Identification

Name
Cyclacillin
Accession Number
DB01000  (APRD00892)
Type
Small Molecule
Groups
Approved
Description

A cyclohexylamido analog of penicillanic acid. [PubChem]

Structure
Thumb
Synonyms
  • (1-Aminocyclohexyl)penicillin
  • (2S,5R,6R)-6-{[(1-aminocyclohexyl)carbonyl]amino}-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid
  • 6-(1-Aminocyclohexanecarboxamido)penicillanic acid
  • 6-(1-Aminocyclohexylcarboxamido)penicillanic acid
  • Aminocyclohexylpenicillin
  • Bastcillin
  • Calthor
  • Ciclacilina
  • Ciclacillin
  • Ciclacilline
  • Ciclacillinum
  • Ciclacillum
  • Citosarin
  • Cyclacillin
  • Cyclapen
  • Cyclapen-W
  • Syngacillin
  • Ultracillin
  • Vastcillin
  • Vipicil
  • Wyvital
International/Other Brands
Bastcillin / Calthor / Citosarin / Cyclapen (Wyeth) / Cyclapen-W (Wyeth) / Orfilina / Syngacillin / Ultracillin / Vastcillin (Takeda) / Vipicil (Wyeth) / Wybital (Wyeth) / Wyvital
Categories
UNII
72ZJ154X86
CAS number
3485-14-1
Weight
Average: 341.426
Monoisotopic: 341.140926929
Chemical Formula
C15H23N3O4S
InChI Key
HGBLNBBNRORJKI-WCABBAIRSA-N
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
IUPAC Name
(2S,5R,6R)-6-(1-aminocyclohexaneamido)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid
SMILES
[H][C@]12SC(C)(C)[C@@H](N1C(=O)[C@H]2NC(=O)C1(N)CCCCC1)C(O)=O

Pharmacology

Indication

For the treatment of bacterial infections caused by susceptible organisms.

Pharmacodynamics

Cyclacillin, a penicillin, is a cyclohexylamido analog of penicillanic acid. Cyclacillin is more resistant to beta-lactamase hydrolysis than ampicillin, is much better absorbed when given by mouth and, as a result, the levels reached in the blood and in the urine are considerably higher than those obtained with the same dose of ampicillin. Cyclacillin has been replaced by newer penicillin treatments.

Mechanism of action

The bactericidal activity of cyclacillin results from the inhibition of cell wall synthesis via affinity for penicillin-binding proteins (PBPs). Cyclacillin is stable in the presence of a variety of b-lactamases, including penicillinases and some cephalosporinases.

TargetActionsOrganism
APenicillin-binding protein 1A
inhibitor
Clostridium perfringens (strain 13 / Type A)
APenicillin-binding protein 1A
inhibitor
Streptococcus pneumoniae (strain ATCC BAA-255 / R6)
APenicillin-binding protein 3
inhibitor
Streptococcus pneumoniae
APenicillin binding protein 2a
inhibitor
Staphylococcus aureus
Absorption

Moderately absorbed.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

Symptoms of overdose include severe diarrhea, nausea and vomiting.

Affected organisms
  • Enteric bacteria and other eubacteria
  • Streptococcus pneumoniae
  • Haemophilus influenzae
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AcenocoumarolCyclacillin may increase the anticoagulant activities of Acenocoumarol.
AmikacinThe serum concentration of Amikacin can be decreased when it is combined with Cyclacillin.
ApramycinThe serum concentration of Apramycin can be decreased when it is combined with Cyclacillin.
ArbekacinThe serum concentration of Arbekacin can be decreased when it is combined with Cyclacillin.
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Cyclacillin.
BekanamycinThe serum concentration of Bekanamycin can be decreased when it is combined with Cyclacillin.
ChlortetracyclineThe therapeutic efficacy of Cyclacillin can be decreased when used in combination with Chlortetracycline.
ClorindioneCyclacillin may increase the anticoagulant activities of Clorindione.
DemeclocyclineThe therapeutic efficacy of Cyclacillin can be decreased when used in combination with Demeclocycline.
DesogestrelThe metabolism of Desogestrel can be increased when combined with Cyclacillin.
Food Interactions
Not Available

References

Synthesis Reference

Alburn, H.E., Grant, N.H. and Fletcher, H. Ill; US.Patent 3,194,802; assigned to American Home Products Corporation. Robinson, C.A. and Nescio, J.J.; US.Patent 3,478,018; November 11,1969; assigned to American Home Products Corporation.

