68401-81-0 Usage
Uses
Used in Pharmaceutical Industry:
Ceftizoxime is used as an antibacterial agent for treating various bacterial infections, including:
1. Lower respiratory tract infections: Ceftizoxime is effective in combating bacterial infections in the lungs and respiratory system.
2. Urinary tract infections: It is utilized to treat infections affecting the urinary system, such as those in the kidneys, bladder, and ureters.
3. Bone and joint infections: Ceftizoxime is employed to address bacterial infections in bones and joints, helping to alleviate pain and inflammation.
4. Skin and soft tissue infections: This antibiotic is used to treat skin and soft tissue infections, such as cellulitis and abscesses, by targeting the causative bacteria.
5. Abdominal infections: Ceftizoxime is also used to treat bacterial infections in the abdominal region, including those affecting the intestines and other internal organs.
Originator
Eposelin,Fujisawa,Japan,1982
Manufacturing Process
Phosphorus oxychloride (2.0 g) was added at one time at 5°C to 10°C to a
suspension of 2-methoxyimino-2-(2-amino-1,3-thiazol-4-yl)acetic acid (syn
isomer) (2 g) in dry ethyl acetate (20 ml). After stirring for 20 minutes at 7°C
to 10°C, bis(trimethylsilyl)acetamide (0.4 g) was added thereto at the same
temperature. After stirring for 10 minutes at 7°C to 10°C, phosphorus
oxychloride (2.0 g) was dropwise added thereto at the same temperature. The
resulting mixture was stirred for 10 minutes at 7°C to 10°C, and dry
dimethylformamide (0.8 g) was dropwise added thereto at the same
temperature. The mixture was stirred for 30 minutes at 7°C to 10°C to give a
clear solution. On the other hand, trimethylsilylacetamide (7.35 g) was added
to a suspension of 7-aminocephalosporanic acid (2.45 g) in dry ethyl acetate
(8 ml), after which the mixture was stirred at 40°C to give a clear solution.
To this solution was added at one time the above-obtained ethyl acetate
solution at -15°C, and the resulting mixture was stirred for 1 hour at -10°C to
-15°C. The reaction mixture was cooled to -30°C, and water (80 ml) was
added thereto. The aqueous layer was separated, adjusted to pH 4.5 with
sodium bicarbonate and subjected to column chromatography on Diaion HP-20
resin (Mitsubishi Chemical Industries Ltd.) using 25% aqueous solution of
isopropyl alcohol as an eluent. The eluate was lyophilized to give 7-[2-
methoxyimino-2-(2-amino-1,3-thiazol-4-yl)acetamido]cephalosporanic acid
(syn isomer) (1.8 g), MP 227°C (decomp.).
Therapeutic Function
Antibacterial
Antimicrobial activity
A semisynthetic cephalosporin supplied as the sodium salt. The
properties are very similar to those of cefotaxime, but it lacks
the acetoxymethyl group at position C-4 and is therefore not
subject to deacetylation. Activity against common pathogenic
bacteria (Table 13.4) is very similar to that of cefotaxime.
A 500 mg intramuscular injection achieves a plasma concentration
of around 14 mg/L. A concentration of 85–90 mg/L
is produced 30 min at the end of a 30-min intravenous infusion.
The plasma half-life is 1.3–1.9 h. Protein binding is
30%. It is well distributed. In children with meningitis receiving
200–250 mg/kg per day in four equally divided doses for
14–21 days, mean CSF concentrations 2 h after a dose were
6.4 mg/L on day 2 and 3.6 mg/L on day 14.
About 70–90% of the dose is recovered in the urine in the first
24 h, principally by glomerular filtration. Probenecid increases
the plasma half-life by about 50%. In patients receiving 1 g
intravenously over 30 min, the plasma elimination half-life rose
to 35 h when the corrected creatinine clearance was <10 mL/
min. It is partly removed by peritoneal and hemodialysis.
Adverse reactions and clinical use are similar to those of
cefotaxime.
