25953-19-9

Basic information

• Product Name: Cefazolin
• Synonyms: CEFAZOLIN;CEFAZOLIN ACID;(6r-trans)-3-[[(5-methyl-1,3,4-thiadiazol-2-yl)thio]methyl]-8-oxo-7-[[(1h-tetr;5-thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylicacid,3-(((5-methyl-1,3,4-thia;7-(1-(1h-)-tetrazolylacetamido)-3-[2-(5-methyl-1,3,4-thiadiazolyl)thiomethyl]d;azol-1-yl)acetyl]-amino]-5-thia-1-azabicylo;cefamezin;CefazoilnV
• CAS NO: 25953-19-9
• Molecular Formula: C₁₄H₁₄N₈O₄S₃
• Molecular Weight: 454.51
• EINECS: 247-362-8
• Mol File: 25953-19-9.mol
• Article Data: 16

Chemical Properties

• Melting Point: 198-200 C
• Appearance: needle-like crystals
• Density: 2.01 g/cm³
• Refractive Index: 1.961
• Storage Temp.: Hygroscopic, -20°C Freezer, Under inert atmosphere
• Solubility: DMSO (Slightly), Methanol (Very Slightly, Heated)
• PKA: pKa 2.15 (Uncertain)
• Stability: Hygroscopic
• CAS DataBase Reference: Cefazolin(CAS DataBase Reference)
• NIST Chemistry Reference: Cefazolin(25953-19-9)
• EPA Substance Registry System: Cefazolin(25953-19-9)

Safety Data

• Hazard Codes: Xn
• Statements: 20/21/22-36/37/38
• Safety Statements: 26-36
• WGK Germany: 3
• Hazardous Substances Data: 25953-19-9(Hazardous Substances Data)

Usage

Description

Cefazolin has the natural acetyl side chain at C-3 replaced by a thio-linked thiadiazole ring. Although this group is an activating leaving group, the moiety is not subject to the inactivating host hydrolysis reaction that characterizes cephapirin. At C-7, it possesses a tetrazoylmethylene unit. Cefazolin is less irritating on injection than its cohort in this generation of drugs and has a longer half-life than cephapirin. Its dosing should be reduced in the presence of renal impairment. It is comparatively unstable and should be protected from heat and light.

Chemical Properties

needles

Originator

Cefamedin,Fujisawa,Japan,1971

Uses

Different sources of media describe the Uses of 25953-19-9 differently. You can refer to the following data:
1. Cefazolin is an antibacterial compound derived from 7-amino-cephalosporanic acid.
2. Antibacterial (systemic).

Definition

ChEBI: A cephalosporin compound having [(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]methyl and (1H-tetrazol-1-ylacetyl)amino side-groups.

Manufacturing Process

7-Aminocephalosporanic acid is converted to its sodium salt and acylated with 1H-tetrazole-1-acetyl chloride. The acetoxy group is then displaced by reaction with 5-methyl-1,3,4-thiadiazole-2-thiol in buffer solution. The product acid is converted to the sodium salt by NaHCO3.

Therapeutic Function

Antibacterial

Antimicrobial activity

Enterobacter, Klebsiella, Providencia, Serratia spp. and Pr. vulgaris are all resistant. B. fragilis is resistant, but other anaerobes are susceptible.

Pharmacokinetics

Distribution The volume of distribution is the smallest of the cephalosporins in group 1, perhaps an indication of relative confinement to the plasma space. It crosses inflamed synovial membranes, but the levels achieved are well below those of the simultaneous serum levels and entry to the CSF is poor. In patients receiving 10 mg/kg by intravenous bolus, mean concentrations in cancellous bone were 3.0 mg/kg when the mean serum concentration was 33 mg/L, giving a bone:serum ratio of 0.09. Some crosses the placenta, but the concentrations found in the fetus and membranes are low. Metabolism and excretion It is not metabolized. Around 60% of the dose is excreted in the urine within the first 6 h, producing concentrations in excess of 1 g/L. Excretion is depressed by probenecid. The renal clearance is around 65 mL/min and declines in renal failure, when the half-life may rise to 40 h, although levels in the urine sufficient to inhibit most urinary pathogens are still found. It is moderately well removed by hemodialysis and less well by peritoneal dialysis. Levels sufficient to inhibit a number of enteric organisms likely to infect the biliary tract are found in T-tube bile (17–31 mg/L after a 1 g intravenous dose), but this is principally due to the high serum levels of the drug and the total amounts excreted via the bile are small.