General References
Not Available
External Links
Human Metabolome Database
HMDB0015135
KEGG Drug
D01334
KEGG Compound
C12766
PubChem Compound
19003
PubChem Substance
46508073
ChemSpider
17941
BindingDB
50350474
ChEBI
31444
ChEMBL
CHEMBL1200356
Therapeutic Targets Database
DAP001159
PharmGKB
PA164743456
Wikipedia
Cyclacillin
ATC Codes
J01CR50 — Combinations of penicillins

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
  • Wyeth ayerst laboratories
  • Teva pharmaceuticals usa inc
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)182-183 °CPhysProp
logP1.31SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility1.9 mg/mLALOGPS
logP0.56ALOGPS
logP-1.9ChemAxon
logS-2.3ALOGPS
pKa (Strongest Acidic)3.3ChemAxon
pKa (Strongest Basic)8.45ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area112.73 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity84.22 m3·mol-1ChemAxon
Polarizability34.81 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.947
Blood Brain Barrier-0.9961
Caco-2 permeable-0.8171
P-glycoprotein substrateSubstrate0.7143
P-glycoprotein inhibitor INon-inhibitor0.9153
P-glycoprotein inhibitor IINon-inhibitor0.997
Renal organic cation transporterNon-inhibitor0.9488
CYP450 2C9 substrateNon-substrate0.8429
CYP450 2D6 substrateNon-substrate0.825
CYP450 3A4 substrateNon-substrate0.5
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.8594
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9839
Ames testNon AMES toxic0.8339
CarcinogenicityNon-carcinogens0.8335
BiodegradationNot ready biodegradable0.9667
Rat acute toxicity1.8643 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9994
hERG inhibition (predictor II)Non-inhibitor0.8895
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as penicillins. These are organic compounds containing the penicillin core structure, which is structurally characterized by a penam ring bearing two methyl groups at position 2, and an amide group at position 6 [starting from the sulfur atom at position 1].
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Lactams
Sub Class
Beta lactams
Direct Parent
Penicillins
Alternative Parents
N-acyl-alpha amino acids and derivatives / Alpha amino acid amides / Cyclohexylamines / Thiazolidines / Tertiary carboxylic acid amides / Secondary carboxylic acid amides / Amino acids / Azetidines / Thiohemiaminal derivatives / Monocarboxylic acids and derivatives
show 8 more
Substituents
Penicillin / N-acyl-alpha amino acid or derivatives / Alpha-amino acid amide / Alpha-amino acid or derivatives / Cyclohexylamine / Thiazolidine / Tertiary carboxylic acid amide / Amino acid or derivatives / Azetidine / Amino acid
show 21 more
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
penicillin (CHEBI:31444)