Synthesis
Ceftizoxime, α-O-methyloxime of (6R,7R)-7-[2-(2-amino-4-thiazolyl)glyoxylamido]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-2-carboxylic acid (32.1.2.64), is synthesized by the scheme described below, which begins with 4-nitrobenzyl ester of
3-hydroxy-7-(2-phenylacetamido)-3-cefem-4-carboxylic acid (32.1.2.57), which is synthesized using a number of methods used to synthesize cefaclor (32.1.2.48). Reducing the C3–C4
double bond in the initial 4-nitrobenzyl ester of 3-hydroxy-7-(2-phenylacetamido)-3-cefem-
4-carboxylic acid (32.1.2.57) with sodium borohydride in methanol, 4-nitrobenzyl ester of
3-hydroxy-7-(2-phenylacetamido)-3-cefam-4-carboxylic acid (32.1.2.58) is obtained, the
hydroxyl group in which it is acylated by acetic anhydride in pyridine, forming acetate
(32.1.2.59). Reacting this with triethylamine removes a molecule of acetic acid, giving the
4-nitrobenzyl ester of 7-(2-phenylacetamido)-3-cefem-4-carboxylic acid (32.1.2.60).
Reacting this with phosphorous pentachloride in pyridine, followed by subsequent methanolysis deacylates the amide fragment of the molecule, giving the 4-nitrobenzyl ester of 7-amino-
3-cefem-4-carboxylic acid (32.1.2.61). Preliminary silylation of the amino group of this
compound with trimethylsilylacetamide and subsequent acylation with 2-(2-formamido-4-thiazolyl)-2-methoxyminoacetic acid chloride synthesized directly in reaction conditions by
reacting with phosphorous chloroxide in dimethylformamide gives the 4-nitro-benzyl ester of
α-O-methyloxime of 7-[2-(2-formamido-4-thiazolyl)glyoxylamido]-8-oxo-t-thia-1-azabicyclo[4.2.0]oct-2-en-2-carboxylic acid (32.1.2.62). Reducing this with hydrogen using a palladium on carbon catalyst removes the 4-nitrobenzyl protection from the carboxyl group,
forming the acid (32.1.2.63). Finally, hydrolysis of the formamide region of the molecule
using hydrogen chloride in methanol gives the desired ceftizoxime (32.1.2.64).
Check Digit Verification of cas no
The CAS Registry Mumber 68401-81-0 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 6,8,4,0 and 1 respectively; the second part has 2 digits, 8 and 1 respectively.
Calculate Digit Verification of CAS Registry Number 68401-81:
(7*6)+(6*8)+(5*4)+(4*0)+(3*1)+(2*8)+(1*1)=130
130 % 10 = 0
So 68401-81-0 is a valid CAS Registry Number.
InChI:InChI=1/C13H13N5O5S2/c1-23-17-7(5-4-25-13(14)15-5)9(19)16-8-10(20)18-6(12(21)22)2-3-24-11(8)18/h2,4,8,11H,3H2,1H3,(H2,14,15)(H,16,19)(H,21,22)/b17-7-
68401-81-0Relevant articles and documents
Preparation method of ceftizoxime sodium and preparation method of ceftizoxime sodium intermediate
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Paragraph 0037; 0045-0050, (2021/02/06)
The invention belongs to the technical field of medicines, and particularly relates to a preparation method of ceftizoxime sodium and a preparation method of a ceftizoxime sodium intermediate. The preparation method of ceftizoxime sodium comprises the following steps of: adding 7-amino-3-cephalosporin-free 4-carboxylic acid diphenyl methyl ester and (E)- 2-(2-aminothiazole-4-yl)-2-(methoxyimino) acetic acid into a DMF solution, adding a condensing agent, reacting completely, adding water into the reaction solution, filtering to obtain ceftizoxime sodium intermediate filtrate, adding acid to adjust pH, and filtering and drying to obtain ceftizoxime acid; and suspending the ceftizoxime acid in water, adding sodium bicarbonate, adding activated carbon after dissolution of sodium bicarbonate,filtering to obtain filtrate, adding acetone, crystallizing, filtering and drying to obtain ceftizoxime sodium. According to the method, 7-amino-3- cephalosporin-free-4-carboxylic acid diphenyl methylester and (E)-2-(2-aminothiazole-4-yl)-2-(methoxyimino) acetic acid are directly condensed, a diphenyl methyl ester protecting group is removed by a one-step method, the process is safe and environment-friendly, the raw materials are low in price, and the quality of the obtained ceftizoxime sodium is superior to that of the ceftizoxime sodium prepared by the traditional process.
