63527-52-6 Usage
Description
Like other third-generation
cephalosporins, it has excellent anti-Gram-negative activity and is useful institutionally. It has a
metabolically vulnerable acetoxy group attached to C-3 and loses approximately 90% of its activity when this
is hydrolyzed. This metabolic feature also complicates the pharmacokinetic data, because both active forms
are present and have different properties. Cefotaxime should be protected from heat and light and may color
slightly without significant loss of potency. Like other third-generation cephalosporins, cefotaxime has less
activity against staphylococci but has greater activity against Gram-negative organisms.
Uses
Different sources of media describe the Uses of 63527-52-6 differently. You can refer to the following data:
1. Cefotaxime has a broad spectrum of antibicrobial use. It acts bactericidally. It is highly
active with respect to Gram-negative microorganisms (E. coli, Citrobacter, Proteus
mirabilis, P. indole, Providencia, Klebsiella, Serratia), and a few strains of Pseudomonas,
H. influenzae that are resistant to other antibiotics. Cefotaxime is less active with respect
to streptococci, pneumococci, meningococci, gonococci, and bacteroides. It is resistant to
the majority of beta-lacatamases of Gram-positive and Gram-negative microorganisms.
This drug is used for severe bacterial infections caused by microorganisms that are sensitive to the drug such as peritonitis, sepsis, abdominal infections, infections of the pelvis
minor, infections of the lower respiratory tract, urinary tract, bones, joints, skin, soft tissues,
and infected wounds and burns. Synonyms of this drug are claforan, zarivis, and others.
2. Cefotaxime is an antibiotic with broad spectrum activity against Gram positive and Gram negative bacteria.
Therapeutic Function
Antibiotic
Antimicrobial activity
The aminothiazoyl and methoximino groups at the 7-amino
position confer, respectively, potent activity against many
Gram-negative rods and cocci and stability to
most β-lactamases. Ps. aeruginosa, Sten. maltophilia and other
pseudomonads are often resistant. Brucella melitensis and some
strains of Nocardia asteroides are susceptible. Activity against
L. monocytogenes and B. fragilis is poor.
Acquired resistance
Many enterobacteria resistant to other b-lactam agents are
susceptible, but selection of resistant strains with derepressed
chromosomal molecular class C cephalosporinases may occur. Gram-negative bacilli producing variants
of the TEM enzymes (pp. 230–231) are resistant.
Pharmacokinetics
Cmax 500 mg intramuscular: 10–15 mg/L after 0.5–1 h
1 g intravenous (15-min infusion): 90 mg/L end infusion
Plasma half-life: c.1 h
Volume of distribution: 32–37 L
Plasma protein binding: c. 40%
Distribution
It is widely distributed, achieving therapeutic concentrations
in sputum, lung tissue, pleural fluid, peritoneal fluid, prostatic
tissue and cortical bone. In patients receiving 2 g every
8 h, mean CSF concentrations in aseptic meningitis were 0.8 mg/L. Levels of 2–15 mg/L can be found in the CSF
in the presence of inflammation after doses of 50 mg/kg by
intravenous infusion over 30 min. A single intraventricular
dose of 40 mg/kg produced levels at 2, 4 and 6 h of 6.4, 5.7
and 4.5 mg/L, respectively.
Metabolism
About 15–25% of a dose is metabolized by hepatic esterases to
the desacetyl form, which may have some clinical importance
because of its concentration in bile and accumulation in renal
failure. Desacetylcefotaxime has about 10% of the activity of
the parent against enterobacteria, less against Staph. aureus.
Its half-life in normal subjects is around 1.5 h.
Excretion
Elimination is predominantly by the renal route, more than
half the dose being recovered in the urine over the first 24 h,
about 25% as the desacetyl derivative. Excretion is depressed
by probenecid and declines in renal failure with accumulation
of the metabolite. In patients with creatinine clearances in the
range 3–10 mL/min, the plasma half-life rose to 2.6 h while
that of the metabolite rose to 10 h.
Clinical Use
Cefotaxime is widely used in neutropenic patients, respiratory
infection, meningitis, intra-abdominal sepsis, osteomyelitis,
typhoid fever, urinary tract infection, neonatal sepsis and
gonorrhea.
Side effects
Minor hematological and dermatological side effects common
to group 4 cephalosporins have been described.
Superinfection with Ps. aeruginosa in the course of treatment
has occurred. Occasional cases of pseudomembranous colitis
have been reported.
