Ciclacillin

Ciclacillin (INN) or cyclacillin (USAN), trade names Cyclapen, Cyclapen-W, Vastcillin, and others, is an aminopenicillin antibiotic. Its spectrum of activity is similar to that of ampicillin, although it is less susceptible to beta-lactamases than ampicillin and has much higher bioavailability.[1] A large randomized, double-blind clinical trial published in 1978 also showed that ciclacillin is associated with significantly fewer and milder adverse effects than ampicillin;[2] later studies seemed to confirm this improved tolerability, at least in children.[3][4]

Ciclacillin
Clinical data
AHFS/Drugs.comInternational Drug Names
Routes of
administration		Oral
ATC code
  • none
Pharmacokinetic data
BioavailabilityModerate
Protein binding<25%
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.020.429
Chemical and physical data
FormulaC15H23N3O4S
Molar mass341.43 g·mol−1
3D model (JSmol)
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Ciclacillin has been superseded by newer antibiotics and is no longer in clinical use, at least in the United States.[5]

Synthesis

In an attempt to form orally active penicillins unrelated to ampicillin, use was made of the fact that certain spiro α-amino acids, such as Cycloleucine, are well absorbed orally and transported like normal amino acids.

Cyclacillin synthesis:[6]

Reaction of cyclohexanone with ammonium carbonate and KCN under the conditions of the Bucherer-Bergs reaction led to hydantoin 1. On acid hydrolysis, α-amino acid 2 resulted. Treatment with phosgene both protected the amino group and activated the carboxyl group toward amide formation (as 3) and reaction with 6-aminopenicillanic acid (6-APA) gave cyclacillin (4).

This artifice seems to have worked, since cyclacillin is more active in vivo than its in vitro spectrum suggests.

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References
  1. Warren GH (1976). "Cyclacillin: microbiological and pharmacological properties and use in chemotherapy of infection - a critical appraisal". Chemotherapy. 22 (3–4): 154–82. doi:10.1159/000221924. PMID 773605.
  2. Gold JA, Hegarty CP, Deitch MW, Walker BR (January 1979). "Double-blind clinical trials of oral cyclacillin and ampicillin". Antimicrob Agents Chemother. 15 (1): 55–8. doi:10.1128/aac.15.1.55. PMC 352600. PMID 371540.
  3. McLinn SE, Goldberg F, Kramer R, Saltstein E, Bomze JP, Deitch MW (October 1982). "Double-blind multicenter comparison of cyclacillin and amoxicillin for the treatment of acute otitis media". J Pediatr. 101 (4): 617–21. doi:10.1016/S0022-3476(82)80724-5. PMID 6750067.
  4. McLinn SE, Kaplan J, West N (1983). "Multicenter comparison of cyclacillin and amoxicillin in the treatment of acute streptococcal pharyngitis". Clin Ther. 5 (3): 299–304. PMID 6342785.
  5. Gorbach SL, Bartlett JG, Blacklow NR (2004). Infectious diseases (3rd ed.). Hagerstown, MD: Lippincott Williams & Wilkins. p. 186. ISBN 0-7817-3371-5. Retrieved on September 7, 2008 through Google Book Search.
  6. Alburn, H. E.; Clark, R. E.; Fletcher h, 3rd; Grant, N. H. (1967). "Synthesis of new broad-spectrum aminoalicyclic penicillins". Antimicrobial Agents and Chemotherapy. 7: 586–9. PMID 5596194.

Further reading


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