53994-73-3 Usage
Description
Cefaclor is a cephalosporin antibiotic that is active against various bacteria, including S. pyogenes, S. pneumoniae, S. aureus, P. mirabilis, S. typhi, E. coli, and H. influenzae. It is characterized by its white crystalline solid appearance and is known for its acid stability, allowing for oral administration. Cefaclor is less active against Gram-negative bacteria compared to other second-generation cephalosporins but is more active against them than first-generation drugs. It is available under the brand names Ceclor (Lilly) and Raniclor (Ranbaxy).
Uses
Used in Pharmaceutical Industry:
Cefaclor is used as an antibiotic for the treatment of various bacterial infections, such as urinary tract, intra-abdominal, and Haemophilus influenzae infections. It is effective against a range of bacteria, including S. pyogenes, S. pneumoniae, S. aureus, P. mirabilis, S. typhi, E. coli, and H. influenzae.
Used in Medical Research:
Cefaclor is used to study the mechanism of human renal organic anion and peptide transporters, such as hOAT1, hPEPT1, and hPEPT2. It is also used to study the effects of inhibition of penicillin-binding proteins on bacterial cell wall mucopeptide synthesis.
Used in Treatment of Septicaemia, Pneumonia, Meningitis, Biliary-Tract Infections, Peritonitis:
Cefaclor, as a member of the cephalosporins family, is a broad-spectrum antibiotic used for the treatment of various severe bacterial infections, including septicaemia, pneumonia, meningitis, biliary-tract infections, and peritonitis.
Originator
Ceclor,Lilly,US,1979
Manufacturing Process
Preparation of 7-amino-3-chloro-3-cephem-4-carboxylic acid: To a solution of
750 mg (185 mmol) of p-nitrobenzyl 7amino-3-chloro-3cephem-4-carboxylate
hydrochloride in 20 ml of tetrahydrofuran and 40 ml of methanol was added a
suspension of 750 mg of prereduced 5% palladium on carbon catalyst in 20
ml of ethanol and the suspension was hydrogenated under 50 psi of hydrogen
at room temperature for 45 minutes. The catalyst was filtered and washed
with THF and water. The filtrate and catalyst washes were combined and
evaporated to dryness, The residue was dissolved in a water-ethyl acetate
mixture and the pH adjusted to pH 3. The insoluble product was filtered and
triturated with acetone. The product was then dried to yield 115 mg of 7-
amino-3-chloro-3-cephem-4-carboxylic acid.Preparation of 7-(D-α-phenylglycylamido)-3-chloro-3-cephem-4-carboxylic
acid: To a suspension of 280 mg (1.2 mmol) of 7-amino-3-chloro-3-cephem-
4-carboxylic acid in 14 ml of acetonitrile was added with stirring at room
temperature 0.5 ml of N,O-bis-(trimethylsilyl)acetamide to form the soluble
disilylmethyl derivative thereof. The solution was cooled to 0 C and was slowly
added to a solution of the mixed anhydride formed by reacting 408 mg (1.5
mmol) of methyl-3-α-carboxybenzylaminocrotonate sodium salt with 161 mg
(1.7 mmol) of methyl chloroformate in the presence to 2 drops of N,N-dimethylbenzyl amine in 7 ml of acetonitrile.The mixture was stirred at ice bath temperature for 2 hours, 1 ml of methanol
was added and the mixture was filtered to remove insoluble impurities. Two
milliliters of water were added to the filtrate and the pH was adjusted
momentarily to pH 1.5, to effect removal of the enamine block, and then to
pH 4.5 with triethylamine. After stirring for an additional hour at ice bath
temperature the reaction product, 7-(D-α-phenylglycylamido)-3-chloro-3-
cephem-4-carboxylic acid (zwitterion) precipitated from the reaction mixture
as a crystalline solid. The product was filtered, washed with acetonitrile and
dried in vacuo to yield 200 mg.
Therapeutic Function
Antibiotic
Antimicrobial activity
It is less resistant than other group 2 cephalosporins
to staphylococcal β-lactamase. It is active against
N. gonorrhoeae and H. influenzae and against most enterobacteria,
but it is susceptible to common enterobacterial
β-lactamases. Pr. vulgaris and Providencia, Acinetobacter and
Serratia spp. are resistant. B. fragilis and clostridia are resistant
but other anaerobes are commonly susceptible.
