35607-66-0 Usage
Description
Cefoxitin contains the same C-7 side chain as cephalothin and the same C-3 side chain as cefuroxime. The
most novel chemical feature of cefoxitin is the possession of an α-oriented methoxyl group in place of the
normal H-atom at C-7. This increased steric bulk conveys very significant stability against β-lactamases. The
inspiration for these functional groups was provided by the discovery of the naturally occurring antibiotic
cephamycin C
derived from fermentation of Streptomyces lactamdurans. Cephamycin C itself has not seen clinical use but,
rather, has provided the structural clue that led to useful agents such as cefoxitin. Agents that contain this
7α methoxy group are commonly referred to as cephamycins. Ingenious chemical transformations now enable
synthetic introduction of such a methoxy group into cephalosporins lacking this feature.
Uses
Different sources of media describe the Uses of 35607-66-0 differently. You can refer to the following data:
1. Cefoxitin?is a semisynthetic, broad-spectrum second-generation cephalosporin with antibacterial activity. The activity of cefoxitin results in the weakening of the bacterial cell wall and causes cell lysis. Cefoxitin acts by interfering with cell wall synthesis. Its activity spectrum includes a broad range of gram-negative and gram-positive bacteria including anaerobes.
2. Antibacterial.
Therapeutic Function
Antibiotic
Antimicrobial activity
Most Gram-positive bacilli are susceptible, but L. monocytogenes is resistant. It is resistant to many Gramnegative
β-lactamases and is active against organisms elaborating
them, including some Citrobacter, Providencia, Serratia
and Acinetobacter spp. Enterobacter spp. are resistant. It is moderately
active against Bacteroides spp., but considerable strain
variation in susceptibility occurs.
Acquired resistance
Resistant strains of Bacteroides, some of which produce
β-lactamases that hydrolyze cefoxitin, have been described.
Resistance may be transferable to other Bacteroides spp. It is a
potent inducer of chromosomal cephalosporinases of certain
Gram-negative bacilli and can antagonize the effect
of cefotaxime and other β-lactam agents.
Pharmacokinetics
Cmax 500 mg intramuscular: 11 mg/L after 20 min
1 g intravenous: c. 150 mg/L end injection
Plasma half-life: 0.7–1 h
Volume of distribution: c. 10 L
Plasma protein binding: 65–80%
Absorption
It is not absorbed when given orally, but is very rapidly
absorbed from intramuscular sites. Doubling the dose approximately
doubles the plasma level. It is absorbed from suppositories
to varying degrees depending on the adjuvants: peak
serum levels around 9.8 mg/L have been obtained after a dose
of 1 g, giving a bioavailability of around 20%. In infants and
children treated with 150 mg/kg per day, mean serum concentrations
15 min after intravenous and intramuscular administration
were 81.9 and 68.5 mg/L, with elimination half-lives
of 0.70 and 0.67 h, respectively.
Distribution
About 20% of the corresponding serum levels are found in
sputum. In patients given 1 g by intravenous bolus preoperatively,
concentrations in lung tissue at 1 h were around 13 mg/g.
Penetration into normal CSF is very poor; even in patients
with purulent meningitis CSF concentrations seldom exceed
6 mg/L. In children with meningitis receiving 75 mg/kg every
6 h, peak concentrations of 5–6 mg/L were found around 1 h
after the dose. In patients receiving 2 g intravenously before
surgery, the mean penetrance into peritoneal fluid was 86%.
In patients receiving 2 g intramuscularly before hysterectomy,
mean concentrations in pelvic tissue were 7.8 mg/g.
Breast milk contained 5–6 mg/L after a 1 g intravenous dose.
Concentrations up to 230 mg/L have been found in bile after
2 g intravenously.
Metabolism and excretion
Less than 5% of the drug is desacetylated and in a few subjects
deacylation of 1 or 2% of the dose to the antibacterially
inactive descarbamyl form also occurs.
It is almost entirely excreted in the urine by both glomerular
filtration and tubular secretion, 80–90% being found
in the first 12 h after a parenteral dose, producing concentrations
in excess of 1 g/L. Furosemide, in doses of 40–160 mg,
had no effect on the elimination half-life of doses of 1 or 2 g.
