Biapenem

Base Information

• Chemical Name: Biapenem
• CAS No.: 120410-24-4
• Deprecated CAS: 103939-78-2,133279-57-9
• Molecular Formula: C15H18N4O4S
• Molecular Weight: 350.398
• UNII: YR5U3L9ZH1
• DSSTox Substance ID: DTXSID5046435
• Nikkaji Number: J550.678F
• Wikipedia: Biapenem
• Wikidata: Q4902548
• NCI Thesaurus Code: C72620
• Metabolomics Workbench ID: 53004
• ChEMBL ID: CHEMBL285347
• Mol file: 120410-24-4.mol

Synonyms:3-((6,7-dihydro-5H-pyrazolo(1,2-a)(1,2,4)triazol-4-ium-6-yl)thio)-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo(3,2,0)hept-2-ene-2-carboxylate;biapenem;CLI 86,815;CLI 86815;CLI-86815;L 627;L-627;LJC 10627;LJC-10627;LJC10,627

Chemical Property of Biapenem

Chemical Property:

• Appearance/Colour: White to light yellow powder
• Melting Point: 265-271°C (dec.)
• Refractive Index: 1.651
• PSA: 127.67000
• LogP: -1.95710
• Storage Temp.: -20?C Freezer
• Solubility.: H2O: ≥5mg/mL (warmed)
• XLogP3: 1.4
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 3
• Exact Mass: 350.10487624
• Heavy Atom Count: 24
• Complexity: 609

Purity/Quality:

99% ^*data from raw suppliers

Biapenem ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC1C2C(C(=O)N2C(=C1SC3CN4C=NC=[N+]4C3)C(=O)[O-])C(C)O
• Isomeric SMILES: C[C@@H]1[C@@H]2[C@H](C(=O)N2C(=C1SC3CN4C=NC=[N+]4C3)C(=O)[O-])[C@@H](C)O
• Recent ClinicalTrials: Clinical Efficacy of Combination Therapy Based on High-dose Biapenem in CRKP Infections
• Recent NIPH Clinical Trials: Feasibility and efficacy of the de-escalation therapy by Biapenem for postoperative bacterial pneumonia.
• Indications: Sensitive strains of the drugs include: Staphylococcus aureus, Streptococcus pneumoniae, Enterococcus (except enterococci faecium), Moraxella, Escherichia coli, Citrobacter, Klebsiella, Enterobacter, Serratia, Proteus, Haemophilus influenzae, Pseudomonas aeruginosa, Actinomyces, Peptostreptococcus, Bacteroides, Prevotella, Fusobacterium spp. This product is suitable for treating sensitive bacteria induced treatment sepsis, pneumonia, lung abscess, secondary infection caused by chronic respiratory disease, intractable cystitis, pyelonephritis, peritonitis, complicated cystitis, uterus annex inflammation, and gynecological annex inflammation go far.
• Uses: 1. It is a kind of total synthesis gatifloxacin antibacterial drug. 2. Biapenem is a kind of carbapenem synthetic antibiotic. Its salt form is white or off-white powder. It is soluble in water, but insoluble in common organic solvents. It is more stable to the action of renal dehydropeptidase than meropenem and is not necessary to be combined with the enzyme inhibitor. It can fight against gram-negative bacteria, especially with a stronger antibacterial activity against Pseudomonas aeruginosa than imipenem; the antibacterial activity against aerobic Gram-positive bacteria is slightly lower than that of imipenem; its anti-anaerobe activity is the same as imipenem. Biapenem is a carbapenem antibiotic. It has in vitro activity against anaerobes. Biapenem is a new parenteral carbapenem antibacterial agent with a broad spectrum of in vitro antibacterial activity encompassing many Gram-negative and Gram-positive aerobic An carbapenem antibacterial. A carbepenem with antibacterial action
• Description: Biapenem was introduced in Japan as a parenteral treatment for bacterial infections. This new 1-β-methylcarbapenem can be prepared by reaction of commercially available 4-nitrobenzyl protected β-methylcarbapenem enolphosphate with mercapto bicyclotriazolium chloride, obtained in 11 steps starting from hydrazine, followed by deprotection of the carboxylic acid function. Biapenem is a bacterial cell wall synthesis inhibitor with a broad spectrum in vitro antibacterial activity encompassing many Gramnegative and Gram-positive aerobic and anaerobic bacteria, including species producing β-lactamases. Like imipenem, biapenem is moderately active against fnferococcus faecalis and E. faecuirn and is inactive against methicillin-resistant Staphylococcus aureus. Biapenem is stable to hydrolysis by human renal dihydropeptidase I (DHP-I) and therefore does not require the coadministration of a DHP-I inhibitor. In clinical trials, biapenem showed good clinical and microbiological efficacy in the treatment of patients with intraabdominal, lower respiratory tract and complicated urinary tract infections. After intravenous administration, the drug is widely distributed, has linear pharmacokinetics and is mainly excreted in the urine with an elimination half-life of approximately 1 h. Biapenem is generally well tolerated, the most common adverse events being skin eruptions/rashes, nausea and diarrhea.
• Clinical Use: Biapenem is a newer second-generation carbapenem withchemical and microbiological properties similar to those ofmeropenem. Thus, it has broad-spectrum antibacterial activitythat includes most aerobic Gram-negative and Grampositivebacteria and anaerobes. Biapenem is stable toDHP-I67 and resistant to most β-lactamases. It is claimedto be less susceptible to metallo-β-lactamases than eitherimipenem or meropenem. It is not active orally.

