Cefuroxime

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Cefuroxime
Skeletal formula of cefuroxime
Ball-and-stick model of the cefuroxime molecule
Systematic (IUPAC) name
(6R,7R)-3-{[(aminocarbonyl)oxy]methyl}-7-{[(2Z)-2-(2-furyl)-2-(methoxyimino) acetyl]amino}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
Clinical data
Trade names Zinacef, Ceftin, TURBOCEF
MedlinePlus a601206
Pregnancy
category
  • B
Legal status
  • (Prescription only)
Routes of
administration
intramuscular, intravenous, oral
Pharmacokinetic data
Bioavailability 37% on an empty stomach, up to 52% if taken after food
Biological half-life 80 minutes
Excretion Urine 66–100% unchanged
Identifiers
CAS Registry Number 55268-75-2 YesY
ATC code J01DC02 S01AA27 QJ51DC02
PubChem CID: 5361202
DrugBank DB01112 YesY
ChemSpider 4514699 YesY
UNII O1R9FJ93ED YesY
KEGG D00262 YesY
ChEMBL CHEMBL466 YesY
Chemical data
Formula C16H16N4O8S
Molecular mass 424.386 g/mol
 YesY (what is this?)  (verify)

Cefuroxime or "Ceftin" is an enteral or oral second-generation cephalosporin antibiotic. Discovered by the Glaxo company (now GlaxoSmithKline), it was first marketed in 1978 as Zinacef and received approval from the U.S. Food and Drug Administration in October of 1983.[1]

Cefuroxime axetil is an acetoxyetyl-ester-prodrug of cefuroxime which is effective orally.[2]

Medical uses[edit]

As with the other cephalosporins, although as a second-generation variety, it is less susceptible to beta-lactamase. Hence, it may have greater activity against Haemophilus influenzae, Neisseria gonorrhoeae, and Lyme disease. Unlike most other second-generation cephalosporins, cefuroxime can cross the blood-brain barrier.

Side effects[edit]

Cefuroxime is generally well-tolerated and its side effects are usually transient. If ingested after food, this antibiotic is both better absorbed and less likely to cause its most common side effects of diarrhea, nausea, vomiting, headaches/migraines, dizziness, and abdominal pain compared to most antibiotics in its class.[citation needed]

Although a widely stated cross-allergic risk of about 10% exists between cephalosporins and penicillin, recent assessments have shown no increased risk for a cross-allergic reaction for cefuroxime and several other second-generation or later cephalosporins.[3]

Trade names[edit]

The U.S. patent for Cefuroxime has expired. It is sold generically there as Ceftin, and remains available as Zinacef by Covis Pharmaceuticals.[4] It is sold as Supacef by GSK in India,[5] and as Xorimax by Sandoz, Roxibac by RAK Pharmaceuticals Pvt. ltd., Turbocef by Beximco Pharmaceuticals and Furocef (ফিউরোসেফ) by Renata, Kilmax (কিলম্যাক্স)by SK+F Limited, Axet by Orion Pharma Ltd in Bangladesh.

Syntheses[edit]

The interposition of a syn-oximino ether moiety between the amide carbonyl and the aromatic ring has proven richly rewarding in that substantial resistance to Beta-lactamases results from this steric hinderance. A large number of analogues now bear this feature. The synthesis can be accomplished in a variety of ways.

2-acetylfuran is oxidized with nitrous acid to give 2-furyl(glyoxylic acid) (1), which is reacted with methoxylamine to give the corresponding oxime (2); this forms a mixed anhydride upon reaction with oxalyl chloride in DMF, and then reacted with the benzhydryl ester 7-aminocephalosporanic acid (7-ACA). The resulting product (3) undergoes enzymatic hydrolysis in an alkaline medium, in which the benzhydryl protection is not affected, and only the acetoxy group of the molecule at position C3 of the aminocephalosporanic acid is hydrolyzed. The resulting product with a free hydroxymethyl group (4) is reacted with chlorosulfonyl isocyanate, with intermediate formation of the corresponding N-chlorosulfonyl urethane (5), which is hydrolyzed by water to the urethane (6). Finally, removal of the benzyhydryl protection using trifluoroacetic acid gives the desired cefuroxime (7).

Another simpler way of the synthesis of cefuroxime is by direct acylation of 7-amino-3-aminocarbonyloxymethyl-3-cefem-4-carboxylic acid

Cefuroxime synthesis 3:[6] {citations from Lednicer book 3 were muddled}

Benzhydryl ester 1 (preparable from cephalothin is acylated with trichloroacetyl isocyanate and the side chain at C-7 is removed via the imino chloride method (pyridine and PCl5 followed by TsOH) to produce 7-aminocephalosporanic acid analogue 2. The carbamate moiety is partially hydrolyzed to give 3 through use of anhydrous methanolic hydrogen chloride (generated with methanol and acetyl chloride). Next, the benzhydryl ester is cleaved with trifluoroacetic acid and the synthesis concluded by a Schotten-Baumann reaction/acylation with the appropriate syn-oximinoether-bearing acid chloride so as to produce cefuroxime (6).

See also[edit]

References[edit]

  1. ^ "Cefuroxime medical facts from". Drugs.com. 
  2. ^ Walter Sneader. "Drug Discovery: History". 
  3. ^ Pichichero ME (2006). "Cephalosporins can be prescribed safely for penicillin-allergic patients" (PDF). The Journal of family practice 55 (2): 106–12. PMID 16451776. 
  4. ^ http://www.covispharma.ch/assets/pdf/covis-pharma-acquires-portfolio-of-drugs-from-glaxosmithkline.pdf
  5. ^ "GlaxoSmithKline Pharmaceuticals.Prescription Medicines – Anti-Infective". Gsk-india.com. 26 March 2013. 
  6. ^ M. C. Cook, G. I. Gregory, and J. Bradshaw, DE 2439880  (1975); Chem. Abstr., 83, 43354z (1975).