Probenecid delays the plasma peak and decreases the renal
clearance and urine concentration. The renal clearance has
been calculated variously to lie between 225 and 330 mL/
min. The plasma half-life increases inversely with creatinine
clearance to reach 24 h in oliguric patients, with corresponding
reduction in total body clearance. In patients on peritoneal
dialysis, peritoneal clearance accounted for only 7.5% of
mean plasma clearance and the mean plasma half-life during
6 h dialysis was 7.8h.
Clinical Use
As for other group 3 cephalosporins, with particular emphasis
on mixed infections including anaerobes, notably abdominal
and pelvic sepsis. In considering its use, its low activity against
aerobic Gram-positive cocci should be noted.
Side effects
Reactions are those common to cephalosporins. Pain on
intramuscular, and thrombophlebitis on intravenous, injection
occur. Substantial changes can occur in the fecal flora,
with virtual eradication of susceptible enterobacteria and
non-
fragilis Bacteroides, and appearance of, or increase in,
yeasts, enterococci and other resistant bacteria including
C. difficile. Development of meningitis due to H. influenzae and
Str. pneumoniae in patients treated for other infections has been
observed.
Synthesis
Cefoxitin, 3-(hydroxymethyl)-8-oxo-7-methoxy-7-[(2-thienylacetyl)amino]-
5-thia-1-azabicyclo[4.2.0]oct-2-en-2-carboxylic acid carbamate (32.1.2.30), is synthesized
in various ways starting from cefamicin C-7β-(D-5-amino-5-carboxyvaleramido)-
3-aminocarbonylhydroxymethyl-7-methoxy-3-cefem-4-carboxylic acid, in which a
methoxy group is initially present at C7, and the task of making the desired drug essentially
consists of a transamidation reaction.The other way is to start synthesis from 7-aminocephalosporanic acid, to which it is necessary to insert a methoxy group at C7. In one of the examples of the synthesis of cefoxitin starting from cefamicin C, the free amino group is initially protected via tosylation,
and the product in the form of a well-crystallizing dicyclohexylamine salt is isolated
(32.1.2.28). Next, the carbonyl group at position 2 of the cephalosporanic system is esterified using methylchloromethyl ether. The resulting compound (32.1.2.29) is reacted with
2-(2-thienyl)acetylchloride, then the ester protection is removed from the carboxylic group
with hydrogen chloride in methanol, producing the desired cefoxitin (32.1.2.30).Another way for the synthesis of cefoxitin is started from 7-aminocephalosporanic acid,
more correct, from its benzhydryl ester (32.1.2.31), which is synthesized by previous
tosylation of the amino group of the initial 7-aminocephalosporanic acid, esterification of
the carboxyl group by diphenyldiazomethane, and subsequent removal of the tosyl protection.When reacted with nitrous acid, the product is diazotized, giving the diphenyl methyl
ester of 7-diazocephalosporanic acid (32.1.2.32). A subsequent reaction of the resulting
compound with triethylammonium azide in dichloromethane and then with bromine azide
gives the diphenyl methyl ester of 7-bromo-7-azidocephalosporanic acid (32.1.2.33).
Treating this with methanol in the presence of silver borofluoride results in the replacement
of the bromine atom, giving the diphenylmethyl ester of 7-methoxy-7-azidocephalosporanic
acid (32.1.2.34). The resulting azide is reduced by hydrogen in the presence of a platinum oxide catalyst, forming the diphenyl methyl ester of 7-methoxy-7-aminocephalosporanic
acid (32.1.2.35). Acylation of this compound with 2-(2-thienyl)acetylchloride gives the benzhydryl ester of 7-methoxy-7-[2-(2-thienyl)-acetamido]cephalosporanic acid (32.1.2.36),
the ester protecting group of which is hydrolyzed using trifluoroacetic acid and then upon
reacting the resulting acid with sodium bicarbonate, it is transformed to the potassium salt
(32.1.2.37). The resulting product is then hydrolyzed by the enzyme Citrusi acetylesterase
to the potassium salt of 3-hydroxymethyl-7-methoxy-7-[2-(2-thienyl)acetamido]-3-cefem-
4-carboxylic acid (32.1.2.38). Using the method described above, i.e. the initial reaction
with chlorosulfonyl isocyanate followed by hydrolysis with water, the resulting compound,
(32.1.2.38), is transformed to the desired cefoxitin (32.1.2.20).