Targets

Kind
Protein
Organism
Clostridium perfringens (strain 13 / Type A)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Transferase activity, transferring glycosyl groups
Specific Function
Cell wall formation. Synthesis of cross-linked peptidoglycan from the lipid intermediates. The enzyme has a penicillin-insensitive transglycosylase N-terminal domain (formation of linear glycan str...
Gene Name
pbpA
Uniprot ID
Q8XJ01
Uniprot Name
Penicillin-binding protein 1A
Molecular Weight
75176.35 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
Kind
Protein
Organism
Streptococcus pneumoniae (strain ATCC BAA-255 / R6)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Penicillin binding
Specific Function
Cell wall formation.
Gene Name
pbpA
Uniprot ID
Q8DR59
Uniprot Name
Penicillin-binding protein 1A
Molecular Weight
79700.9 Da
References
  1. Williamson R, Hakenbeck R, Tomasz A: In vivo interaction of beta-lactam antibiotics with the penicillin-binding proteins of Streptococcus pneumoniae. Antimicrob Agents Chemother. 1980 Oct;18(4):629-37. [PubMed:7447421]
Kind
Protein
Organism
Streptococcus pneumoniae
Pharmacological action
Yes
Actions
Inhibitor
General Function
Serine-type d-ala-d-ala carboxypeptidase activity
Specific Function
Not Available
Gene Name
pbp3
Uniprot ID
Q75Y35
Uniprot Name
Penicillin-binding protein 3
Molecular Weight
45209.84 Da
References
  1. Williamson R, Hakenbeck R, Tomasz A: In vivo interaction of beta-lactam antibiotics with the penicillin-binding proteins of Streptococcus pneumoniae. Antimicrob Agents Chemother. 1980 Oct;18(4):629-37. [PubMed:7447421]
Kind
Protein
Organism
Staphylococcus aureus
Pharmacological action
Yes
Actions
Inhibitor
General Function
Penicillin binding
Specific Function
Not Available
Gene Name
mecA
Uniprot ID
C1KC03
Uniprot Name
Penicillin binding protein 2a
Molecular Weight
54918.915 Da
References
  1. Williamson R, Hakenbeck R, Tomasz A: In vivo interaction of beta-lactam antibiotics with the penicillin-binding proteins of Streptococcus pneumoniae. Antimicrob Agents Chemother. 1980 Oct;18(4):629-37. [PubMed:7447421]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Symporter activity
Specific Function
Sodium-ion dependent, high affinity carnitine transporter. Involved in the active cellular uptake of carnitine. Transports one sodium ion with one molecule of carnitine. Also transports organic cat...
Gene Name
SLC22A5
Uniprot ID
O76082
Uniprot Name
Solute carrier family 22 member 5
Molecular Weight
62751.08 Da
References
  1. Ganapathy ME, Huang W, Rajan DP, Carter AL, Sugawara M, Iseki K, Leibach FH, Ganapathy V: beta-lactam antibiotics as substrates for OCTN2, an organic cation/carnitine transporter. J Biol Chem. 2000 Jan 21;275(3):1699-707. [PubMed:10636865]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Proton-dependent oligopeptide secondary active transmembrane transporter activity
Specific Function
Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides. May constitute a major route for the absorption of protein digestion end-products.
Gene Name
SLC15A1
Uniprot ID
P46059
Uniprot Name
Solute carrier family 15 member 1
Molecular Weight
78805.265 Da
References
  1. Ganapathy ME, Brandsch M, Prasad PD, Ganapathy V, Leibach FH: Differential recognition of beta -lactam antibiotics by intestinal and renal peptide transporters, PEPT 1 and PEPT 2. J Biol Chem. 1995 Oct 27;270(43):25672-7. [PubMed:7592745]
  2. Luckner P, Brandsch M: Interaction of 31 beta-lactam antibiotics with the H+/peptide symporter PEPT2: analysis of affinity constants and comparison with PEPT1. Eur J Pharm Biopharm. 2005 Jan;59(1):17-24. [PubMed:15567297]
  3. Terada T, Saito H, Mukai M, Inui K: Recognition of beta-lactam antibiotics by rat peptide transporters, PEPT1 and PEPT2, in LLC-PK1 cells. Am J Physiol. 1997 Nov;273(5 Pt 2):F706-11. [PubMed:9374833]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Peptide:proton symporter activity
Specific Function
Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides.
Gene Name
SLC15A2
Uniprot ID
Q16348
Uniprot Name
Solute carrier family 15 member 2
Molecular Weight
81782.77 Da
References
  1. Ganapathy ME, Brandsch M, Prasad PD, Ganapathy V, Leibach FH: Differential recognition of beta -lactam antibiotics by intestinal and renal peptide transporters, PEPT 1 and PEPT 2. J Biol Chem. 1995 Oct 27;270(43):25672-7. [PubMed:7592745]
  2. Terada T, Saito H, Mukai M, Inui K: Recognition of beta-lactam antibiotics by rat peptide transporters, PEPT1 and PEPT2, in LLC-PK1 cells. Am J Physiol. 1997 Nov;273(5 Pt 2):F706-11. [PubMed:9374833]
  3. Luckner P, Brandsch M: Interaction of 31 beta-lactam antibiotics with the H+/peptide symporter PEPT2: analysis of affinity constants and comparison with PEPT1. Eur J Pharm Biopharm. 2005 Jan;59(1):17-24. [PubMed:15567297]

Drug created on June 13, 2005 07:24 / Updated on August 02, 2018 04:30