Azlocillin

Originator

Securopen,Bayer,W. Germany,1977

Uses

Antibacterial.

Uses

Azlocillin is an antibiotic.

Definition

ChEBI: A semisynthetic penicillin antibiotic used in treating infections caused by Pseudomonas aeruginosa, Escherichia coli, and Haemophilus influenzae.

Indications

Azlocillin is active with respect to Gram-positive and Gram-negative aerobic and anaerobic microorganisms. It is highly effective with respect to bacillus pyocyaneus, including strains that are resistant to carbenicillin and aminoglycosides. It is destroyed by betalactamases. It is used for bacterial infections such as pyelonephritis, uretritis, cystitis, endometritis, cholecystitis, sepsis, peritonitis, endocarditis, meningitis, pneumonia, infections of the skin and soft tissues, infected burns, and so on. Synonyms of this drug are securopen and azlin.

Manufacturing Process

3.8 parts by weight of D-(-)-α-[(imidazolidin-2-on-1-yl)carbonylamino]phenylacetic acid were dissolved in 65 parts by volume of dichloromethane. 2.7 parts by weight of 1-methyl-2-chloro-δ1-pyrrolinium chloride were added, and after cooling to -10°C 2.0 parts by volume of triethylamine were added gradually. This reaction mixture was then stirred for one hour at -5°C (mixture A). 4.0 parts by weight of 6-aminopenicillanic acid in 80 parts by volume of dichloromethane were treated with 4.4 parts by volume of triethylamine and 4.0 parts by weight of anhydrous sodium sulfate and then stirred for two hours at room temperature. After filtration, the solution was cooled to -20°C and combined with the mixture A. The reaction mixture was left to reach 0°C of its own accord, and was then stirred for a further hour at 0°C. The solvent was removed in a rotary evaporator, the residue was dissolved in water, and the solution was covered with a layer of ethyl acetate and acidified with dilute hydrochloric acid at 0° to 5°C, while stirring, until pH 1.5 was reached. The organic phase was then separated off, washed with water, dried over magnesium sulfate while cooling, and filtered, and after dilution with an equal amount of ether the sodium salt of the penicillin was precipitated from the filtrate by adding a solution of sodium 2-ethylcaproate dissolved in ether containing methanol. Yield: 1.3 parts by weight.

brand name

Azlin (Bayer).

Therapeutic Function

Antibacterial

Antimicrobial activity

A semisynthetic acylureidopenicillin supplied as the sodium salt for parenteral administration. It is active against a wide range of other Gram-negative bacteria, but is distinguished mainly by its activity against Ps. aeruginosa. B. fragilis and other anaerobes are moderately susceptible. Like other ureidopenicillins, azlocillin is active against Grampositive cocci, H. influenzae and N. gonorrhoeae. Because it can be hydrolyzed by most β-lactamases, β-lactamase-producing isolates are resistant.
It attains peak concentrations of 250 mg/L after a 3 g intravenous infusion, with a plasma half-life of approximately 1 h. Protein binding is 20–30%. It distributes into multiple tissues and human body fluids at therapeutically useful concentrations. Up to 60% of the dose is recoverable from the urine, mostly unchanged, although some hydrolysis of the β-lactam ring takes place in the body.
Toxicity and side effects are similar to those associated with carboxypenicillins. Its clinical use is for serious infections with susceptible organisms, including lower respiratory tract, intra-abdominal, urinary tract and gynecological infections. Commercial availability is quite limited.

Synthesis

Azlocillin, (2S,5R,6R)-3,3-dimethyl-7-oxo-6-[(R)-2-(2-oxoimidazolidin-1-carboxamido)-2-phenylacetamido]-4-thia-1-azabicyclo[3.2.0]-heptan-2-carboxylic acid (32.1.1.24), is synthesized by the following scheme. 2-Imidazolidinone is acylated with phosgene, forming 1-chlorocarbonyl-2-imidazolidinone (32.1.1.22). The resulting 1-chlorocarbonyl-2-imidazolidinone (32.1.1.22) is reacted with D()-|á-phenylglycine, forming N-(2-oxoimidazolidin- 1-carboxamido)-phenylglycine (32.1.1.23). Reacting this with 6-APA in the presence of triethylamine gives the desired azlocillin (32.1.1.24).

References

[1] Patent: CN105753886, 2016, A. Location in patent: Paragraph 0032; 0033; 0034; 0035; 0036; 0037
[2] European Journal of Medicinal Chemistry, 1982, vol. 17, # 1, p. 59 - 63
[3] Patent: CN105777778, 2016, A. Location in patent: Paragraph 0031; 0032; 0033; 0034; 0035; 0036; 0037