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Ciclacillin has been superseded by newer antibiotics and is no longer in clinical use, at least in the United States.^[5]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