Cefadroxil

Structural formula
General
Non-proprietary name	Cefadroxil
other names	(6 R , 7 R ) -7 - [( R ) -2-Amino-2- (4-hydroxyphenyl) acetamino] -3-methyl-8-oxo-5-thia-1-azabicyclo [4.2.0] oct -2-en-2-carboxylic acid ( IUPAC ); Cefadroxilum ( Latin );
Molecular formula	C 16 H 17 N 3 O 5 S; C 16 H 17 N 3 O 5 S · H 2 O (monohydrate) ;
External identifiers / databases
EC number	256-555-6
ECHA InfoCard	100.051.397
PubChem	47965
ChemSpider	43630
DrugBank	DB01140
Wikidata	Q2319020
Drug information
ATC code	J01 DB05
Drug class	β-lactam antibiotic; 1st generation cephalosporins;
Mechanism of action	Disturbance of the cell wall synthesis of the bacteria
properties
Molar mass	363.39 g · mol -1
Physical state	firmly
Melting point	197 ° C
solubility	1110 mg l −1
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
H and P phrases	H: 315-317-319-334-317-335
	P: 261-264-280-304 + 340 + 312-342 + 311
Toxicological data	10 g kg −1 ( LD 50 , rat , oral )
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Cefadroxil is an antibiotic used to treat infections of the urinary tract, skin, and skin structure. The drug is produced semisynthetically and belongs to the class of cephalosporins of the 1st generation.

Cefadroxil was patented by Bristol-Myers Squibb in 1969 and 1970 . As a finished product, it was in Germany in 1979 under the trade name Grüncef for marketing approved .

properties

Cefadroxil is a yellowish white, finely crystalline powder. Cefadroxil has a broad spectrum of activity, which includes streptococci and staphylococci , for example . Cefadroxil can also be helpful in the following infections: Staphylococcus epidermidis , Escherichia coli , various types of Klebsiella , Haemophilus influenzae , Proteus mirabilis , Salmonella , Shigella , Neisseria gonorrhoeae and Neisseria meningitidis .

Indications

Cefadroxil is indicated for the treatment of infections caused by germs sensitive to cefadroxil, for example of the respiratory tract, the ear, nose and throat area, the urinary and genital organs, the skin and soft tissue, the bones and joints as well as in the field of gynecology and obstetrics.

Working principle

The cefadroxil molecules bind to specific penicillin- binding proteins , which are located in the bacterial cell wall. This prevents further synthesis of the bacterial cell wall. Cefadroxil acts on sensitive growing germs even in low concentrations. More than 90% of the antibiotic is excreted in the urine within 24 hours.

Application

Cefadroxil is given orally and is quickly absorbed into the bloodstream . The absorption is not reduced by food intake.

Side effects

In addition to the desired effects, Cefadroxil can also cause some side effects. This includes, for example, nausea, vomiting, diarrhea, allergic rashes as well as chills, fever and headaches, sore throats or abdominal pain.

synthesis

The synthesis of cefadroxil takes place via a semisynthesis , which in this case means the acylation of an amino group . The 7-aminodesacetoxycephalosporanic acid (7-ADCA for short) to be acylated is converted from penicillin G with the help of N , N ′ -bis (trimethylsilyl) urea through a chemical reaction .

Two synthetic routes are known for the synthesis of cefadroxil:

In the first way, 7-ADCA ( 2 ) reacts under basic conditions with ( R ) -hydroxyphenylglycine ester ( 1 ), the amino group of which is protected by a tert- butyloxycarbonyl group. At the end of the reaction, the protective group is removed by formic acid and the cefadroxil molecule is formed.

Reaction of 7-ADCA and hydroxyphenylglycine ester to form cefadroxil

In the second synthetic route, the 7-ADCA ( 2 ) reacts with ( R ) -4-hydroxyphenylglycine ( 3 ). With the addition of ethyl chloroformate and triethylamine and with elimination of the acetoacetic ester protective group, the desired cefadroxil ( 4 ) is formed.

Reaction of 7-ADCA and ( R ) -4-hydroxyphenylglycine to form cefadroxil

Individual evidence

↑ ^a ^b ^c ^d ^e ^f Entry on Cefadroxil. In: Römpp Online . Georg Thieme Verlag, accessed on March 13, 2019.
↑ ^a ^b Data sheet Cefadroxil C7020 from Sigma-Aldrich , accessed on March 13, 2019 ( PDF ).
^ Axel Kleemann , Jürgen Engel, Bernd Kutscher and Dieter Reichert: Pharmaceutical Substances , Thieme-Verlag Stuttgart, 5th edition (2009), pp. 232-233, ISBN 978-3-13-558405-8 ; also online with biannual additions and updates.
↑ ^a ^b ^c Entry on cefadroxil in the DrugBank of the University of Alberta , accessed March 13, 2019.
↑ ^a ^b Grüncef 1 g tablets . Technical information, as of November 2018. Infectopharm Arzneimittel and Concilium GmbH.
↑ Cefadroxil Side Effects in detail. Retrieved March 13, 2019 .
↑ Alle Bruggink (Ed.): Synthesis of β-Lactam Antibiotics: Chemistry, Biocatalysis & Process Integration. Springer Science + Business Media, ISBN 978-0-7923-7060-4 , p. 15 .

[Römpp-1] ↑ ^a ^b ^c ^d ^e ^f Entry on Cefadroxil. In: Römpp Online . Georg Thieme Verlag, accessed on March 13, 2019.

[Sigma-2] Data sheet Cefadroxil C7020 from Sigma-Aldrich , accessed on March 13, 2019 ( PDF ).

[Kleemann-3] Axel Kleemann , Jürgen Engel, Bernd Kutscher and Dieter Reichert: Pharmaceutical Substances , Thieme-Verlag Stuttgart, 5th edition (2009), pp. 232-233, ISBN 978-3-13-558405-8 ; also online with biannual additions and updates.

[:1-4] Entry on cefadroxil in the DrugBank of the University of Alberta , accessed March 13, 2019.

[grüncef-5] Grüncef 1 g tablets . Technical information, as of November 2018. Infectopharm Arzneimittel and Concilium GmbH.

[6] Cefadroxil Side Effects in detail. Retrieved March 13, 2019 .

[7] Alle Bruggink (Ed.): Synthesis of β-Lactam Antibiotics: Chemistry, Biocatalysis & Process Integration. Springer Science + Business Media, ISBN 978-0-7923-7060-4 , p. 15 .