62893-19-0 Usage
Description
Cefoperazone is a semi-synthetic parenteral cephalosporin antibiotic with a tetrazolyl moiety that confers beta-lactamase resistance. It is characterized by its white crystalline appearance and has a C-7 side chain similar to piperacillin and a C-3 side chain (MTT) that is associated with bleeding and alcohol intolerance issues in patients taking cephalosporins. Its useful activity against pseudomonads partly compensates for its limitations, although it is not potent enough to be used as a single agent against this pathogen. The C-7 side chain does not provide sufficient resistance to many beta-lactamases, but the addition of clavulanic acid or sulbactam could potentially enhance its effectiveness.
Uses
Used in Antibacterial Applications:
Cefoperazone is used as an antimicrobial agent for treating bacterial infections of various types. Its broad spectrum of antimicrobial action includes most clinically significant microorganisms, such as Gram-positive, Gram-negative, aerobic, and anaerobic bacteria. It is stable with respect to most beta-lactamases of Gram-positive and Gram-negative bacteria.
Cefoperazone is used as an antimicrobial agent for bacterial infections in the following areas:
1. Lower respiratory tract infections
2. Urinary and sexual tract infections
3. Bone and joint infections
4. Skin and soft tissue infections
5. Abdominal and gynecological infections
Used as a β-lactamase Inhibitor:
Cefoperazone acid is used as an antimicrobial β-lactamase inhibitor, which helps to enhance the effectiveness of other antibiotics by preventing their degradation by bacterial enzymes.
Synonyms and Brand Names:
Cefoperazone is also known by various synonyms, including cefazon, cefobid, cefobis, and many others. One of its brand names is Cefobid, which is manufactured by Pfizer.
Originator
Cefobid,Pfizer,W. Germany,1981
Manufacturing Process
To a suspension of 3.0 g of 7-[D-(-)-α-amino-p-hydroxyphenylacetamido]-3-
[5-(1-methyl-1,2,3,4-tetrazolyl)thiomethyl]-?3-cephem-4-carboxylic acid in 29
ml of water was added 0.95 g of anhydrous potassium carbonate. After the
solution was formed, 15 ml of ethyl acetate was added to the solution, and
1.35 g of 4-ethyl-2,3-dioxo-1-piperazinocarbonyl chloride was added to the
resulting solution at 0°C to 5°C over a period of 15 minutes, and then the
mixture was reacted at 0°C to 5°C for 30 minutes. After the reaction, an
aqueous layer was separated off, 40 ml of ethyl acetate and 10 ml of acetone were added to the aqueous layer, and then the resulting solution was adjusted
to a pH of 2.0 by addition of dilute hydrochloric acid. Thereafter, an organic
layer was separated off, the organic layer was washed two times with 10 ml of
water, dried over anhydrous magnesium sulfate, and the solvent was removed
by distillation under reduced pressure. The residue was dissolved in 10 ml of
acetone, and 60 ml of 2-propanol was added to the solution to deposit
crystals. The deposited crystals were collected by filtration, washed with 2-
propanol, and then dried to obtain 3.27 g of 7-[D-(-)-α-(4-ethyl-2,3-dioxo)-1-
piperazinocarbonylamino)-p-hydroxyphenylacetamido]-3-[5-(1-methyl-
1,2,3,4-tetrazolyl)thiomethyl]-?3-cephem-4-carboxylicacid, yield 80.7%. The
product forms crystals, MP 188°C to 190°C (with decomposition).
Therapeutic Function
Antibiotic
Antimicrobial activity
A semisynthetic parenteral cephalosporin. It is unstable, losing
activity on storage even at –20°C. A formulation with sulbactam
is available in some countries.
It exhibits moderate activity against carbenicillin-sensitive
strains of Ps. aeruginosa. Activity against Burk. cepacia and
Sten. maltophilia is unreliable. It is much less stable to enterobacterial
β-lactamases than most other cephalosporins of
groups 4–6 and consequently has unreliable activity against
many species, including β-lactamase-producing strains of
H. influenzae
and N. gonorrhoeae. It is active against
Achromobacter, Flavobacterium, Aeromonas and associated
non-fermenters. Past. multocida is extremely susceptible (MIC
<0.01–0.02 mg/L). It exhibits modest activity against most
Gram-negative anaerobes, but not B. fragilis. Sulbactam
increases activity against many, but not all, enterobacteria and
non-fermenters, and almost all B. fragilis.
A 2 g intravenous infusion achieves a peak plasma concentration
of 250 mg/L. The plasma half-life is 1.5–2 h. Over
85% is bound to plasma proteins. It achieves therapeutic concentrations
in tissue and inflammatory exudates. Variable low
levels are found in the sputum up to 1.5% of simultaneous
serum levels. Penetration into CSF is unreliable even in the
presence of meningeal inflammation.
The bile is a major route of excretion, accounting for
almost 20% of the dose. About 20–30% is eliminated in urine,
almost entirely by glomerular filtration. Clearance is effectively
unchanged by renal failure or dialysis.