Pharmacokinetics
Oral absorption: c. 90%
Cmax 250 mg oral: c. 6–7 mg/L after 50 min
Plasma half-life: 0.5–1 h
Volume of distribution: 0.37 L
Plasma protein binding: 25%
Absorption
Food intake increases the time taken to reach peak plasma
levels and reduces the peak by 25–50%. The actual amount
absorbed is unaffected. In children receiving 15 mg/kg per
day (maximum daily dose 1 g) the mean peak serum level was
16.8 mg/L at 0.5–1 h. There is no accumulation of the drug
during repeated administration.
Distribution
In patients receiving 500 mg every 8 h for 10 days, concentrations
were 0–1.7 (mean 0.5) mg/L in mucoid sputum and
0–2.8 (mean 1.0) mg/L in purulent sputum. In children with
chronic serous otitis media receiving 15 mg/kg per day, the
mean peak concentration in middle ear secretion was 3.8 mg/L
within 30 min of the dose when the mean simultaneous serum
concentration was 12.8 mg/L. Metabolism and excretion
No metabolites have been identified, but the drug probably
chemically degrades in serum. About half of the dose is recovered
from the urine in the first 6 h and 70% in 24 h. Probenecid
prolongs the plasma levels but in renal insufficiency the plasma
half-life is only moderately increased. In patients with creatinine
clearance values of 5–15 mL/min the mean plasma elimination
half-life rose to 2.3 h and the 24 h urinary excretion fell to less than 10%. In patients requiring intermittent hemodialysis
and receiving 500 mg every 8 h for 10 days, the half-life rose
to 2.9 h. Dialysis removed 34% of the dose
Clinical Use
Cefaclor (Ceclor) is an orally active semisyntheticcephalosporin that was introduced in the American market in1979. It differs structurally from cephalexin in that the 3-methyl group has been replaced by a chlorine atom. It issynthesized from the corresponding 3-methylenecepham sulfoxideester by ozonolysis, followed by halogenation of theresulting β-ketoester. The 3-methylenecepham sulfoxideesters are prepared by rearrangement of the corresponding 6-acylaminopenicillanic acid derivative. Cefaclor is moderatelystable in acid and achieves enough oral absorption to provideeffective plasma levels (equal to about two-thirds of thoseobtained with cephalexin). The compound is apparentlyunstable in solution, since about 50% of its antimicrobial activityis lost in 2 hours in serum at 37°C. The antibacterialspectrum of activity is similar to that of cephalexin, but it isclaimed to be more potent against some species sensitiveto both agents. Currently, the drug is recommended for thetreatment of non–life-threatening infections caused by H.influenzae, particularly strains resistant to ampicillin.
Clinical Use
Uses are similar to those of other group 2 cephalosporins.
It is among the few suitable for use in respiratory infections
because of its activity against H. influenzae.
Side effects
Apart from mild gastrointestinal disturbance, the drug is
well tolerated. Transiently increased transaminase levels and
symptomatic vaginal candidosis have been noted. Clusters of
a serum sickness-like illness have been described in children.
