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

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

Uses

Used in Pharmaceutical Industry:
Cefazolin is used as an antibacterial agent for systemic infections. It is effective in treating a wide range of bacterial infections due to its ability to disrupt bacterial cell wall synthesis, leading to cell lysis and death. Its longer half-life and lower irritation upon injection make it a preferred choice in the treatment of various infections.
Additionally, Cefazolin's chemical properties, such as its needle-like structure, may have potential applications in other industries, although the provided materials do not specify any such uses.

Originator

Cefamedin,Fujisawa,Japan,1971

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

• 27164-46-1 cefazolin sodium 
• 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 
• 43194-95-2 C₈H₁₂N₄O₃ 
• 61-24-5 cephalosporin C 
• 957-68-6 7-Aminocephalosporanic acid 
• 55633-19-7 (1H-tetrazol-1-yl)-2-acetic acid methyl ester 
• 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 
• 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

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

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.

Modulation of the microenvironment surrounding the active site of penicillin g acylase immobilized on acrylic carriers improves the enzymatic synthesis of cephalosporins

The catalytic properties of penicillin G acylase (PGA) from Escherichia coli in kinetically controlled synthesis of β-lactam antibiotics are negatively affected upon immobilization on hydrophobic acrylic carriers. Two strategies have been here pursued to improve the synthetic performance of PGA immobilized on epoxy-activated acrylic carriers. First, an aldehyde-based spacer was inserted on the carrier surface by glutaraldehyde activation (immobilization yield = 50%). The resulting 3-fold higher synthesis/hydrolysis ratio (vs/vh1 = 9.7 ± 0.7 and 10.9 ± 0.7 for Eupergit C and Sepabeads EC-EP, respectively) with respect to the unmodified support (vs/vh1 = 3.3 ± 0.4) was ascribed to a facilitated diffusion of substrates and products as a result of the increased distance between the enzyme and the carrier surface. A second series of catalysts was prepared by direct immobilization of PGA on epoxy-activated acrylic carriers (Eupergit C), followed by quenching of oxiranes not involved in the binding with the protein with different nucleophiles (amino acids, amines, amino alcohols, thiols and amino thiols). In most cases, this derivatization increased the synthesis/hydrolysis ratio with respect to the non derivatized carrier. Particularly, post-immobilization treatment with cysteine resulted in about 2.5-fold higher vs/vh1 compared to the untreated biocatalyst, although the immobilization yield decreased from 70% (untreated Eupergit C) to 20%. Glutaraldehydeand cysteine-treated Eupergit C catalyzed the synthesis of cefazolin in 88% (±0.9) and 87% (±1.6) conversion, respectively, whereas untreated Eupergit C afforded this antibiotic in 79% (±1.2) conversion.

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.

Preparation method of cefazolin sodium with previous research quality and medicine preparation of cefazolin sodium

The invention discloses a preparation method of cefazolin sodium with previous research quality. The preparation method is characterized by comprising the following steps: (1) adding a boron trifluoride-dimethyl carbonate solution into dimethyl carbonate; stirring and adding 2-sulfydryl-5-methyl-1,3,4-thiadiazole and 7-ACA (Acetic Acid) to react; after the reaction is finished, adding dimethyl formamide and dropwise adding hydrochloric acid; adjusting the temperature to 25 to 35 DEG C and reacting for 60 minutes; filtering and washing with acetone; drying in vacuum to obtain a TDA (Toluene Diamine) crude product; (2) preparing mixed anhydride from dichloromethane, tetrazolyl acetic acid, triethylamine and pivaloyl chloride; (3) adding the TDA crude product into a dichloromethane solvent; cooling and dropwise adding tetramethyl guanidine; dropwise adding the mixed anhydride to react, and purifying and refining a crystal through a low-temperature acetonitrile-water extraction process after extraction and crystallization. With the adoption of the preparation method provided by the invention, the moisture content of the product can be reduced and residues of the solvent can be reduced; the increasing of related substances can be effectively reduced, a freeze-drying technology is not used and the production efficiency is improved.

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.

PROCESS FOR PRODUCING γ(b)-LACTAM DERIVATIVES

A process for preparing a β-lactam derivative represented by the formula (2)A-COOH wherein A is a residue of the β-lactam derivative, the process being characterized in that a β-lactam derivative having a protected carboxyl group which derivative is represented by the formula (1)A-COO-X wherein A is as defined above and X is a benzyl group which may have an electron-donating group as a substituent on a phenyl ring or a diphenylmethyl group which may have an electron-donating group as a substituent on a phenyl ring, is treated with aluminum halide in an aliphatic ether solvent to give the derivative of the formula (2); and that the removed group X can be recovered as X-OH for reuse.

Process for the preparation of new intermediates useful in the synthesis of cephalosporins

Cefazolin, cefazedone, cefoperazone, cefamandole, cefatrizine or ceftriaxone is prepared by reacting glutaryl 7-ACA of the formula: STR1 with a compound of formula (II): wherein R is 5-methyl-1,3,4-thiadiazol-2-yl, 1H-1,2,3-triazol-4-yl, 1-methyl-tetrazol-5-yl or 1,2,5,6-tetrahydro-2-methyl-5,6-dioxo-1,2,4-triazin-3-yl group, and R1 and R2 are both hydrogen and the other is an acyl group, in an aqueous solution in an amount of 3-5 mols per mol of glutaryl 7-ACA to about 90° C. and for a time from about 2 to about 10 hours; optionally recovering the excess of the compound of formula (II), thereby preparing a compound of formula (III) in an aqueous solution: STR2 wherein R is as above defined and optionally deacylating said compound of formula (III); and converting the resulting compound of formula (I) STR3 wherein R, R1 and R2 are as defined above in the presence of a non-chlorinated solvent into one of said cephalosporins.

Dimethyl formiminium chloride chlorosulphate derivatives useful as intermediates for producing cephalosporins

This invention relates to reactive derivatives of 2-(2-aminothiazol-4-yl)-2-methoxyimino acetic acid and 1H-tetrazol-1-acetic acid of the following general formula I, STR1 wherein R3 = STR2 as well as to use thereof in the manufacture of cephalosporin antibiotics such as cefotaxime, ceftriaxone and cefazolin.

Process for the preparation of new intermediates useful in the synthesis of cephalosporins

There is disclosed a new process for the preparation of a compound of formula I: ???wherein R is a heterocyclic group which contains at least a nitrogen atom with or without a sulphur or oxygen atom and R1and R2are both hydrogen atoms or one of them is a hydrogen atom and the other is an acyl group; which comprises the condensation of glutaryl 7-ACA with a compound of formula R-SH, wherein R is as above defined; the compounds obtained are new intermediates useful for the preparation of important cephalosporins.

Method for manufacture of cephalosporins and intermediates thereof

This invention relates to reactive derivatives of 2-(2-aminothiazol-4-yl)-2-methoxyimino acetic acid and 1H-tetrazol-1-acetic acid of the following general formula I, whereinR3= as well as to use thereof in the manufacture of cephalosporin antibiotics such as cefotaxime, ceftriaxone and cefazolin.