Side effects associated with the methylthiotetrazole side
chain have been reported. Diarrhea has been notable in some
studies. Marked suppression of fecal flora, with the appearance
of C. difficile, has occasionally been found. There is a 5–10%
incidence of mild transient increases in liver function tests.
Its potential toxicity and the availability of compounds
with better β-lactamase stability and more reliable antipseudomonal
activity have undermined its popularity.
Synthesis
Cefoperazone, (6R,7R)-7-[(R)-2-(4-ethyl-2,3-dioxo-1-piperazincarboxamido)-2-(p-hydroxyphenyl)acetamido]-3-[[(1-methyl-1H-tetrazol-5-yl)thio]methyl]-8-oxo-
5-thia-1-azabicyclo[4.2.0]oct-2-en-2-carboxylic acid (32.1.2.84), is synthesized by acylating
7-amino-3-(1-methyl-1,2,3,4-tetrazol-5-yl)-thiomethyl-3-cefem-4-carboxylic acid (32.1.2.24)
with a mixed anhydride synthesized from ethyl chloroformate and α-(4-ethylpiperazin-2,
3-dion-1-carbonylamino)-4-hydroxyphenylacetic acid (32.1.2.83), which in turn is synthesized from 4-ethylpiperazin-2,3-dion-1-carboxylic acid (32.1.1.29) and the sodium salt of
4-hydroxyphenylglycine.
references
[1]. kato y1,takahara s,kato s,kubo y,sai y,tamai i,yabuuchi h,tsuji a. involvement of multidrug resistance-associated protein 2 (abcc2) in molecular weight-dependent biliary excretion of beta-lactam antibiotics.drug metab dispos.2008 jun;36(6):1088-96. doi: 10.1124/dmd.107.019125. epub 2008 mar 13.[2]. craig wa,gerber au. pharmacokinetics of cefoperazone: a review. drugs.1981;22suppl 1:35-45.
Check Digit Verification of cas no
The CAS Registry Mumber 62893-19-0 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 6,2,8,9 and 3 respectively; the second part has 2 digits, 1 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 62893-19:
(7*6)+(6*2)+(5*8)+(4*9)+(3*3)+(2*1)+(1*9)=150
150 % 10 = 0
So 62893-19-0 is a valid CAS Registry Number.
InChI:InChI=1/C25H27N9O8S2/c1-3-32-8-9-33(21(39)20(32)38)24(42)27-15(12-4-6-14(35)7-5-12)18(36)26-16-19(37)34-17(23(40)41)13(10-43-22(16)34)11-44-25-28-29-30-31(25)2/h4-7,15-16,22,35H,3,8-11H2,1-2H3,(H,26,36)(H,27,42)(H,40,41)/t15-,16+,22+/m0/s1
62893-19-0Relevant articles and documents
New adaptation diseases of cefoperazone medicinal preparation for treating endometritis and other gynecological genital tract infections
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Paragraph 0108; 0110-0111, (2020/08/22)
The invention discloses new adaptation diseases of cefoperazone medicinal preparation for treating gynecological genital tract infections of gynecology department. The cefoperazone sodium provided bya specific raw material production process is extremely low in impurity content and remarkable in medicine effect, so that the quality of a preparation product is improved, the safety and effectiveness of the preparation product are guaranteed, and the invention provides the application of preparing the medicine for treating endometritis and other gynecological genital tract infections.
Synthetic method of cefoperazone acid
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, (2016/11/17)
The invention discloses a synthetic method of cefoperazone acid. The method comprises the steps of: reacting raw materials of 7-ACA and 1-methyl-5-mercapto tetrazole under the catalysis of boron trifluoride acetonitrile to obtain 7-ACT; dissolving the 7-ACT in a mixed solution of acetonitrile and N,O-(bis) trimethylsilyl acetamide to obtain a 7-ACT amino alkylate solution; mixing HO-EPCP, an organic solvent and a catalyst, adding phosphorus oxychloride for reaction at the temperature of -25 to -20 DEG C, wherein when the residue amount of HO-EPCP in the reaction solution is no more than 0.5%, the reaction is complete, so as to prepare a HO-EPCP acyl chloride solution; mixing and reacting 7-ACT amino alkylate solution with HO-EPCP acyl chloride solution, adding an aqueous solution of sodium bicarbonate after the reaction, standing foe stratification, filtering a lower layer material, adding water, crystallizing, filtering, washing and drying to obtain the cefoperazone acid. The method has the advantages of simpleness, high yield and stable intermediate.
NOVEL CRYSTALLINE CEFOPERAZONE INTERMEDIATE
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Paragraph 0063, (2015/04/28)
The present invention relates to a crystalline form of an intermediate for cefoperazone of formula (1) and to a process for the preparation thereof by enzymatic condensation of a 3′-thiosubstituted β-lactam nucleus with a phenylglycine derivative.
