Ceforanide
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
- 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
- 7β-[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).
Target Actions Organism APenicillin-binding protein 2 inhibitorBacteroides 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
Drug Interaction (R)-warfarin The risk or severity of bleeding can be increased when Ceforanide is combined with (R)-warfarin. (S)-Warfarin The risk or severity of bleeding can be increased when Ceforanide is combined with (S)-Warfarin. 4-hydroxycoumarin The risk or severity of bleeding can be increased when Ceforanide is combined with 4-hydroxycoumarin. Abacavir Ceforanide may decrease the excretion rate of Abacavir which could result in a higher serum level. Abciximab The therapeutic efficacy of Abciximab can be decreased when used in combination with Ceforanide. Acarbose Ceforanide may decrease the excretion rate of Acarbose which could result in a higher serum level. Aceclofenac Ceforanide may decrease the excretion rate of Aceclofenac which could result in a higher serum level. Acemetacin The risk or severity of nephrotoxicity can be increased when Ceforanide is combined with Acemetacin. Acenocoumarol The risk or severity of bleeding can be increased when Ceforanide is combined with Acenocoumarol. Acetaminophen Ceforanide may decrease the excretion rate of Acetaminophen which could result in a higher serum level. - Food Interactions
- Not Available
References
- General References
- 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]
- 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]
- Cone LA, Barton SM, Woodard DR: Treatment of scleroma with ceforanide. Arch Otolaryngol Head Neck Surg. 1987 Apr;113(4):374-6. [PubMed:3814386]
- 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
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
Property Value Source logP -3.7 Not Available - Predicted Properties
Property Value Source Water Solubility 0.197 mg/mL ALOGPS logP -1.4 ALOGPS logP -3.2 ChemAxon logS -3.4 ALOGPS pKa (Strongest Acidic) 2.55 ChemAxon pKa (Strongest Basic) 9.14 ChemAxon Physiological Charge -1 ChemAxon Hydrogen Acceptor Count 10 ChemAxon Hydrogen Donor Count 4 ChemAxon Polar Surface Area 193.63 Å2 ChemAxon Rotatable Bond Count 10 ChemAxon Refractivity 139.87 m3·mol-1 ChemAxon Polarizability 49.27 Å3 ChemAxon Number of Rings 4 ChemAxon Bioavailability 1 ChemAxon Rule of Five No ChemAxon Ghose Filter No ChemAxon Veber's Rule No ChemAxon MDDR-like Rule Yes ChemAxon - Predicted ADMET features
Property Value Probability Human Intestinal Absorption + 0.5918 Blood Brain Barrier - 0.9659 Caco-2 permeable - 0.7463 P-glycoprotein substrate Substrate 0.7962 P-glycoprotein inhibitor I Non-inhibitor 0.8318 P-glycoprotein inhibitor II Non-inhibitor 0.9607 Renal organic cation transporter Non-inhibitor 0.7981 CYP450 2C9 substrate Non-substrate 0.8253 CYP450 2D6 substrate Non-substrate 0.8124 CYP450 3A4 substrate Non-substrate 0.5421 CYP450 1A2 substrate Non-inhibitor 0.9045 CYP450 2C9 inhibitor Non-inhibitor 0.907 CYP450 2D6 inhibitor Non-inhibitor 0.9231 CYP450 2C19 inhibitor Non-inhibitor 0.9026 CYP450 3A4 inhibitor Non-inhibitor 0.8308 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.577 Ames test Non AMES toxic 0.6325 Carcinogenicity Non-carcinogens 0.8446 Biodegradation Not ready biodegradable 0.8569 Rat acute toxicity 2.3203 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9112 hERG inhibition (predictor II) Non-inhibitor 0.7227
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS Not Available Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not 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
- Barriere SL, Mills J: Ceforanide: antibacterial activity, pharmacology, and clinical efficacy. Pharmacotherapy. 1982 Nov-Dec;2(6):322-7. [PubMed:6762529]
- 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 February 06, 2019 14:26