Synthesis
Cefotaxime, α-O-methyloxime acetate (6R, 7R)-7-[2-(2-amino-4-thiazolyl)-
glyoxylamido]-3-(hydroxymethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-2-carboxylic
acid (32.1.2.56), is synthesized by acylating of 7-aminocephalosporanic acid with 2-(2-amino-
4-thiazolyl)-2-methoxyiminoacetic acid, which is protected at the amino group by a trityl protection (32.1.2.54). After removing the trityl protection from the resulting product (32.1.2.55)
with dilute formic acid, the desired cefotaxime (32.1.2.56) is formed. The ethyl ester of 2-(2-
amino-4-thiazolyl)-2-methoxyminoacetic acid necessary for this synthesis, as well as for the
synthesis of a number of other antibiotics of the cephalosporin series, is synthesized from acetoacetic ester. Nitrosation of acetoacetic ester with nitrous acid gives isonitrosoacetoacetic
ester (32.1.2.49). O-Methylation of the hydroxyl group of obtained product with dimethylsulfate in the presence of potassium carbonate gives ethyl 2-(methoxyimino)acetoacetate
(32.1.2.50).Brominating the resulting product with bromine in methylene chloride in the presence of p-toluenesulfonic acid gives 4-bromo-2-methoxyiminoacetoacetic ester (32.1.2.51).
Reacting this with thiourea according to the classic scheme of preparing of thiazoles from α-
bromocarbonyl compounds and thioamides gives the ethyl ester of 2-(2-amino-4-thiazolyl)-2-
methoxyiminoacetic acid (32.1.2.52). Reacting this with triphenylchloromethane in the
presence of triethylamine results in a trityl protection of the amino group, forming the ethyl
ester of 2-(2-tritylamino-4-thiazolyl)-2-methoxyminoacetic acid (32.1.2.52), which is
hydrolyzed to the acid (32.1.2.54) using sodium hydroxide. The resulting acid (32.1.2.54), as
was already stated, is used for acylating of 7-aminocephalosporanide acid in the presence of
dicyclohexylcarbodiimide, giving tritylated cefotaxime, α-O-methyloxime acetate 7-[2-(2-
tritylamino)-4-thiazolyl-glycoxylamido]-3-(hydroxymethyl)-8-oxo-5-thia-1-azabicyclo
[4.2.0]oct-2-en-2-carboxylic acid (32.1.2.55). Finally, removing the trityl protection from the
synthesized product (32.1.2.55) using dilute formic acid gives cefotaxime (32.1.2.56).
Metabolism
After partial metabolism in the liver to
desacetylcefotaxime and inactive metabolites, elimination
is mainly by the kidneys and about 40-60% of a dose has
been recovered unchanged in the urine within 24 hours;
a further 20% is excreted as the desacetyl metabolite.
Relatively high concentrations of cefotaxime and
desacetylcefotaxime occur in bile and about 20% of a dose
has been recovered in the faeces.
Probenecid competes for renal tubular secretion with
cefotaxime resulting in higher and prolonged plasma
concentrations of cefotaxime and its desacetyl metabolite
Check Digit Verification of cas no
The CAS Registry Mumber 63527-52-6 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 6,3,5,2 and 7 respectively; the second part has 2 digits, 5 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 63527-52:
(7*6)+(6*3)+(5*5)+(4*2)+(3*7)+(2*5)+(1*2)=126
126 % 10 = 6
So 63527-52-6 is a valid CAS Registry Number.
InChI:InChI=1/C16H17N5O7S2/c1-6(22)28-3-7-4-29-14-10(13(24)21(14)11(7)15(25)26)19-12(23)9(20-27-2)8-5-30-16(17)18-8/h5,10,14H,3-4H2,1-2H3,(H2,17,18)(H,19,23)(H,25,26)/b20-9-/t10-,14-/m0/s1
63527-52-6Relevant articles and documents
Cefotaxime sodium pharmaceutical preparation, and application thereof in treatment of new salmonella infection indications including typhoid and paratyphoid
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Paragraph 0169-0189, (2020/09/20)
The invention provides a cefotaxime sodium, and a preparation method, a cefotaxime sodium preparation and application thereof. The mass content of the cefotaxime sodium is 98% or above, and the cefotaxime sodium also comprises impurities A, B and C. The preparation method comprises the following steps: firstly, reacting methoxyiminoacetic acid with an activating agent to obtain an active ester intermediate; reacting 7-ACA with the active ester intermediate under a temperature control condition, and performing acid regulation and crystallization to obtain cefotaxime acid; carrying out a salifying reaction on cefotaxime acid and a salifying agent in a salifying solvent, and separating out to obtain the cefotaxime sodium. The cefotaxime sodium is low in impurity content, beneficial to long-term storage and placement, good in quality stability and better in clinical curative effect and safety, and can be used for treating salmonella infections including typhoid and paratyphoid.
1/4 water cefotaxime sodium compound
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Paragraph 0034; 0043; 0052, (2019/01/17)
The invention discloses a 1/4 water cefotaxime sodium compound and a preparation method thereof. The cefotaxime sodium per mole contains 1/4 mole of water. The 1/4 water cefotaxime sodium compound obtained has good particle size distribution, good fluidity, low impurity content, thermodynamic stability and wide application prospects.
PROCESS FOR PREPARATION OF CEFOTAXIME ACID
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Page/Page column 7, (2011/04/26)
Cefotaxime acid of formula (I) is prepared by using a kind of alcohol as the single solvent in presence of a base.
