Ciclacillin

Last updated
Ciclacillin
Ciclacillin.svg
Clinical data
AHFS/Drugs.com International Drug Names
Routes of
administration
Oral
ATC code
  • none
Pharmacokinetic data
Bioavailability Moderate
Protein binding <25%
Identifiers
  • (2S,5R,6R)-6-{[(1-aminocyclohexyl)carbonyl]amino}- 3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane- 2-carboxylic acid
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.020.429 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C15H23N3O4S
Molar mass 341.43 g·mol−1
3D model (JSmol)
  • O=C(O)[C@@H]2N3C(=O)[C@@H](NC(=O)C1(N)CCCCC1)[C@H]3SC2(C)C
  • InChI=1S/C15H23N3O4S/c1-14(2)9(12(20)21)18-10(19)8(11(18)23-14)17-13(22)15(16)6-4-3-5-7-15/h8-9,11H,3-7,16H2,1-2H3,(H,17,22)(H,20,21)/t8-,9+,11-/m1/s1 Yes check.svgY
  • Key:HGBLNBBNRORJKI-WCABBAIRSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (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]

Contents

Ciclacillin has been superseded by newer antibiotics and is no longer in clinical use, at least in the United States.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: Cyclacillin synthesis.svg
Cyclacillin synthesis:

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.[ citation needed ]

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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): 154–182. 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". Antimicrobial Agents and Chemotherapy. 15 (1): 55–58. 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". The Journal of Pediatrics. 101 (4): 617–621. 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". Clinical Therapeutics. 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 HE, Clark RE, Fletcher H, Grant NH (1967). "Synthesis of new broad-spectrum aminoalicyclic penicillins". Antimicrobial Agents and Chemotherapy. 7: 586–589. PMID   5596194.

Further reading