Clinical Use

Cefazolin has been widely used in surgical prophylaxis, especially in biliary tract (because of the moderately high concentrations achieved in bile), orthopedic, cardiac and gynecological surgery.

Side effects

Side effects are those common to other cephalosporins ,including rare bleeding disorders and encephalopathy in patients in whom impaired excretion or direct instillation leads to very high CSF levels. Neutropenia has been described and hypoprothrombinemic bleeding has been attributed to the side chain.

Synthesis

Cefazolin, (6R-trans)-3[[(5-methyl-1,3,4-thiadiazol-2-yl)thio]methyl]-8-oxo- 7-[(1H-tetrazol-1-ylacetyl)amino]-5-thia-1-azabycyclo[4.2.0]oct-2-en-2-carboxylic acid (32.1.2.7), is synthesized by reacting 7-aminocephalosporanic acid with a mixed anhydride (32.1.2.6), which is the result of a reaction of tetrazolylacetic acid with pivalic (trimethylacetic) acid chloride. Further reaction with 2-mercapto-5-methyl-1,3,4-thiadiazole results in a substitution of the 3-acetoxy group with a mercaptothiadiazol group, giving cefazolin (32.1.2.7).

InChI:InChI=1/C14H14N8O4S3/c1-6-17-18-14(29-6)28-4-7-3-27-12-9(11(24)22(12)10(7)13(25)26)16-8(23)2-21-5-15-19-20-21/h5,9,12H,2-4H2,1H3,(H,16,23)(H,25,26)/t9-,12-/m1/s1

Upstream product

• 32510-61-5 7-((tetrazol-1'-yl)acetylamino)-3-acetyloxymethyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid 
• 29490-19-5 2-mercapto-5-methyl-1,3,4-thiadiazole 
• 30246-33-4 (6R,7R)-7-amino-3-(5-methyl-1,3,4-thiadiazol-2-ylthiomethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid 
• 55633-19-7 (1H-tetrazol-1-yl)-2-acetic acid methyl ester 
• 27164-46-1 cefazolin sodium 
• 43194-95-2 C₈H₁₂N₄O₃ 
• 61-24-5 cephalosporin C 
• 957-68-6 7-Aminocephalosporanic acid 
• 79239-19-3 delta-3 methyl ester of cefazolin 
• 98493-37-9 7-amino-3-<(5-methyl-1,3,4-thiadiazol-2-yl)thiomethyl>-Δ³-cephem-4-carboxylic acid hydrochloride 

Downstream Products

• 847354-98-7 Δ2-cefazolin diphenylmethyl ester 
• 55633-22-2 Δ3-cefazolin diphenylmethyl ester 
• 79239-19-3 delta-3 methyl ester of cefazolin 
• 27164-46-1 cefazolin sodium 

Relevant articles and documents

Chemoenzymatic one-pot synthesis of cefazolin from cephalosporin C in fully aqueous medium, involving three consecutive biotransformations catalyzed by D-aminoacid oxidase, glutaryl acylase and penicillin G acylase

A new chemoenzymatic synthesis of Cefazolin through the correct assembly of three biotransformations catalyscd by D-aminoacid oxidase, glutaryl acylase and penicillin G acylase is described. This multienzymatic synthesis has been performed from the natural Cephalosporin C in fully aqueous medium without intermediate purification stages. Almost quantitative yields have been achieved in all the enzymatic reactions.

Cefazolin sodium or composition thereof, preparation method thereof, preparations thereof and novel indication for genital system infection

The present invention provides cefazolin sodium or a composition thereof, a preparation method thereof, preparations thereof and use. The preparation method has high repeatability and a stable and reliable production process. The prepared cefazolin sodium or the composition thereof has a low impurity content, facilitating improvement in raw material quality and quality of corresponding preparations, and improvement in safety and clinical curative effects of preparations. The cefazolin sodium or the composition thereof can be used for preparing medicines treating genital system infection.

ORAL NEUROTHERAPEUTIC CEFAZOLIN COMPOSITIONS

The treatment of neurological disorders using cefazolin compositions and pharmaceutical compositions including oral dosage forms that include cefazolin compositions are described.