66592-87-8

Basic information

• Product Name: Cefadroxil
• Synonyms: (6R,7R)-7-[(R)-2-AMINO-2-(4-HYDROXY-PHENYL)-ACETYLAMINO]-3-METHYL-8-OXO-5-THIA-1-AZA-BICYCLO[4.2.0]OCT-2-ENE-2-CARBOXYLIC ACID;CEFAMOX;CEFADROXIL;CEFADROXIL MONOHYDRATE;P-HYDROXYCEPHALEXINE;monohydrate,(6r-(6-alpha,7-beta(r*)))-l)acetyl)amino)-3-methyl-8-oxo;Cefradroxil;(6R,7R)-7-[[(2R)-Amino-(4-hydroxyphenyl)acetyl]amino]-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic Acid Monohydrate
• CAS NO: 66592-87-8
• Molecular Formula: C₁₆H₁₇N₃O₅S*H₂O
• Molecular Weight: 381.41
• EINECS: 1308068-626-2
• Product Categories: Intermediates & Fine Chemicals;Pharmaceuticals;Sulfur & Selenium Compounds;DURICEF
• Mol File: 66592-87-8.mol

Chemical Properties

• Melting Point: 197 °C
• Boiling Point: 789.9 °C at 760 mmHg
• Flash Point: 431.5 °C
• Appearance: White crystalline solid
• Vapor Pressure: 2.71E-26mmHg at 25°C
• Storage Temp.: -20°C Freezer
• Solubility: Slightly soluble in water, very slightly soluble in ethanol (96 per cen
• PKA: pKa 1.38(H2O t=20±2 N2atmosphere) (Uncertain); 7.35(H2O t=20±2 N2atmosphere) (Uncertain);10.10(H2O t=20±2 N2atmosphere) (Uncertain)
• CAS DataBase Reference: Cefadroxil(CAS DataBase Reference)
• NIST Chemistry Reference: Cefadroxil(66592-87-8)
• EPA Substance Registry System: Cefadroxil(66592-87-8)

Safety Data

• Hazard Codes: Xn,Xi
• Statements: 36/37/38-42/43
• Safety Statements: 26-36-36/37
• WGK Germany: 2
• RTECS: XI0337000
• Hazardous Substances Data: 66592-87-8(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Cefadroxil is used as an antibiotic for treating bacterial infections. It is effective against a range of bacterial pathogens, making it a valuable tool in the treatment of various infections.
Used in Veterinary Medicine:
Cefadroxil is used as a veterinary antibiotic for treating bacterial infections in animals. It is available under the brand names Cefa-Tabs and Cefa-Drops.
Used in Human Medicine:
Cefadroxil is used as an oral antibiotic for treating human bacterial infections. It is available under the brand names Duricef (Bristol-Myers Squibb) and Ultracef (Bristol Labs).

Antimicrobial activity

Resembles closely that of cefalexin

Pharmacokinetics

Oral absorption: >90% Cmax 250 mg oral: c. 9 mg/L after 1.2 h 500 mg oral: c. 18 mg/L after 1.2 h Plasma half-life: 1–1.5 h Plasma protein binding : 20% Absorption is little affected by administration with food. Distribution is similar to that of cefalexin. It is eliminated unchanged by glomerular filtration and tubular secretion; 90% of the dose appears in the urine over 24 h, most in the first 6 h, producing concentrations exceeding 500 mg/L.

Pharmacology

Cefadroxil has a broad spectrum of antimicrobial action; it is active with respect to Grampositive and Gram-negative microorganisms. Like all of the other drugs described above, it acts as a bactericide by disrupting the process of restoring the membranes of bacteria. Synonyms of this drug are bidocef, cefadril, duracef, ultracef, and others.

Clinical Use

Cefadroxil (Duricef) is an orally active semisyntheticderivative of 7-ADCA, in which the 7-acyl group is the Dhydroxylphenylglycylmoiety. This compound is absorbedwell after oral administration to give plasma levels that reach75% to 80% of those of an equal dose of its close structuralanalog cephalexin. The main advantage claimed for cefadroxilis its somewhat prolonged duration of action, whichpermits once-a-day dosing. The prolonged duration of actionof this compound is related to relatively slow urinary excretionof the drug compared with other cephalosporins, butthe basis for this remains to be explained completely. Theantibacterial spectrum of action and therapeutic indications ofcefadroxil are very similar to those of cephalexin and cephradine.The D-p-hydroxyphenylglycyl isomer is much moreactive than the L-isomer.

Clinical Use

It has been used for various community-acquired infections for which oral cephalosporins are appropriate.

Side effects

Side effects described are those common to oral cephalosporins.

Synthesis

Cefadroxil, [6R-[6α,7β(R)]]-3-methyl-8-oxo-7-[[amino(4-hydroxyphenyl) acetyl]amino]-5-thia-1-azabicyclo[4.2.0]oct-2-en-2-carboxylic acid (32.1.2.14), is an analog of cephalexin and differs only in the presence of a hydroxyl group in the fourth position of the phenyl ring of phenylglycine, and is synthesized by a scheme analogous to the scheme of cephradin synthesis.