Check Digit Verification of cas no
The CAS Registry Mumber 35607-66-0 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 3,5,6,0 and 7 respectively; the second part has 2 digits, 6 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 35607-66:
(7*3)+(6*5)+(5*6)+(4*0)+(3*7)+(2*6)+(1*6)=120
120 % 10 = 0
So 35607-66-0 is a valid CAS Registry Number.
InChI:InChI=1/C16H17N3O7S2/c1-25-16(18-10(20)5-9-3-2-4-27-9)13(23)19-11(12(21)22)8(6-26-15(17)24)7-28-14(16)19/h2-4,14H,5-7H2,1H3,(H2,17,24)(H,18,20)(H,21,22)/t14?,16-/m0/s1
35607-66-0Relevant articles and documents
Preparation method of cefoxitin
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Paragraph 0017-0036, (2020/06/17)
The invention relates to a preparation method of cefoxitin. The method comprises the following steps of: adding dichloromethane into a raw material aqueous solution, then adding an N, N'-dibenzyl ethylenediamine diacetate aqueous solution, performing filtration to obtain an intermediate 1, and adding the intermediate 1 into dichloromethane, adding chlorosulfonyl isocyanate to react, carrying out acidolysis at the end of the reaction, adding sodium bicarbonate to adjust the pH value to 8, adding a methanol solution of sodium methoxide, adding sodium bicarbonate at the end of the reaction to adjust the pH value to 8, subjecting water-phase activated carbon to decolorization, then adding acid to adjust the pH value to 4, performing crystallizing, and conducting filtering and drying to obtaincefoxitin. According to the method, the intermediate is always salified, condensation side reactions are avoided, intermediate treatment is reduced, and the product yield and purity are well controlled.
Synthesis method of cefoxitin sodium
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, (2019/05/08)
The invention provides a synthesis method of cefoxitin sodium. The synthesis method is characterized in that cefalotin acid is taken as the raw material to sequentially synthesize 7-a-methoxyl cefalotin cyclohexane salt, 7-a-methoxyl-3-deacetyl cefalotin benzathine salt, and cefoxitin acid to obtain the target product; cefalotin acid reacts with tert.-butyl hypochloric acid to obtain 7-a-methoxylcefalotin cyclohexane salt, and after reactions, the reaction product is purified by a post treatment. The provided synthesis method can largely reduce the happening rate of side reactions, hydrolysis, and degradation, reduces the impurities, improves the product quality, and increases the yield. Moreover, the product quality is stable, the operation is simple, and the synthesis method is suitablefor industrial production.
A head cefoxitin acid synthesis technology
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, (2017/04/21)
The invention provides a novel synthesis method of cefoxitin acid. Cefoxitin acid is used as a raw material for synthesizing cefoxitin sodium and belongs to second-generation cephalosporin. The cefoxitin acid has balanced antibacterial spectra and has a strong antibacterial effect on gram-negative bacteria. Due to the existence of 7alpha methoxy in the cefoxitin acid, the hydrolysis action of the cefoxitin acid on beta-lactamase can be reduced greatly, so that the beta-lactamase can exist stably in the cefoxitin acid. In the invention, 3-deacetylase cefoxitin acid which is an intermediate is produced by adopting an enzyme process through two-step continuous reaction, materials react in a mild reaction condition, and the process is simple and is convenient to operate. By adopting the novel synthesis method, time and labor can be saved, and the yield and quality of the product can be improved. Because the two-step reaction is carried out in a water phase at room temperature, the consumption of energy and the discharge of organic wastewater can be reduced greatly. The novel synthesis method meets the requirements of large-scale industrial production.