Technology Process of Biapenem

There total 10 articles about Biapenem which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 80.0%

6-[[(4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-2-(((4-nitrobenzyl)oxy)carbonyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-3-yl]thio]-6,7-dihydro-5H-pyrazolo[1,2-a][1,2,4]triazol-4-ium chloride → biapenem (120410-24-4)

Guidance literature:

With zinc; In phosphate buffer; at 20 ℃; for 1h; pH=5.6;

DOI:10.1021/jo980462j

Reference yield:

p-nitrobenzyl (4R,5S,6S)-3-(6,7-dihydro-5H-pyrazolo[1,2-a][1,2,4]triazol-8-ium-6-ylsulfanyl)-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate → biapenem (120410-24-4)

Guidance literature:

With palladium on activated charcoal; hydrogen; In tetrahydrofuran; at 5 - 10 ℃; pH=7-8;

Reference yield:

4-[(4R,5S,6S)-2-Carboxy-6-((R)-1-hydroxy-ethyl)-4-methyl-7-oxo-1-aza-bicyclo[3.2.0]hept-2-en-3-ylsulfanyl]-pyrazolidine-1,2-dicarboxylic acid → biapenem (120410-24-4)

Guidance literature:

With sodium hydroxide; ethyl formimidate hydrochloride; In tetrahydrofuran; water; at 0 ℃; for 0.0833333h; Yield given;

DOI:10.1021/jo00041a033

upstream raw materials:

(4-nitrophenyl)methyl (4R,5R,6S)-3-[(diphenoxyphosphinyl)oxy]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate

4-nitrobenzyl (4R,5R,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-3,7-dioxo-1-azabicyclo[3.2.0]-heptane-2-carboxylate

p-Nitrobenzyl (1R,5S,6S)-2-<<(N,N-Bis(p-nitrobenzyloxycarbonyl)pyrazolidin-4-yl>thio>-6-<(1R)-1-hydroxyethyl>-1-methylcarbapen-2-em-3-carboxylate

Refernces

• 1、 -. "AN IMPROVED PROCESS FOR THE PREPARATION OF CARBAPENEM ANTIBIOTIC". Page/Page column 8. . Retrieved 2013/09/26.
• 2、 Wildonger,Ratcliffe. "Heteroaryliumthio substituted carbapenem derivatives: Synthesis and in vitro activity of 1β-methyl-2-(dihydropyrrolotriazoliumthio)carbapenems". . p. 1866 - 1882. Retrieved 2007/10/02.