Veterinary Drugs and Treatments

Cefadroxil is approved for oral therapy in treating susceptible infections of the skin, soft tissue, and genitourinary tract in dogs and cats. The veterinary oral tablets have been discontinued (in the USA), but human-labeled oral capsules and tablets are still available.

in vitro

the inhibitory activity of this compound was similar to that of cephalexin and cephradine when tested against 602 clinical isolates on mueller-hinton medium. in the oral treatment of experimental infections of mice, cefadroxil was more effective than cephalexin against streptococcus pyogenes, and comparably effective against streptococcus pneumoniae, staphylococcus aureus, and several gram-negative species [1].

in vivo

in mice, oral administration of cefadroxil at doses ranging from 25 to 100 mg/kg attained peak concentrations in the blood. higher peak levels were noted with cefadroxil than with cephalexin at a dose of 200 mg/kg [1].

Drug interactions

Potentially hazardous interactions with other drugs Anticoagulants: effects of coumarins may be enhanced.

Metabolism

More than 90% of a dose of cefadroxil may be excreted unchanged in the urine within 24 hours by glomerular filtration and tubular secretion.

references

[1] buck r e, price k e. cefadroxil, a new broad-spectrum cephalosporin[j]. antimicrobial agents and chemotherapy, 1977, 11(2): 324-330.[2] gerber m a, randolph m f, chanatry j, et al. once daily therapy for streptococcal pharyngitis with cefadroxil[j]. the journal of pediatrics, 1986, 109(3): 531-537.

InChI:InChI=1/C16H17N3O5S.H2O/c1-7-6-25-15-11(14(22)19(15)12(7)16(23)24)18-13(21)10(17)8-2-4-9(20)5-3-8;/h2-5,10-11,15,20H,6,17H2,1H3,(H,18,21)(H,23,24);1H2/t10?,11-,15-;/m1./s1

Relevant articles and documents

Silylation process

A process for the silylation of 6-aminopenicillanic acid or 7-amino-desacetoxy-cephalosporanic acid by silylation in certain carboxylic acid esters and its use in the production of 6-alpha-aminoacyl-penicillins and 7-alpha-aminoacyl-desacetoxy-cephalosporins.

Beta lactam production

A new process is described for the production of 6-alpha-amino-penicillins and 7-alpha-amino-desacetoxy-cephalosporins free from halogen-containing solvents by acylating 6-APA, 7-ADCA or a derivative thereof in a halogen-free solvent.

Substantially anhydrous crystalline cefadroxil and method for producing it

The invention relates to a substantially anhydrous crystalline cefadroxil having a water content between about 0.8% and 3.9%. Such cefadroxil is obtained slurrying a cefadroxil solvate of dimethylacetamide, or of N-methyl-2-pyrrolidone or of monomethylformamide, with isopropyl alcohol with up to 4% of water and preferably in the presence of methanol in an amount lower than 60%, at a temperature of about +45° C. to +55° C. and then filtering the so obtained compound.

Method for preparing crystalline cefadroxil monohydrate

The invention relates to a method for preparing crystalline cefadroxil monohydrate. According to such a method a cefadroxil solvate is slurried with isopropyl alcohol containing less 6% to 18% of water at a temperature between +45° to +55° C.: the crystalline cefadroxil monohydrate is isolated by filtration. Some of the cefadroxil solvates which can be used are novel: they are prepared by adding dimethylacetamide, N-methyl-2-pyrrolidone or monomethylformamide to an aqueous solution of cefadroxil at a pH between 5.5 and 6.

Substantially anhydrous crystalline cefadroxil and method for producing it

The invention relates to a substantially anhydrous crystalline ce-fadroxil having a water content between about 0.8% and 3.9%. Such cefadroxil is obtained slurrying a cefadroxil solvate of dimethylacetamide, or of N-methyl-2-pyrrolidone or of monomethyl-formamide, with isopropyl alcohol containing either from about 2% to 4% of water of from about 0.1% to 4% of water and from 0% to about 60% of methanol, at a temperature in the range of about +45°C to +55°C and than filtering the desired cefadroxil so obtained.

Process for preparing cephalosporanic acid compounds

A process for the preparation of [D-α-amino-p-hydroxyphenylacetamido]-penicillanic acid or cephalosporanic acid compounds comprising reacting a compound having a formula selected from the group consisting of STR1 wherein X is selected from the group consisting of hydrogen, acetoxy and five-membered heterocyclic group containing at least one hetero atom of the group consisting of oxygen, sulfur and nitrogen and optionally substituted with e.g. lower alkyl, this residue being attached to the 3-CH2 group via sulfur atom and wherein a NH radical if present has optionally been silylated with at least one mole equivalent of a silylating agent producing STR2 wherein R1, R2 and R3 are individually selected from the group consisting of lower alkyl, benzyl, cycloalkyl and phenyl in an inert anhydrous, organic solvent, preferably a water-inmiscible organic main-solvent, to form a compound having a formula selected from the group consisting of STR3 adjusting the pH to a scale value of 5.5 to 7.5 and reacting the resulting compounds in a pre-cooled solution with an at least equimolar amount of a compound of the formula wherein R4 is lower alkyl, R5 is selected from the group consisting of hydrogen and lower alkyl and R6 and R7 are lower alkoxy.

Process for the preparation of the crystalline monohydrate of 7-[D-α-aα-(p-hydroxyphenyl)acetamido]-3-methyl-3-cephem-4-carboxylic acid

A novel crystalline monohydrate of 7-[D-α-amino-α-(p-hydroxyphenyl)acetamido]-3-methyl-3-caphem-4-carboxylic acid is prepared and found to be a stable useful form of the cephalosporin antibiotic especially advantageous for pharmaceutical formulations.