Ciclacillin

Ciclacillin
Clinical data
AHFS/Drugs.com	International Drug Names
Routes of; administration	Oral
ATC code	none;
Pharmacokinetic data
Bioavailability	Moderate
Protein binding	<25%
Identifiers
	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;
CAS Number	3485-14-1 ;
PubChem CID	19003;
IUPHAR/BPS	4817;
DrugBank	DB01000 ;
ChemSpider	17941 ;
UNII	72ZJ154X86;
KEGG	D01334 ;
ChEBI	CHEBI:31444 ;
ChEMBL	ChEMBL1200356 ;
CompTox Dashboard (EPA)	DTXSID9022861 ;
ECHA InfoCard	100.020.429
Chemical and physical data
Formula	C15H23N3O4S
Molar mass	341.43 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES O=C(O)[C@@H]2N3C(=O)[C@@H](NC(=O)C1(N)CCCCC1)[C@H]3SC2(C)C;
	InChI 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 ; Key:HGBLNBBNRORJKI-WCABBAIRSA-N ;
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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Ciclacillin has been superseded by newer antibiotics and is no longer in clinical use, at least in the United States.^[5]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.

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]}

References

^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.

Synthesis

References

Further reading