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| | Cefprozil Basic information |
| Product Name: | Cefprozil | | Synonyms: | CEFPROZIL:(6R,7R)-7-[(2R)-2-AMINO-2-(4-HYDROXYPHENYL)ACETYLAMINO]-8-OXO-3-(1-PRO-PENYL)-5-THIA-1-AZABICYLO[4.2.0]OCT-2-ENE-2-CARBOXYLIC ACID;(6R,7R)-7-[[(2R)-2-Amino-2-(4-hydroxyphenyl)acetyl]amino]-8-oxo-3-(1-propen-1-yl)-5-Thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic Acid;Cefprozile;Cephprozyl;Procef;Prozef;5-Thia-1-azabicyclo4.2.0oct-2-ene-2-carboxylic acid, 7-(2R)-amino(4-hydroxyphenyl)acetylamino-8-oxo-3-(1-propenyl)-, (6R,7R)-;(6R,7R)-7-[(2R)-2-Amino-2-(4-hydroxyphenyl) acetylamino]-8-oxo-3-(1-pro-penyl)-5-thia-1-azabicylo [4.2.0]oct-2-ene-2-carboxylic acid | | CAS: | 92665-29-7 | | MF: | C18H19N3O5S | | MW: | 389.43 | | EINECS: | 618-870-0 | | Product Categories: | API;cephalosporins;Intermediates & Fine Chemicals;Aromatics;Heterocycles;Sulfur & Selenium Compounds;Pharmaceuticals | | Mol File: | 92665-29-7.mol |  |
| | Cefprozil Chemical Properties |
| Melting point | 215-217°C (dec.) | | Boiling point | 803℃ | | density | 1.53±0.1 g/cm3(Predicted) | | RTECS | XI0339000 | | Fp | >110°(230°F) | | storage temp. | Keep in dark place,Inert atmosphere,Store in freezer, under -20°C | | solubility | DMF: 0.3 mg/ml; DMSO: 2.5 mg/ml; PBS (pH 7.2): 1.25 mg/ml | | pka | 2.92±0.50(Predicted) | | form | Powder | | Water Solubility | Soluble in DMSO at 10mg/ml. Insoluble in water. | | BCS Class | 3 | | InChIKey | WDLWHQDACQUCJR-PBFPGSCMSA-N | | SMILES | N12[C@@]([H])([C@H](NC([C@H](N)C3=CC=C(O)C=C3)=O)C1=O)SCC(C=CC)=C2C(O)=O | | CAS DataBase Reference | 92665-29-7(CAS DataBase Reference) |
| | Cefprozil Usage And Synthesis |
| Description | Cefprozil is a new orally active cephalosporin useful in the treatment of otitis media,
uncomplicated skin and skin structure infections plus upper/lower respiratory tract
infections. Although structurally similar to cefadroxil, its spectrum of antibacterial
activity is comparable to cefaclor, but exhibits greater activity against S.aureus, S.
epidermidis, Listeria monocytogenes, Streptococci, H. influenzae, Propionibacterium
acnes. Clostridium perfringens and difficile. | | Chemical Properties | Pale Yellow Solid | | Originator | Bristol-Myers Squibb (U.S.A.) | | Uses | Semisynthetic oral cephalosporin consisting of approx. 90:10 Z/E isomeric mixture. Antibacterial | | Definition | ChEBI: A semisynthetic, second-generation cephalosporin, with prop-1-enyl and (R)-2-amino-2-(4-hydroxyphenyl)acetamido groups at positions 3 and 7, respectively, of the cephem skeleton. It is used to treat bronchitis as well as ear, skin and other bacterial infec
ions. | | Manufacturing Process | A mixture of 4-hydroxy-D-phenylglycine (10 g), ethylene glycol (15 ml) and
concentrated sulfuric acid (5 ml) was stirred for 18 hours at 55°C under
anhydrous conditions. The solution was cooled, and then ice (10 g) was added
to it, and the pH was adjusted to 1.0 with 10 N NH4OH (4.5 ml) giving 40 ml
of solution of hydroxyethyl ester of 4-hydroxy-D-phenylglycine.
The enzyme mixture of 20 ml containing immobilized recombinant penicillin G
amidase as the enzyme, 10% hydroxyethyl ester of 4-hydroxy-D-phenylglycine, 4% cefprozil (amine source), and 8% enzyme (immobilized
recombinant penicillin G amidase, equivalent to 32 IU/ml of enzyme) was
made up without buffer. The above prepared ester solution (6.9 ml) was
mixed with water (2 ml) and adjusted to pH 7.5 with 10 N NH4OH. Then the
amine source (0.8 g) was added to it and the pH adjusted to 7.5 with 1 N
NH4OH and the volume to 18.4 ml. Then the mixture was cooled to 5-15°C
and solid enzyme (1.6 g; 640 IU) was added to it. The pH was not maintained
at 7.5 and fell about 0.6 units during the reaction. The reaction mixture was
analyzed by HPLC on a C18 Reverse Phase column. The mobile phase was
10% acetonitrile/0.3% H3PO4. The isomers of cefprozil appeared at 2.9
minutes (cis) and at 5.1 minutes (trans). The final product was obtained with
a maximum yield of 92-96%. The whole experiment was completed in 25-50
min.
