209467-52-7

Basic information

• Product Name: Ceftobiprole
• Synonyms: Ceftobiprole;5-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)-
• CAS NO: 209467-52-7
• Molecular Formula: C20H22N8O6S2
• Molecular Weight: 534.576
• Mol File: 209467-52-7.mol
• Article Data: 5

Chemical Properties

• Appearance: /
• Density: 2 g/cm³
• Refractive Index: 1.942
• PKA: 2.46±0.50(Predicted)
• CAS DataBase Reference: Ceftobiprole(CAS DataBase Reference)
• NIST Chemistry Reference: Ceftobiprole(209467-52-7)
• EPA Substance Registry System: Ceftobiprole(209467-52-7)

Safety Data

• Hazardous Substances Data: 209467-52-7(Hazardous Substances Data)

Usage

Uses

Broad spectrum antibiotic.

Antimicrobial activity

The most important property distinguishing it from older cephalosporins is activity against methicillin-resistant staphylococci, a property conferred by a high affinity for penicillinbinding protein 2′ (2a). MICs for methicillin-resistant strains are nevertheless somewhat higher than those seen with fully susceptible strains. A similar situation exists with coagulasenegative staphylococci and with Str. pneumoniae, for which strains with reduced susceptibility to penicillin are less susceptible than fully resistant strains, while remaining within therapeutically achievable levels. Otherwise activity approximates to that of cephalosporins of group 4 . Activity against Ps. aeruginosa is modest and much reduced against ceftazidime-resistant strains.

Acquired resistance

It is hydrolyzed by extended spectrum β-lactamases of enterobacteria , which are therefore resistant. The prospects for the emergence of resistance during extensive clinical use are presently unclear, though increased resistance in Staph. aureus appears to be difficult to induce under laboratory conditions.

Pharmacokinetics

Cmax 500 mg (667 mg prodrug): c. 35 mg/L end infusion intravenous (30-min infusion) Plasma half-life: c. 3 h Volume of distribution: 18.4 L Plasma protein binding: 16% The prodrug is rapidly hydrolyzed in plasma to release the active form together with diacetyl (2,3-butanediol) and CO2. Distribution approximates to the extracellular fluid volume in adults. There is no accumulation on repeat dosing in subjects with normal renal function. It is chiefly excreted in urine by glomerular filtration. A urinary concentration exceeding 1 g/L is achieved within the first 2 h of a 500 mg (active drug equivalent) dose and 80–90% of active drug can be recovered within 24 h.

Clinical Use

Ceftobiprole can be used as Broad spectrum antibiotic and in complicated infections of skin and skin structures.

Side effects

Limited studies have so far revealed no unexpected side effects. Nausea, vomiting and altered taste sensation appear to be the most common.

InChI:InChI=1/C20H22N8O6S2/c21-20-24-14(26-36-20)11(25-34)15(29)23-12-17(31)28-13(19(32)33)9(7-35-18(12)28)5-8-2-4-27(16(8)30)10-1-3-22-6-10/h5,10,12,18,22,34H,1-4,6-7H2,(H,23,29)(H,32,33)(H2,21,24,26)/b8-5+,25-11-/t10-,12-,18-/m1/s1

Upstream product

• 733725-06-9 (6R,7R)-7-[(Z)-2-(5-amino-[1,2,4]thiadiazol-3-yl)-2-trityloxyiminoacetylamino]-8-oxo-3-[(E)-(R)-2-oxo-[1,3']bipyrrolidinyl-3-ylidenemethyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid 
• 252188-71-9 ceftobiprole medocaril sodium 
• 376653-42-8 (1R/S,3'R)-(1'-tert-butyloxycarbonyl-2-oxo-[1,3']bipyrrolidinyl-3-yl)-triphenylphosphonium bromide 
• 1256575-34-4 (6R,7R)-7-amino-3[E-(R)-1'-(5-tert-butyloxycarbonyl)-2-oxo-[1,3']bipyrrolidinyl-3-ylidenemethyl]-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid 

Relevant articles and documents

Peptidoglycan Cross-Linking Preferences of Staphylococcus aureus Penicillin-Binding Proteins Have Implications for Treating MRSA Infections

Methicillin-resistant Staphylococcus aureus (MRSA) infections are a global public health problem. MRSA strains have acquired a non-native penicillin-binding protein called PBP2a that cross-links peptidoglycan when the native S. aureus PBPs are inhibited by β-lactams. It has been proposed that the native S. aureus PBPs can use cell wall precursors having different glycine branch lengths (penta-, tri-, or monoglycine), while PBP2a can only cross-link peptidoglycan strands bearing a complete pentaglycine branch. This hypothesis has never been tested because the necessary substrates have not been available. Here, we compared the ability of PBP2a and two native S. aureus transpeptidases to cross-link peptidoglycan strands bearing different glycine branches. We show that purified PBP2a can cross-link glycan strands bearing penta- and triglycine, but not monoglycine, and experiments in cells provide support for these findings. Because PBP2a cannot cross-link peptidoglycan containing monoglycine, this study implicates the enzyme (FemA) that extends the monoglycine branch to triglycine on Lipid II as an ideal target for small molecules that restore sensitivity of MRSA to β-lactams.

METHOD FOR THE PRODUCTION OF CEFTOBIPROLE MEDOCARIL

The present invention relates to a method for the production of organic compounds, in particular sodium (6R,7R)-7-[(Z)-2-(5-amino-[1,2,4]thiadiazol-3-yl)-2-hydroxyimino-acetylamino]-8-oxo-3-[(E)-(R)-1′-(5-methyl-2-oxo-[1,3]-dioxol-4-ylmethoxycarbonyl)-2-o

Vinyl-pyrrolidinone cephalosporins

The present invention relates to compounds having the formula STR1 wherein X, R1, R2, R3, R4, R5, R6, and R7 are as defined herein as well as readily hydrolyzable esters thereof, pharmaceutically acceptable salts of said compounds and hydrates of the compounds of formula I and of their esters and salts. These compounds have valuable pharmacological activity for the treatment and prophylaxis of infectious diseases, especially those caused by methicillin resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa.