(6R,7R)-7-[[(2Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-oxidoiminoacetyl]amino]-8-oxo-3-[(E)-[2-oxo-1-[(3R)-pyrrolidin-1-ium-3-yl]pyrrolidin-3-ylidene]methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
Grundinformationen
- CAS
209467-52-7- Standard-SMILES
Nc1nc(/C(=N/[O-])C(=O)N[C@@H]2C(=O)N3C(C(=O)O)=C(/C=C4\CCN([C@@H]5CC[NH2+]C5)C4=O)CS[C@H]23)ns1- InChIKey
VOAZJEPQLGBXGO-SDAWRPRTSA-N- Summenformel
- C20H22N8O6S2
- Durchschnittliche Molmasse
- 534,6 g/mol
- Monoisotopische Masse
- 534,1103728
Überblick
Ceftobiprole is a fifth-generation semisynthetic cephalosporin antibacterial which is available commercially as the prodrug [ceftobiprole medocaril]. Ceftobiprole is a broad-spectrum agent with demonstrated activity against both Gram-positive and Gram-negative bacteria, including antibiotic-resistant strains of Staphylcoccus aureus (methicillin-resistant Staphylococcus aureus; MRSA). The EMA's Committee for Medicinal Products for Human Use (CHMP) adopted a negative opinion of ceftobiprole medocaril in February 2010, recommending the refusal of its marketing authorization in the European Union primarily due to data quality issues in pivotal clinical studies. It received its first approval in Canada in October 2017 for use in certain patients with bacterial pneumonia, and was subsequently approved in the United States with additional indications for skin and skin structure infections and bacteremia in April 2024.
Namen und Bezeichner
- Bevorzugter Name
- (6R,7R)-7-[[(2Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-oxidoiminoacetyl]amino]-8-oxo-3-[(E)-[2-oxo-1-[(3R)-pyrrolidin-1-ium-3-yl]pyrrolidin-3-ylidene]methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
- IUPAC
- (6R,7R)-7-[[(2Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-oxidoiminoacetyl]amino]-8-oxo-3-[(E)-[2-oxo-1-[(3R)-pyrrolidin-1-ium-3-yl]pyrrolidin-3-ylidene]methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
- Englischer Name
- Ceftobiprole
- Summenformel
- C20H22N8O6S2
- Molmasse
- 534.57
Namen und Synonyme
CS-734BAL 9141CeftobiproleAbscisic Acid Impurity 4cephalosporin,Ceftobiprole,inhibit,vancomycin,penicillin,staphylococci,Bacterial,pyrrolidinone,pathogens,gram-positive,BAL-9141,VRSA,gram-negative,Inhibitor,MRSA,BAL9141,methicillin(6R,7R)-7-((Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(hydroxyimino)acetamido)-8-oxo-3-((E)-((R)-2-oxo-[1,3'-bipyrrolidin]-3-ylidene)methyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid5-Thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylicacid,7-[[(2Z)-2-(5-aMino-1,2,4-thiadiazol-3-yl)-2-(hydroxyiMino)acetyl]aMino]-8-oxo-3-[(E)-[(3'R)-2-oxo[1,3'-bipyrrolidin]-3-ylidene]Methyl]-,(6R,7R)-
Datenbank-Bezeichner
- CAS
209467-52-7- PubChem CID
- 138319339
Eigenschaften
Berechnete Struktureigenschaften
- XLogP
- -3
- Polarare Oberfläche (TPSA)
- 264 Ų
- H-Brücken-Donoren
- 4
- H-Brücken-Akzeptoren
- 12
- Frei drehbare Bindungen
- 6
- Schwere Atome
- 36
- Formalladung
- 0
- Komplexität
- 1.100
Physikochemische Eigenschaften
- Dichte
- 2 · 2.00±0.1 g/cm3(Predicted)
- storage temp.
- -20 °C,unstable · Store at -20°C,unstable in solution, ready to use.
- Löslichkeit
- 5 mg/mL · DMSO : 5 mg/mL (9.35 mM)
- Aggregatzustand
- Solid
- pka
- 2.46 · 2.46±0.50(Predicted)
- Farbe
- Light yellow to yellow
- InChIKey
- VOAZJEPQLGBXGO-SDAWRPRTSA-N
- SMILES
- N12[C@@]([H])([C@H](NC(/C(/C3N=C(N)SN=3)=N\O)=O)C1=O)SCC(/C=C1\CCN([C@@H]3CCNC3)C\1=O)=C2C(O)=O
Sicherheit und Regulatorisches
Sicherheitsangaben dienen nur zur Orientierung und ersetzen weder das Sicherheitsdatenblatt (SDB) des Lieferanten noch geltende Vorschriften oder eine fachliche Bewertung.
Sicherheitsdaten
- wgk
- WGK 3
- Speicherklasse
- 11 - Combustible Solids
Chemie und Industrie
Pharmakologische Informationen
Protein BindingActive [ceftobiprole] is minimally (16%) bound to plasma proteins.
Pharmacodynamics
Ceftobiprole has demonstrated _in vitro_ activity against Gram-positive and Gram-negative bacteria. In a neutropenic murine thigh infection model, therapeutic efficacy is correlated with the time that the unbound plasma concentration of ceftobiprole exceeds the minimum inhibitory concentration (MIC) of _S. aureus_, _S. pneumoniae_, and _Enterobacterales spp._ It is not active against Gram-negative bacteria producing extended-spectrum beta-lactamases (ESBLs) from the TEM, SHV, or CTX-M families, serine carbapenemases (such as KPC), class B metallo-beta-lactamases, class C (AmpC cephalosporinases) if expressed at high levels, and Ambler class D beta-lactamases including carbapenemases. Ceftobiprole is not indicated for use in patients with ventilator-associated bacterial pneumonia (VABP) - in clinical trials, a statistically significant increase in mortality was seen in patients with VABP treated with ceftobiprole medocaril as compared to comparator-treated patients.
Mechanism of Action
[Ceftobiprole], the active moiety of ceftobiprole medocaril, exhibits its bactericidal activity by inhibition of bacterial cell wall synthesis. This activity is mediated through binding to essential penicillin-binding proteins (PBPs) and inhibiting their transpeptidase activity, which is essential for the synthesis of the peptidoglycan layer of the bacterial cell wall. Ceftobiprole has demonstrated _in vitro_ activity against both Gram-positive and Gram-negative bacteria. In Gram-positive bacteria, including methicillin-resistant _Staphylococcus aureus_ (MRSA), Ceftobiprole binds to PBP2a. Ceftobiprole also binds to PBP2b in _Streptococcus pneumoniae_ (penicillin-intermediate), PBP2x in _S. pneumoniae_ (penicillin resistant), and to PBP5 in _Enterococcus faecalis_.
Biological Half-LifeThe half-life of active [ceftobiprole] following multiple-dose administration is approximately 3.3 hours.
Metabolism/Metabolites
Conversion of prodrug ceftobiprole medocaril to the active moiety ceftobiprole occurs rapidly and is mediated by non-specific plasma esterases. Ceftobiprole itself is minimally metabolized to a microbiologically inactive open-ring metabolite, which accounts for approximately 4% of the parent exposure in subject with a normal renal function.
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