Sulopenem Etzadroxil
Grundinformationen
- CAS
1000296-70-7- Standard-SMILES
CCC(CC)C(=O)OCOC(=O)C1=C(S[C@H]2CC[S@@](=O)C2)S[C@@H]2[C@@H]([C@@H](C)O)C(=O)N12- InChIKey
NBPVNGWRLGHULH-CSOWVJSESA-N- Summenformel
- C19H27NO7S3
- Durchschnittliche Molmasse
- 477,6 g/mol
- Monoisotopische Masse
- 477,0949652
Überblick
Sulopenem etzadroxil is a prodrug of the penem antibacterial [sulopenem]. Like other beta-lactam antibacterials, it is a time-dependent inhibitor of bacterial cell wall synthesis. Sulopenem etzadroxil was approved by the FDA in October 2024 for the treatment of uncomplicated urinary tract infections. It is administered in combination with [probenecid] in order to increase antibiotic exposure.
Namen und Bezeichner
- Bevorzugter Name
- Sulopenem Etzadroxil
- IUPAC
- 2-ethylbutanoyloxymethyl (5R,6S)-6-[(1R)-1-hydroxyethyl]-7-oxo-3-[(1R,3S)-1-oxothiolan-3-yl]sulfanyl-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate
- Englischer Name
- Sulopenem etzadroxil
- Summenformel
- C19H27NO7S3
- Molmasse
- 477.62
Namen und Synonyme
SULOPENEM ETZADROXIL1000296-70-7Sulopenem etzadroxil (USAN)Sulopenem etzadroxil [USAN]492M3I304TPF-037092704-Thia-1-azabicyclo(3.2.0)hept-2-ene-2-carboxylic acid, 6-((1R)-1-hydroxyethyl)-7-oxo-3-(((1R,3S)-tetrahydro-1-oxido-3-thienyl)thio)-, (2-ethyl-1-oxobutoxy)methyl ester, (5R,6S)-METHYLENE 2-ETHYLBUTANOATE (5R,6S)-6-((1R)-1-HYDROXYETHYL)-7-OXO-3-(((1R,3S)-1-OXOTETRAHYDRO-1H-1.LAMBA.(SUP 4)-THIOPHEN-3-YL)SULFANYL)-4-THIA-1-AZABICYCLO(3.2.0)HEPT-2-ENE-2-CARBOXYLATEPF03709270UNII-492M3I304TRefChem:186740Methylene 2-Ethylbutanoate (5R,6S)-6-((1R)-1-Hydroxyethyl)-7-Oxo-3-(((1R,3S)-1-Oxotetrahydro-1H-1-lambda(Sup 4)-Thiophen-3-yl)Sulfanyl)-4-Thia-1-Azabicyclo(3.2.0)Hept-2-Ene-2-Carboxylate
Weitere Namen anzeigen
11. Suropenolulopenem etzadroxilSulopenem etzadroxil (PF-03709270)PF 03709270 (Synonyms: ulopenem etzadroxil)Sulopenem Etzadroxil,1000296-70-7,Pharmaceutical Chemicals((2-ethylbutanoyl)oxy)methyl (5R,6S)-6-((R)-1-hydroxyethyl)-3-(((1R,3S)-1-oxidotetrahydrothiophen-3-yl)thio)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate
Eigenschaften
Berechnete Struktureigenschaften
- XLogP
- 2,1
- Polarare Oberfläche (TPSA)
- 180 Ų
- H-Brücken-Donoren
- 1
- H-Brücken-Akzeptoren
- 10
- Frei drehbare Bindungen
- 11
- Schwere Atome
- 30
- Formalladung
- 0
- Komplexität
- 767
Experimentelle und physikochemische Eigenschaften
Human Drugs
FDA approved drugs -> Active ingredient
FDA approved drugs -> Active ingredient
Physikochemische Eigenschaften
- Siedepunkt
- 722.993 · 722.993±60.00 °C(Press: 760.00 Torr)(predicted)
- Dichte
- 1.468 · 1.468±0.10 g/cm3(Temp: 25 °C; Press: 760 Torr)(predicted)
- storage temp.
- -20 °C · Store at -20°C
- Löslichkeit
- Soluble in DMSO
- pka
- 14.156 · 14.156±0.20(predicted)
- Aggregatzustand
- Solid
- Farbe
- White to light yellow
- InChIKey
- NBPVNGWRLGHULH-CSOWVJSESA-N
- SMILES
- N12[C@@]([H])([C@@H]([C@H](O)C)C1=O)SC(S[C@H]1CC[S@@](=O)C1)=C2C(OCOC(=O)C(CC)CC)=O
Chemie und Industrie
Pharmakologische Informationen
Protein BindingSulopenem is minimally (~11%) protein-bound in plasma.
Pharmacodynamics
Sulopenem, similar to other beta-lactam antibacterials, exhibits time-dependent bacterial inhibition. The percentage of time that unbound plasma concentrations of sulopenem exceed the sulopenem minimum inhibitory concentration (MIC) against the infecting organism has been shown to best correlate with efficacy in _in vitro_ models of infection. In E. coli_, sulopenem demonstrated binding affinity for PBPs in the following order: PBP2 > PBP1A > PBP1B > PBP4 > PBP3 > PBP5/6.
Mechanism of Action
Sulopenem has _in vitro_ activity against gram-positive and gram-negative aerobic and anaerobic bacteria. The bactericidal activity of sulopenem results from the inhibition of cell wall synthesis and is mediated through sulopenem binding to penicillin binding proteins (PBPs). Sulopenem's β-lactam ring alkylates the serine residues of PBPs, ultimately inhibiting peptidoglycan cross-linking.
Biological Half-LifeIn the fasted state, the mean elimination half-life of sulopenem is 1.18 hours. When administered with a high-fat meal, the mean elimination half-life is 1.28 hours.
Metabolism/Metabolites
After oral administration, sulopenem etzadroxil is hydrolyzed via esterases to the active [sulopenem], which is further metabolized via hydrolysis and then dehydrogenation. Two inactive metabolites of sulopenem have been identified - M1a and M1b - which accounted for 21.8% and 43.6%, respectively, of circulating radioactivity following the administration of a radiolabeled dose.
Absorption, Distribution and Excretion
Following rapid conversion into the active moiety, sulopenem bioavailability is approximately 40% in the fasted state, increasing to 64% when administered with a meal.
Following a single oral dose of radiolabeled sulopenem etzadroxil in healthy adult subjects, 44.3% of radioactive product was recovered in the feces (26.9% as unchanged sulopenem) and 40.8% was recovered in the urine (3.1% as unchanged sulopenem).
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