Identification

Name
Ceforanide
Accession Number
DB00923  (APRD00853)
Type
Small Molecule
Groups
Approved
Description

Ceforanide is a second-generation parenteral cephalosporin antibiotic. It has a longer elimination half-life than any currently available cephalosporin. Its activity is very similar to that of cefamandole, a second-generation cephalosporin, except that ceforanide is less active against most gram-positive organisms. Many coliforms, including Escherichia coli, Klebsiella, Enterobacter, and Proteus, are susceptible to ceforanide, as are most strains of Salmonella, Shigella, Hemophilus, Citrobacter and Arizona species.

Structure
Thumb
Synonyms
  • (6R,7R)-7-[[2-[2-(Aminomethyl)phenyl]acetyl]amino]-3-[[1-(carboxymethyl)tetrazol-5-yl]sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
  • 7-[O-(Aminomethyl)phenylacetamido]-3-[[[1-(carboxymethyl)-1H-tetrazol-5-yl]thio]methyl]-3-cephem-4-carboxylic acid
  • 7beta-[2-(Aminomethyl)phenyl]acetamido-3-{[1-(carboxymethyl)-1H-tetrazol-5-yl]sulfanyl}methyl-3,4-didehydrocepham-4-carboxylic acid
  • Ceforanide
  • Ceforanido
  • Ceforanidum
External IDs
BL-S786
International/Other Brands
Precef
Categories
UNII
8M1YF8951V
CAS number
60925-61-3
Weight
Average: 519.554
Monoisotopic: 519.099472819
Chemical Formula
C20H21N7O6S2
InChI Key
SLAYUXIURFNXPG-CRAIPNDOSA-N
InChI
InChI=1S/C20H21N7O6S2/c21-6-11-4-2-1-3-10(11)5-13(28)22-15-17(31)27-16(19(32)33)12(8-34-18(15)27)9-35-20-23-24-25-26(20)7-14(29)30/h1-4,15,18H,5-9,21H2,(H,22,28)(H,29,30)(H,32,33)/t15-,18-/m1/s1
IUPAC Name
(6R,7R)-7-{2-[2-(aminomethyl)phenyl]acetamido}-3-({[1-(carboxymethyl)-1H-1,2,3,4-tetrazol-5-yl]sulfanyl}methyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
SMILES
[H][C@]12SCC(CSC3=NN=NN3CC(O)=O)=C(N1C(=O)[C@H]2NC(=O)CC1=CC=CC=C1CN)C(O)=O

Pharmacology

Indication

For the treatment of infections caused by susceptible organisms.

Pharmacodynamics

Ceforanide is a semisynthetic second-generation cephalosporin. The cephalosporins are bactericidal drugs with both gram-positive and gram-negative activity. They inhibit bacterial cell wall synthesis in a way similar to the penicillins.

Mechanism of action

The bactericidal activity of ceforanide results from the inhibition of cell wall synthesis via affinity for penicillin-binding proteins (PBPs).

TargetActionsOrganism
APenicillin-binding protein 2
inhibitor
Bacteroides fragilis
Absorption

Rapidly absorbed following intramuscular injection.

Volume of distribution
Not Available
Protein binding

80.6%

Metabolism

The major drug elimination route was urinary excretion with 85% of the dose being excreted unchanged in the urine within 12 hr, and no metabolites with antibiotic activity were observed in urine.

Route of elimination
Not Available
Half life

2.6 to 2.98 hours

Clearance
Not Available
Toxicity

Adverse effects following overdosage include nausea, vomiting, epigastric distress, diarrhea, and convulsions.

Affected organisms
  • Enteric bacteria and other eubacteria
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of bleeding can be increased when Ceforanide is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of bleeding can be increased when Ceforanide is combined with (S)-Warfarin.
4-hydroxycoumarinThe risk or severity of bleeding can be increased when Ceforanide is combined with 4-hydroxycoumarin.
AbacavirCeforanide may decrease the excretion rate of Abacavir which could result in a higher serum level.
AcarboseCeforanide may decrease the excretion rate of Acarbose which could result in a higher serum level.
AceclofenacCeforanide may decrease the excretion rate of Aceclofenac which could result in a higher serum level.
AcemetacinThe risk or severity of nephrotoxicity can be increased when Ceforanide is combined with Acemetacin.
AcenocoumarolThe risk or severity of bleeding can be increased when Ceforanide is combined with Acenocoumarol.
AcetaminophenCeforanide may decrease the excretion rate of Acetaminophen which could result in a higher serum level.
Acetylsalicylic acidThe risk or severity of nephrotoxicity can be increased when Ceforanide is combined with Acetylsalicylic acid.
Food Interactions
Not Available

