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Identification
NameCefacetrile
Accession NumberDB01414
Typesmall molecule
Groupsapproved
Description

A derivative of 7-aminocephalosporanic acid.

Structure
Thumb
Synonyms
SynonymLanguageCode
CefacetriloSpanishINN
CefacetrilumLatinINN
CephacetrileNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
CelosporCiba
CeltolTakeda
Brand mixturesNot Available
Categories
CAS number10206-21-0
WeightAverage: 339.324
Monoisotopic: 339.052505853
Chemical FormulaC13H13N3O6S
InChI KeyInChIKey=RRYMAQUWDLIUPV-BXKDBHETSA-N
InChI
InChI=1S/C13H13N3O6S/c1-6(17)22-4-7-5-23-12-9(15-8(18)2-3-14)11(19)16(12)10(7)13(20)21/h9,12H,2,4-5H2,1H3,(H,15,18)(H,20,21)/t9-,12-/m1/s1
IUPAC Name
(6R,7R)-3-[(acetyloxy)methyl]-7-(2-cyanoacetamido)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
SMILES
[H][C@]12SCC(COC(C)=O)=C(N1C(=O)[C@H]2NC(=O)CC#N)C(O)=O
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassLactams
SubclassBeta Lactams
Direct parentCephalosporins
Alternative parentsN-acyl-alpha Amino Acids and Derivatives; 1,3-Thiazines; Tertiary Carboxylic Acid Amides; Hemiaminals; Azetidines; Carboxylic Acid Esters; Tertiary Amines; Secondary Carboxylic Acid Amides; Enolates; Ethers; Enamines; Carboxylic Acids; Nitriles; Polyamines; Aminals; Thioethers
Substituentsn-acyl-alpha amino acid or derivative; meta-thiazine; tertiary carboxylic acid amide; hemiaminal; azetidine; carboxylic acid ester; tertiary amine; secondary carboxylic acid amide; carboxamide group; nitrile; carbonitrile; polyamine; thioether; ether; enamine; enolate; aminal; carboxylic acid derivative; carboxylic acid; amine; organonitrogen compound
Classification descriptionThis compound belongs to the 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 moeity or a derivative thereof.
Pharmacology
IndicationCefacetrile is a broad-spectrum first generation cephalosporin antibiotic effective in Gram-positive and Gram-negative bacterial infections.
PharmacodynamicsCefacetrile is effective against many Gram-positive bacterial strains and somewhat less effective against Gram-negative species. It works by inhibition of bacterial cell wall synthesis. It attains high serum levels and is excreted quickly via the urine.
Mechanism of actionIn vitro tests demonstrate that the bactericidal action of cephalosporins results from inhibition of cell wall synthesis. 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.
AbsorptionNot Available
Volume of distribution

Vd of 0.2 to 0.5L/.kg

Protein binding23 to 38%
Metabolism
Route of eliminationNot Available
Half life1.2 hours
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Enteric bacteria and other eubacteria
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption - 0.9435
Blood Brain Barrier - 0.9965
Caco-2 permeable - 0.754
P-glycoprotein substrate Substrate 0.7774
P-glycoprotein inhibitor I Non-inhibitor 0.7686
P-glycoprotein inhibitor II Non-inhibitor 0.9626
Renal organic cation transporter Non-inhibitor 0.9013
CYP450 2C9 substrate Non-substrate 0.7919
CYP450 2D6 substrate Non-substrate 0.823
CYP450 3A4 substrate Non-substrate 0.5
CYP450 1A2 substrate Non-inhibitor 0.8122
CYP450 2C9 substrate Non-inhibitor 0.8282
CYP450 2D6 substrate Non-inhibitor 0.9145
CYP450 2C19 substrate Non-inhibitor 0.8132
CYP450 3A4 substrate Non-inhibitor 0.9152
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8735
Ames test Non AMES toxic 0.6895
Carcinogenicity Non-carcinogens 0.9237
Biodegradation Not ready biodegradable 0.9705
Rat acute toxicity 1.8811 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9933
hERG inhibition (predictor II) Non-inhibitor 0.9062
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point168-170Bickel, H., Bosshardt, R., Fechtig, B., Schenker, K. and Urech, J.; U.S. Patent 3,483,197; December 9,1969; assigned to Ciba Corporation.
logP-0.45HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
water solubility2.43e+00 g/lALOGPS
logP-0.52ALOGPS
logP-1.8ChemAxon
logS-2.1ALOGPS
pKa (strongest acidic)3.31ChemAxon
pKa (strongest basic)-6.2ChemAxon
physiological charge-2ChemAxon
hydrogen acceptor count6ChemAxon
hydrogen donor count2ChemAxon
polar surface area136.8ChemAxon
rotatable bond count6ChemAxon
refractivity77.51ChemAxon
polarizability31.32ChemAxon
number of rings2ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Bickel, H., Bosshardt, R., Fechtig, B., Schenker, K. and Urech, J.; U.S. Patent 3,483,197;
December 9,1969; assigned to Ciba Corporation.

