter PEPT1: localization of PEPT1 and transport of beta-lactam antibiotics. J Pharmacol Exp Ther. 1997 Jun;281(3):1415-21. [PubMed:9190878]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Peptide:proton symporter activity
Specific Function
Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides.
Gene Name
SLC15A2
Uniprot ID
Q16348
Uniprot Name
Solute carrier family 15 member 2
Molecular Weight
81782.77 Da
References
  1. Terada T, Saito H, Mukai M, Inui K: Recognition of beta-lactam antibiotics by rat peptide transporters, PEPT1 and PEPT2, in LLC-PK1 cells. Am J Physiol. 1997 Nov;273(5 Pt 2):F706-11. [PubMed:9374833]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one ...
Gene Name
SLC22A6
Uniprot ID
Q4U2R8
Uniprot Name
Solute carrier family 22 member 6
Molecular Weight
61815.78 Da
References
  1. Cihlar T, Ho ES: Fluorescence-based assay for the interaction of small molecules with the human renal organic anion transporter 1. Anal Biochem. 2000 Jul 15;283(1):49-55. [PubMed:10929807]

Drug created on June 30, 2007 12:05 / Updated on November 09, 2017 02:58