Synthesis method of ceftizoxime acid
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Paragraph 0022-0033, (2019/04/04)
The invention discloses a synthesis method of ceftizoxime acid, and belongs to the technical field of pharmaceutical synthesis. According to the method, 7-ANCA and AE active ester react, so as to formthe ceftizoxime acid. The synthesis method has the advantages that the method is simple, reaction is easy to operate, the yield and purity are high, and by-products are less, and the method is suitable for industrial production.
A one-head spore zuozuo wo sodium compound (by machine translation)
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Paragraph 0027; 0028; 0034, (2019/01/17)
The present invention discloses a one-head spore zuozuo wo sodium compound, per mole of ceftizoxime sodium containing 1 mole water. The corresponding X-ray characteristic diffraction peaks of the 2 θ angle of the 11.43 ± 0.2 °, 13 . 24 ± 0.2 °, 16 . 54 ± 0.2 °, 17 . 86 ± 0.2 °, 19 . 45 ± 0.2 °, 20 . 66 ± 0.2 °, 22 . 33 ± 0.2 °, 22 . 88 ± 0.2 °, 23 . 29 ± 0.2 °, 23 . 66 ± 0.2 °, 24 . 59 ± 0.2 ° has a characteristic diffraction peak. The method of the invention by a water head preparation of spore zuozuo wo sodium compound, has good stability and meet the requirements as a raw material of a preparation. (by machine translation)
NOVEL INTERMEDIATES FOR SYNTHESIS OF CEPHALOSPORINS AND PROCESS FOR PREPARATION OF SUCH INTERMEDIATES
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Page 33, (2008/06/13)
A novel 4-halo-2-oxyimino-3-oxo butyric acid-N, N-dimethyl formiminium chloride chlorosulfate of formula (I) useful in the preparation of cephalosporin antibiotics, wherein X is chlorine or bromine; R is hydrogen, C1-4 alkyl group, an easily removable hydroxyl protective group, -CH2COOR5, or -C(CH3)2COOR5, wherein R5 is hydrogen or an easily hydrolysable ester group. The compound of formula (I) is prepared by reacting 4-halo-2-oxyimino-3-oxobutyric acid of formula (IV1), wherein X, R and R5 are as defined above, with N, N-dimethylformiminium chloride chlorosulphate of formula (VII), in an organic solvent at a temperature ranging from -30 °C to -15 °C. The cephalosporins that may be prepared from the intermediate include cefdinir, cefditoren pivoxil, cefepime, cefetamet pivoxil, cefixime, cefmenoxime, cefodizime, cefoselis, cefotaxime, cefpirome, cefpodoxime proxetil, cefquinome, ceftazidime, cefteram pivoxil, ceftiofur, ceftizoxime, ceftriaxone and cefuzonam.
7-[2-(2-Aminothiazol-4-yl)-2-cyclopentyloxyiminoacetamido]-3-cephem-4-carboxylic acid (synisomer)
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, (2008/06/13)
The invention relates to new thiadiazolyl or thiazolyl-substituted cephem and cepham compounds, the pharmaceutically acceptable salts and bioprecursors thereof, of antimicrobial activity, processes for preparation thereof, intermediates for preparing the new compounds and to pharmaceutical compositions comprising the new compounds, and methods of using the compositions for treatment of infectious diseases.
