Ciclacillin

Ciclacillin

File: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
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 checkY
PubChem CID	19003
IUPHAR/BPS	4817
DrugBank	DB01000 checkY
ChemSpider	17941 checkY
UNII	72ZJ154X86
KEGG	D01334 checkY
ChEBI	CHEBI:31444 checkY
ChEMBL	ChEMBL1200356 ☒N
E number	{{#property:P628}}
CompTox Dashboard (EPA)	{{#property:P3117}}
ECHA InfoCard	{{#property:P2566}}
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 checkY Key:HGBLNBBNRORJKI-WCABBAIRSA-N checkY
☒NcheckY (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. 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; later studies seemed to confirm this improved tolerability, at least in children.

Ciclacillin has been superseded by newer antibiotics and is no longer in clinical use, at least in the United States.

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.

File: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.