Ciclacillin was synthesized by Wyeth Laboratories in 1967 in the course of studies on the improvement of oral absorption of ampicillin. Although its antibacterial activity is one-sixteenth to one-half that of ampicillin, it shows a four to tenfold higher oral absorption and higher urinary excretion. Ciclacillin shows less tendency than ampicillin to cause diarrhea and is used for therapy of pyoderma, wound infection, respiratory and urinary tract infections, as well as ear and nose, and other infections caused by Staphylococcus, Streptococcus, Escherichia coli, Citrobacter, Klebsiella, Proteus, and Haemophilus influenzae.
UItracillin,Gruenenthal,W. Germany,1972
Cyclacillin is an aminosalicylic semisynthetic penicillin; Antibiotic.
ChEBI: Cyclacillin is a penicillin. It has a role as an antibacterial drug.
To 21.6 g (0.10 mol) of 6-aminopenicillanic acid (6-APA) and 213 ml of
methylene chloride in a dry 500 ml 3-neck flask fitted with stirrer,
thermometer, nitrogen inlet and reflux condenser with drying tube, 25.3 g
(0.25 mol) of triethylamine and 13.4 g (0.11 mol) of N,N-dimethylaniline were
added. After stirring at reflux for one hour, the mixture was cooled and 21.7 g
(0.20 mol) of trimethylchlorosilane was added dropwise at 12° to 15°C
The mixture was refluxed for 45 minutes, cooled under nitrogen, and 19.8 g
(0.10 mol) of 1-amino-1-cyclohexane-carboxylic acid chloride HCl was added
portionwise at -10°C over 20 minutes. The mixture was stirred for an
additional hour while the temperature rose to 20°C. The reaction mixture was
poured into 200 ml of cold water with stirring and the two-phase mixture
clarified by filtration. Dilute sodium hydroxide solution was added to the
filtrate at 5° to 10°C to pH 5.4.
After stirring overnight at room temperature, the crystalline product was
collected by filtration, washed with water and finally with acetone, and then
dried at 45°C; yield of dihydrate, 29.9 g or 79% of theory based on 6-APA;
iodometric assay, 922 mcg per mg; bioassay, 921 mcg per mg, as described
in US Patent 3,478,018.
The structure differs from other aminopenicillins in that the
benzene ring is completely saturated and the amino substituent
is attached directly to it instead of being linked to an
adjacent carbon atom. It is less active than ampicillin against
staphylococci, streptococci and H. influenzae, but is better
absorbed by mouth, peak plasma levels of 10–18 mg/L being
reached after a 500 mg oral dose. Its pharmacokinetic properties,
side effects and use resemble those of ampicillin. It has
limited availability.