Safety Profile
Moderately toxic by intraperitoneal route. Human systemic effects by ingestion: joints, dermatitis, increased body temperature. An experimental teratogen. Experimental reproductive effects. When heated to decomposition it emits toxic fumes of Clí, SOx, an
Synthesis
Cefaclor, (6R,7R)-7-[(R)-2-amino-2-phenylacetamido]-3-chloro-8-oxo-5-thia-
1-azabicyclo[4.2.0]oct-2-en-2-carboxylic acid (32.1.2.48), is synthesized from the most accessible antibiotic of
this series, cefalotin (32.1.2.1), in which the carboxyl group is protected by esterification by
a reaction with 4-nitrobenzylbromide in triethylamine, giving the 4-nitrobenzyl ester of
7-(2-thienylacetamido)-cephalosporanic acid (32.1.2.40). Reacting this with potassium
ethyl xantogenate replaces the acetoxy group in the third position of the cephalosporin system, giving the corresponding S-derivative (32.1.2.41). Upon reducing this compound using
zinc in formic acid, the product is desulfurized, giving the 4-nitrobenzyl ester of
3-exo-methylen-7-(2-thienylacetamido)-cefem-4-carboxylic acid (32.1.2.42). The exomethylene group is oxidized by ozone and the resulting dicarbonyl derivative tautomerizes
to the enol form (32.1.2.43) upon reaction with sulfur anhydride. Then, the hydroxyl group
is replaced with a chlorine atom upon reaction with thionyl chloride, giving the 4-nitrobenzyl ester of 3-chloro-7-(2-thienylacetamido)-3-cefem-4-carboxylic acid (32.1.2.44). The
resulting product undergoes deacylation upon reaction with a mixture of pyridine with
phosphorous pentachloride in isobutanol, forming the hydrochloride of 4-nitrobenzyl ester
of 7-amino-3-chloro-3-cefem-4-carboxylic acid (32.1.2.45). This is acylated with an
N-protected derivative of phenylglycine, (N-tert-butoxycarbonyl)-D-α-phenylglycine in the
presence of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline in tetrahydrofuran, giving the product (32.1.2.46). The tert-butoxycarbonyl protection in this molecule is removed by
heating in acetonitrile in the presence of p-toluenesulfonic acid. Finally, upon hydrogen
reduction using zinc and hydrochloric acid in dimethylformamide, the 4-nitrobenzyl protecting group is removed from the resulting tosylate (32.1.2.47) giving cefaclor (32.1.2.48).
Veterinary Drugs and Treatments
Cefaclor may potentially be useful when an oral cephalosporin is
desired to treat infections that are susceptible to it but resistant to
first generation cephalosporins such as cephalexin or cefadroxil.
Little information is available with regard to its clinical use in small
animals, however.
Drug interactions
Potentially hazardous interactions with other drugs
Anticoagulants: effects of coumarins may be
enhanced.
Metabolism
Cefaclor is rapidly excreted by the kidneys; up to 85% of
a dose appears unchanged in the urine within 8 hours, the
greater part within 2 hours. Probenecid delays excretion
Check Digit Verification of cas no
The CAS Registry Mumber 53994-73-3 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 5,3,9,9 and 4 respectively; the second part has 2 digits, 7 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 53994-73:
(7*5)+(6*3)+(5*9)+(4*9)+(3*4)+(2*7)+(1*3)=163
163 % 10 = 3
So 53994-73-3 is a valid CAS Registry Number.
InChI:InChI=1/C16H16ClN3O4S/c1-16-12(19-13(21)10(18)8-5-3-2-4-6-8)14(22)20(16)11(15(23)24)9(17)7-25-16/h2-6,10,12H,7,18H2,1H3,(H,19,21)(H,23,24)/t10-,12-,16+/m1/s1
53994-73-3Relevant articles and documents
Cefaclor preparation and preparation method thereof
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Paragraph 0033; 0088; 0089, (2017/04/29)
The invention discloses a cefaclor preparation and a preparation method thereof. The preparation method comprises: preparing cefaclor crystal, pretreating a main material and auxiliary materials, weighing, mixing, forming, and packaging; wherein the preparation of the cefaclor crystal includes subjecting 7-ACCA and potassium (R)-[(3-ethoxy-1-methyl-3-oxoprop-1-enyl)amino]phenylacetate to silylation, acylation, condensation, acid hydrolysis, extraction and cleaning, decoloring, and crystallization; the preparation comprises the cefaclor crystal as the main material and auxiliary materials, the cefaclor crystal is /=33 degrees in angle of repose, 0.50-0.60 g/m in bulk density, 0.70-0.80 g/ml in compactness and 40-60 Mum in D10 of particle size distribution, 120-140 Mum in D50 and 210-230 Mum in D90. The conversion rate of cefaclor in chemical synthesis is increased, reaction conditions are simplified, the crystal form and particle size distribution of the cefaclor crystal are improved, and the quality of finished cefaclor crystal is improved.
Process for the preparation of 3-chloro-cefem compounds
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, (2008/06/13)
The process comprises a series of stages essentially comprising the protection of the functional groups of the side chain of Ampicillin, esterification of the acid group, oxidation to sulphoxide, expansion of the thiazole ring to a thiazine ring, ozonolysis of the exomethylene cefam derivative obtained, substitution of the hydroxyl group by chlorine and de-protection of the functional groups, in which the order of some stages can be varied without affecting the final result.