Synthesis of cefprozil may be carried out at 15°C using Boehringer penicillin G
amidase as the enzyme and hydroxyethyl ester of 4-hydroxy-D-phenylglycine.
A maximum yield of about 95%. The experiment was completed in 35
minutes. | | Brand name | Cefzil (Bristol-Myers Squibb). | | Therapeutic Function | Antibiotic | | Antimicrobial activity | Activity against Gram-positive cocci and Gram-negative
bacilli is better than that of cefadroxil (which it structurally
resembles) but is not as good as that of group 5 agents
. It is moderately stable to hydrolysis
by the common plasmid-mediated β-lactamases, but is hydrolyzed
by the chromosomal enzymes of Gram-negative bacilli
. | | Hazard | Moderately toxic by ingestion. Human sys-
temic effects.
| | Pharmacokinetics | Oral absorption: >90%
Cmax 250 mg oral: 5–7 mg/L after 1 h
500 mg oral: 10 mg/L after 1
Plasma half-life: 1–1.4 h
Volume of distribution: 15–201
Plasma protein binding: 35–45%
Absorption and distribution
It is almost completely absorbed and well distributed, penetrating
well into tonsillar and other tissues and inflammatory
exudate. Absorption is unaffected by food or
antacids and there is no accumulation on multiple dosing
regimens.
Metabolism and excretion
Most of the dose is excreted unchanged in urine, though
about 20% is found in feces. Urinary concentrations after a
500 mg oral dose usually exceed 1 g/L. The elimination halflife
is prolonged in patients with renal impairment, reaching
6 h in anuric patients. About half the drug is removed in 3 h
by hemodialysis. | | Pharmacokinetics | Oral absorption: >90%
Cmax 250 mg oral: 5–7 mg/L after 1 h
500 mg oral: 10 mg/L after 1
Plasma half-life: 1–1.4 h
Volume of distribution: 15–201
Plasma protein binding: 35–45%
Absorption and distribution
It is almost completely absorbed and well distributed, penetrating
well into tonsillar and other tissues and inflammatory
exudate. Absorption is unaffected by food or
antacids and there is no accumulation on multiple dosing
regimens.
Metabolism and excretion
Most of the dose is excreted unchanged in urine, though
about 20% is found in feces. Urinary concentrations after a
500 mg oral dose usually exceed 1 g/L. The elimination halflife
is prolonged in patients with renal impairment, reaching
6 h in anuric patients. About half the drug is removed in 3 h
by hemodialysis. | | Clinical Use | Cefprozil (Cefzil) is an orally active second-generationcephalosporin that is similar in structure and antibacterialspectrum to cefadroxil. Oral absorption is excellent (oralbioavailability is about 95%) and is not affected by antacidsor histamine H2-antagonists. Cefprozil exhibits greater invitro activity against streptococci, Neisseria spp., and S. aureusthan does cefadroxil. It is also more active than thefirst-generation cephalosporins against members of theEnterobacteriaceae family, such as E. coli, Klebsiella spp., P. mirabilis, and Citrobacter spp. The plasma half-life of1.2 to 1.4 hours permits twice-a-day dosing for the treatmentof most community-acquired respiratory and urinary tractinfections caused by susceptible organisms. | | Clinical Use | As for group 2 cephalosporins . It should not be used
in infections in which H. influenzae is, or is likely to be, implicated.
It should not be used as an alternative to penicillin in
syphilis. | | Clinical Use | It has been used for various infections for which oral cephalosporins
are appropriate. | | Side effects | It is well tolerated. Diarrhea and gastrointestinal discomfort
may occur. There have been a few reports of pseudomembranous
colitis and serum sickness-like reactions. | | Side effects | Nausea, vomiting and abdominal discomfort are relatively
common. Pseudomembranous colitis has been described and
overgrowth of Candida with vaginitis may be troublesome.
Otherwise, mild hypersensitivity reactions and biochemical
changes common to cephalosporins occur. Very rare neurological
disturbances have been described, particularly in patients
in whom very high plasma levels have been achieved. There
are rare reports of Stevens–Johnson syndrome and toxic epidermal
necrolysis. |
| | Cefprozil Preparation Products And Raw materials |
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