References

General References
  1. Crowle AJ, Sbarbaro JA, May MH: Effects of isoniazid and of ceforanide against virulent tubercle bacilli in cultured human macrophages. Tubercle. 1988 Mar;69(1):15-25. [PubMed:3140456]
  2. Campoli-Richards DM, Lackner TE, Monk JP: Ceforanide. A review of its antibacterial activity, pharmacokinetic properties and clinical efficacy. Drugs. 1987 Oct;34(4):411-37. [PubMed:3315624]
  3. Cone LA, Barton SM, Woodard DR: Treatment of scleroma with ceforanide. Arch Otolaryngol Head Neck Surg. 1987 Apr;113(4):374-6. [PubMed:3814386]
  4. Barriere SL, Mills J: Ceforanide: antibacterial activity, pharmacology, and clinical efficacy. Pharmacotherapy. 1982 Nov-Dec;2(6):322-7. [PubMed:6762529]
External Links
Human Metabolome Database
HMDB0015059
KEGG Drug
D00259
KEGG Compound
C06884
PubChem Compound
43507
PubChem Substance
46504532
ChemSpider
39656
ChEBI
3495
ChEMBL
CHEMBL1201046
Therapeutic Targets Database
DAP001175
PharmGKB
PA164746057
Wikipedia
Ceforanide
ATC Codes
J01DC11 — Ceforanide

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
  • Apothecon inc div bristol myers squibb
  • Bristol laboratories inc div bristol myers co
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP-3.7Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.197 mg/mLALOGPS
logP-1.4ALOGPS
logP-3.2ChemAxon
logS-3.4ALOGPS
pKa (Strongest Acidic)2.55ChemAxon
pKa (Strongest Basic)9.14ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count10ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area193.63 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity139.87 m3·mol-1ChemAxon
Polarizability49.27 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.5918
Blood Brain Barrier-0.9659
Caco-2 permeable-0.7463
P-glycoprotein substrateSubstrate0.7962
P-glycoprotein inhibitor INon-inhibitor0.8318
P-glycoprotein inhibitor IINon-inhibitor0.9607
Renal organic cation transporterNon-inhibitor0.7981
CYP450 2C9 substrateNon-substrate0.8253
CYP450 2D6 substrateNon-substrate0.8124
CYP450 3A4 substrateNon-substrate0.5421
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.8308
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.577
Ames testNon AMES toxic0.6325
CarcinogenicityNon-carcinogens0.8446
BiodegradationNot ready biodegradable0.8569
Rat acute toxicity2.3203 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9112
hERG inhibition (predictor II)Non-inhibitor0.7227
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 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 / Phenylacetamides / Benzylamines / Phenylmethylamines / Alkylarylthioethers / Aralkylamines / 1,3-thiazines / Dicarboxylic acids and derivatives / Tertiary carboxylic acid amides / Tetrazoles
show 14 more
Substituents
Cephalosporin / N-acyl-alpha amino acid or derivatives / Alpha-amino acid or derivatives / Phenylacetamide / Phenylmethylamine / Aryl thioether / Benzylamine / Alkylarylthioether / Aralkylamine / Meta-thiazine
show 32 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
cephalosporin (CHEBI:3495)

Targets

Kind
Protein
Organism
Bacteroides fragilis
Pharmacological action
Yes
Actions
Inhibitor
General Function
Penicillin binding
Specific Function
Not Available
Gene Name
pbpA
Uniprot ID
Q70KI2
Uniprot Name
Penicillin-binding protein 2
Molecular Weight
69434.305 Da
References
  1. Barriere SL, Mills J: Ceforanide: antibacterial activity, pharmacology, and clinical efficacy. Pharmacotherapy. 1982 Nov-Dec;2(6):322-7. [PubMed:6762529]
  2. Yotsuji A, Mitsuyama J, Hori R, Yasuda T, Saikawa I, Inoue M, Mitsuhashi S: Mechanism of action of cephalosporins and resistance caused by decreased affinity for penicillin-binding proteins in Bacteroides fragilis. Antimicrob Agents Chemother. 1988 Dec;32(12):1848-53. [PubMed:3266730]

Drug created on June 13, 2005 07:24 / Updated on November 02, 2018 04:52