Ciclacillin

Ciclacillin
Systematic (IUPAC) name
(2S,5R,6R)-6-{[(1-aminocyclohexyl)carbonyl]amino}- 3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane- 2-carboxylic acid
Clinical data
AHFS/Drugs.com International Drug Names
Routes of
administration		 Oral
Pharmacokinetic data
Bioavailability Moderate
Protein binding <25%
Identifiers
CAS Number 3485-14-1 YesY
ATC code none
PubChem CID 19003
IUPHAR/BPS 4817
DrugBank DB01000 YesY
ChemSpider 17941 YesY
UNII 72ZJ154X86 YesY
KEGG D01334 YesY
ChEBI CHEBI:31444 YesY
ChEMBL CHEMBL1200356 N
Chemical data
Formula C15H23N3O4S
Molar mass 341.425 g/mol
 NYesY (what is this?)  (verify)

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Ciclacillin has been superseded by newer antibiotics and is no longer in clinical use, at least in the United States.[5]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).

Interestingly, this artifice seems to have worked, since cyclacillin is more active in vivo than its in vitro spectrum suggests would be likely.

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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