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  Y
PubChem CID	19003
IUPHAR/BPS	4817
DrugBank	DB01000  Y
ChemSpider	17941  Y
UNII	72ZJ154X86
KEGG	D01334  Y
ChEBI	CHEBI:31444  Y
ChEMBL	ChEMBL1200356  N
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 Y Key:HGBLNBBNRORJKI-WCABBAIRSA-N Y
NY  (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Ciclacillin has been superseded by newer antibiotics and is no longer in clinical use, at least in the United States.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:

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

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

• Scheld WM, Sydnor A, Farr B, Gratz JC, Gwaltney JM (September 1986). "Comparison of cyclacillin and amoxicillin for therapy for acute maxillary sinusitis". Antimicrobial Agents and Chemotherapy. 30 (3): 350–353. doi:10.1128/aac.30.3.350. PMC   180557 . PMID   3535660.