General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD07629
PubChem Compound91562
PubChem Substance46504767
ChemSpider82675
Therapeutic Targets DatabaseDAP001172
PharmGKBPA164776752
WikipediaCefacetrile
ATC CodesJ01DB10
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

1. Penicillin-binding protein 1A

Kind: protein

Organism: Escherichia coli (strain K12)

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Penicillin-binding protein 1A P02918 Details

References:

  1. 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
  2. Truesdell SE, Zurenko GE, Laborde AL: Interaction of cephalosporins with penicillin-binding proteins of methicillin-resistant Staphylococcus aureus. J Antimicrob Chemother. 1989 Apr;23 Suppl D:13-9. Pubmed

2. Penicillin-binding protein 1B

Kind: protein

Organism: Escherichia coli (strain K12)

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Penicillin-binding protein 1B P02919 Details

References:

  1. Truesdell SE, Zurenko GE, Laborde AL: Interaction of cephalosporins with penicillin-binding proteins of methicillin-resistant Staphylococcus aureus. J Antimicrob Chemother. 1989 Apr;23 Suppl D:13-9. Pubmed
  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

1. Solute carrier family 22 member 6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 6 Q4U2R8 Details

References:

  1. Takeda M, Babu E, Narikawa S, Endou H: Interaction of human organic anion transporters with various cephalosporin antibiotics. Eur J Pharmacol. 2002 Mar 8;438(3):137-42. Pubmed
  2. Jariyawat S, Sekine T, Takeda M, Apiwattanakul N, Kanai Y, Sophasan S, Endou H: The interaction and transport of beta-lactam antibiotics with the cloned rat renal organic anion transporter 1. J Pharmacol Exp Ther. 1999 Aug;290(2):672-7. Pubmed
  3. Jung KY, Takeda M, Shimoda M, Narikawa S, Tojo A, Kim DK, Chairoungdua A, Choi BK, Kusuhara H, Sugiyama Y, Sekine T, Endou H: Involvement of rat organic anion transporter 3 (rOAT3) in cephaloridine-induced nephrotoxicity: in comparison with rOAT1. Life Sci. 2002 Mar 8;70(16):1861-74. Pubmed
  4. Uwai Y, Saito H, Inui K: Rat renal organic anion transporter rOAT1 mediates transport of urinary-excreted cephalosporins, but not of biliary-excreted cefoperazone. Drug Metab Pharmacokinet. 2002;17(2):125-9. Pubmed

2. Solute carrier family 22 member 8

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 8 Q8TCC7 Details

References:

  1. Takeda M, Babu E, Narikawa S, Endou H: Interaction of human organic anion transporters with various cephalosporin antibiotics. Eur J Pharmacol. 2002 Mar 8;438(3):137-42. Pubmed
  2. Jariyawat S, Sekine T, Takeda M, Apiwattanakul N, Kanai Y, Sophasan S, Endou H: The interaction and transport of beta-lactam antibiotics with the cloned rat renal organic anion transporter 1. J Pharmacol Exp Ther. 1999 Aug;290(2):672-7. Pubmed
  3. Jung KY, Takeda M, Shimoda M, Narikawa S, Tojo A, Kim DK, Chairoungdua A, Choi BK, Kusuhara H, Sugiyama Y, Sekine T, Endou H: Involvement of rat organic anion transporter 3 (rOAT3) in cephaloridine-induced nephrotoxicity: in comparison with rOAT1. Life Sci. 2002 Mar 8;70(16):1861-74. Pubmed
  4. Uwai Y, Saito H, Inui K: Rat renal organic anion transporter rOAT1 mediates transport of urinary-excreted cephalosporins, but not of biliary-excreted cefoperazone. Drug Metab Pharmacokinet. 2002;17(2):125-9. Pubmed

Comments
Drug created on July 23, 2007 06:31 / Updated on April 03, 2014 11:16