Biapenem Chemical Properties

Melting point:

265-271°C (dec.)

alpha 

D20 -32.9° (c = 0.5)

storage temp. 

-20°C

solubility 

H2O: ≥5mg/mL (warmed)

form 

powder

color 

white to beige

InChI

InChI=1/C15H18N4O4S/c1-7-11-10(8(2)20)14(21)19(11)12(15(22)23)13(7)24-9-3-17-5-16-6-18(17)4-9/h5-11,20H,3-4H2,1-2H3/t7-,8-,10-,11-/s3

InChIKey

MRMBZHPJVKCOMA-YJFSRANCSA-N

SMILES

C(C1=C([C@H](C)[C@]2([H])[C@@]([H])([C@H](O)C)C(=O)N12)SC1C[N+]2=CN=CN2C1)(=O)[O-] |&1:3,5,7,9,r|

CAS DataBase Reference

120410-24-4(CAS DataBase Reference)

Safety Information

WGK Germany 

3

HS Code 

2941.90.5000

Biapenem Usage And Synthesis

New carbapenem antibiotic (carbapenem family members)

Biapenem, together with several drugs developed in different companies in the United State, Japan, and China, all belong to the rapid-developing carbapenem family members. It is white to yellowish white crystalline powder, and is a kind of carbapenem-class antibiotics for injection developed by both the Lederle Company in Japan and the Cyanamid Company in the united state in 1989. It has a broad antibacterial spectrum and has an excellent bactericidal effect on Gram-negative, Gram-positive, aerobic and anaerobic bacteria. The C1 position of its structure contains a 1β-methyl group which can enable drugs to be stable to the effects of the dehydropeptidase I (DHP-I) in the human kidney without the necessity to be combined with DHP-I inhibitor for therapy, and thus reducing its renal toxicity, and is also stable to β-lactamase stability; it also has excellent pharmacokinetic properties and low toxicity; It has excellent therapeutic effect on treating various diseases such as concurrent intra-abdominal infections, plastic surgery infections, gynecological infections, ENT infections, lower respiratory tract infections (including bacterial pneumonia), and also concurrent urinary tract infections with a good tolerance and a lower incidence of adverse reactions.
A notable feature of this product is the existence of the 1β-methyl carbapenem (containing bicyclic triazole) located at the S at 2-position. Structure-function relationship studies have showed that the presence of quaternary ammonium cation located in the side chain is the key that affects the outer membrane permeability, making the inhibitory effect of the product on Pseudomonas aeruginosa and anaerobic bacteria be 2 to 4 times as potent as that of imipenem, and the inhibitory effect on the drug-resistant Pseudomonas aeruginosa be 4 to 8 times as potent as that of meropenem, and moreover, making it more effective in treating Acinetobacter spp, anaerobic bacteria than ceftazidime. Thus, it is promising that it is expected to become a novel first-line drug for treating severe infection. The general dose for intravenously infusion of Biapenem is about 300mg with time being 30~60min at 2 times per day.

Antibacterial activity

Studies have shown that biapenem has broad-spectrum and potent antibacterial activity against G+ bacteria, G-as well as anaerobic bacteria, etc. MIC90 range of this product against 456 clinical isolates of G + bacteria was 0.006~3.13μg/ml; for 1145 G-bacteria, the MIC90 range is 0.1~3.13μg/ml with its antibacterial activity being 2 times as strong as imipenem; for most anaerobes, the MIC90 range is 0.05~1.56μg/ml. Biapenem has broad-spectrum antimicrobial activity. The antimicrobial activity of it is similar as that of imipenem and meropenem, and stronger than that latamoxef and ceftazidime. The MIC value and MBC values are ​​similar with each other for this drug. Upon MIC concentration, it can cause morphological changes of Pseudomonas aeruginosa and Escherichia coli; upon a concentration higher than MIC, the bacteria exhibits lytic phenomenon. Staphylococcus aureus, GPB, Streptococcus pyogenes and Streptococcus pneumoniae are highly sensitive to the drug; but methicillin-resistant Staphylococcus aureus and GPB are also resistant to this drug. In addition, this product also has excellent antibacterial activity against Bacteriodes fragilis also with MIC90 being 1.56μg /ml. The research of Ichiro Murakami has shown that this antibacterial activity against clinical isolates of G + bacteria and Enterobacteriaceae of this drug is similar as or slightly weaker than that of imipenem, but with a stronger anti-bacterial activity against Enterobacteriaceae family than imipenem; for non G-fermentation bacteria, especially Pseudomonas aeruginosa and GM-resistant Pseudomonas aeruginosa, this antibacterial activity of this drug is two times as strong as imipenem.
Biapenem has a high affinity to the protein PBP2 and PBP4 of Pseudomonas aeruginosa, exhibiting its excellent antibacterial activity and low endotoxin release property during the bactericidal process. In 2001, the study of Japanese Scholars (Hiraishi.T) had shown that the transient bactericidal action of biapenem against Pseudomonas aeruginosa PAO1 is superior to that of meropenem. In 2005, during the comparison of transient bactericidal effects against Pseudomonas aeruginosa for biapenem, imipenem, and meropenem, Japanese scholars (Shimauchi.C) found that biapenem has a best bactericidal activity within the same treatment time.
The above information is edited by the chemicalbook of Dai Xiongfeng.

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.

Intellectual property status

This product was developed by Lederle Company (Japan) and Cyanamid Company (The United States) in 1989, as a novel kind of 1β-methyl carbapenem antibiotics which entered into market in Japan in March 2002. After searching, the domestic development of this product doesn’t constitute infringement to the patents in other countries; there are also no administrative protection restrictions on it.

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.

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.

Chemical Properties

Off-White Solid

Originator

Wyeth (US)

Uses

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

Uses

An carbapenem antibacterial.

Uses

A carbepenem with antibacterial action

Definition

ChEBI: Biapenem is a carbapenem antibiotic in which the azetidine and pyrroline rings carry 1-hydroxymethyl and pyrazolo[1,2-a][1,2,4]triazolium-6-ylthio substituents respectively. It has a role as an antibacterial drug. It is a member of carbapenems, a pyrazolotriazole and an organic sulfide.

brand name

Omegacin

Antimicrobial activity

A semisynthetic carbapenem with a 2-substituted triazolium moiety. It has broad-spectrum activity against most aerobic and anaerobic Gram-positive and Gram-negative organisms. It is equivalent to, or slightly more active than, imipenem against Gram-negative aerobic bacteria and slightly less active than imipenem against Gram-positive organisms. It is stable to hydrolysis by dehydropeptidase. It is not hydrolyzed by most serine β-lactamases, but like all carbapenems and penems is readily hydrolyzed by carbapenemases. It penetrates into bronchial epithelial lining fluid with peak concentrations of 2.4–4.4 mg/L. The plasma half-life is 1.5–1.9 h. The potential for neurotoxicity is less than that of imipenem.

Biochem/physiol Actions

Biapenem is a broad spectrum, carbapenem-based antibiotic with activity against both Gram-positive and Gram-negative bacterial strains.

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.

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