You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NameHetacillin
Accession NumberDB00739  (APRD01012)
TypeSmall Molecule
GroupsApproved, Vet Approved, Withdrawn
DescriptionHetacillin is a penicillin beta-lactam antibiotic used in the treatment of bacterial infections caused by susceptible, usually gram-positive, organisms. The name "penicillin" can either refer to several variants of penicillin available, or to the group of antibiotics derived from the penicillins. Hetacillin has in vitro activity against gram-positive and gram-negative aerobic and anaerobic bacteria. The bactericidal activity of Hetacillin results from the inhibition of cell wall synthesis and is mediated through Hetacillin binding to penicillin binding proteins (PBPs). Hetacillin has been withdrawn from the market since it has been discovered that it has no therapeutic advantage compared to non-ester derivatives like ampicillin.
Structure
Thumb
Synonyms
(2S,5R,6R)-6-[(4R)-2,2-Dimethyl-5-oxo-4-phenylimidazolidin-1-yl]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid
6beta-[(4R)-2,2-Dimethyl-5-oxo-4-phenylimidazolidin-1-yl]penicillanic acid
Hetacilina
Hetacillin
Hétacilline
Hetacillinum
Phenazacillin
External Identifiers
  • BL-P 804
  • BRL 804
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
NatacillinBristol-Myers Squibb
VersapenBristol-Myers Squibb
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Hetacillin Potassium
ThumbNot applicableDBSALT000966
Categories
UNIITN4JSC48CV
CAS number3511-16-8
WeightAverage: 389.469
Monoisotopic: 389.140926929
Chemical FormulaC19H23N3O4S
InChI KeyDXVUYOAEDJXBPY-NFFDBFGFSA-N
InChI
InChI=1S/C19H23N3O4S/c1-18(2)13(17(25)26)21-15(24)12(16(21)27-18)22-14(23)11(20-19(22,3)4)10-8-6-5-7-9-10/h5-9,11-13,16,20H,1-4H3,(H,25,26)/t11-,12-,13+,16-/m1/s1
IUPAC Name
(2S,5R,6R)-6-[(4R)-2,2-dimethyl-5-oxo-4-phenylimidazolidin-1-yl]-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)[[email protected]]2N1C(=O)[[email protected]](NC1(C)C)C1=CC=CC=C1)C(O)=O
Pharmacology
IndicationHetacillin is a beta-lactam antibiotic prodrug used to treat bacterial infections. In the body it gets converted to ampicillin.
Structured Indications Not Available
PharmacodynamicsHetacillin is a penicillin beta-lactam antibiotic used in the treatment of bacterial infections caused by susceptible, usually gram-positive, organisms. The name "penicillin" can either refer to several variants of penicillin available, or to the group of antibiotics derived from the penicillins. Hetacillin has in vitro activity against gram-positive and gram-negative aerobic and anaerobic bacteria. The bactericidal activity of Hetacillin results from the inhibition of cell wall synthesis and is mediated through Hetacillin binding to penicillin binding proteins (PBPs).
Mechanism of actionHetacillin is a semisynthetic penicillin prodrug which itself has no antibacterial activity, but is converted in the body to ampicillin and has actions and uses similar to those of ampicillin. Hetacillin is prepared by reacting ampicillin with acetone. Ampicillin rapidly decomposes because of the intramolecular attack of the side chain amino group on the lactam ring. Hetacillin locks up the offending amino group and prevents the decompolsition Hetacillin, once hydrolyzed to ampicillin (and acetone) binds to the penicillin binding proteins found in susceptible bacteria. This inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins. Targets below reflect ampicillin targets.
TargetKindPharmacological actionActionsOrganismUniProt ID
Penicillin-binding protein 2aProteinyes
inhibitor
Streptococcus pneumoniae (strain ATCC BAA-255 / R6)Q8DNB6 details
Penicillin-binding protein 1bProteinyes
inhibitor
Streptococcus pneumoniae (strain ATCC BAA-255 / R6)Q7CRA4 details
Penicillin-binding protein 3Proteinyes
inhibitor
Streptococcus pneumoniaeQ75Y35 details
Penicillin-binding protein 1AProteinyes
inhibitor
Streptococcus pneumoniae (strain ATCC BAA-255 / R6)Q8DR59 details
Penicillin-binding protein 2BProteinyes
inhibitor
Streptococcus pneumoniae (strain ATCC BAA-255 / R6)P0A3M6 details
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Hydrolyzed to active ampicillin via esterases

Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Enteric bacteria and other eubacteria
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available
References
Synthesis Reference

U.S. Patent 3,198,804.

General ReferencesNot Available
External Links
ATC CodesJ01CA18
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.5
Blood Brain Barrier-0.991
Caco-2 permeable-0.7602
P-glycoprotein substrateSubstrate0.5297
P-glycoprotein inhibitor INon-inhibitor0.8922
P-glycoprotein inhibitor IINon-inhibitor0.8607
Renal organic cation transporterNon-inhibitor0.9695
CYP450 2C9 substrateNon-substrate0.7048
CYP450 2D6 substrateNon-substrate0.8347
CYP450 3A4 substrateNon-substrate0.5571
CYP450 1A2 substrateNon-inhibitor0.8481
CYP450 2C9 inhibitorNon-inhibitor0.8427
CYP450 2D6 inhibitorNon-inhibitor0.913
CYP450 2C19 inhibitorNon-inhibitor0.8219
CYP450 3A4 inhibitorNon-inhibitor0.8176
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9624
Ames testNon AMES toxic0.8363
CarcinogenicityNon-carcinogens0.6271
BiodegradationNot ready biodegradable0.8103
Rat acute toxicity1.8514 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9997
hERG inhibition (predictor II)Non-inhibitor0.8314
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Bristol laboratories inc div bristol myers co
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point190 °CPhysProp
logP1.3Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.512 mg/mLALOGPS
logP0.85ALOGPS
logP-0.015ChemAxon
logS-2.9ALOGPS
pKa (Strongest Acidic)3.63ChemAxon
pKa (Strongest Basic)5.47ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area89.95 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity99.9 m3·mol-1ChemAxon
Polarizability39.58 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis 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].
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassLactams
Sub ClassBeta lactams
Direct ParentPenicillins
Alternative Parents
Substituents
  • Penicillin
  • Phenylimidazolidine
  • Alpha-amino acid or derivatives
  • Benzenoid
  • Imidazolidinone
  • Monocyclic benzene moiety
  • Thiazolidine
  • Tertiary carboxylic acid amide
  • Imidazolidine
  • Tertiary amine
  • Carboxamide group
  • Azetidine
  • Azacycle
  • Dialkylthioether
  • Hemithioaminal
  • Thioether
  • Secondary amine
  • Monocarboxylic acid or derivatives
  • Secondary aliphatic amine
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors

Targets

Kind
Protein
Organism
Streptococcus pneumoniae (strain ATCC BAA-255 / R6)
Pharmacological action
yes
Actions
inhibitor
General Function:
Transferase activity, transferring acyl groups
Specific Function:
Not Available
Gene Name:
pbp2a
Uniprot ID:
Q8DNB6
Molecular Weight:
80797.94 Da
References
  1. Neu HC: Aminopenicillins - clinical pharmacology and use in disease states. Int J Clin Pharmacol Biopharm. 1975 Mar;11(2):132-44. [PubMed:1095502 ]
  2. 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 (strain ATCC BAA-255 / R6)
Pharmacological action
yes
Actions
inhibitor
General Function:
Transferase activity, transferring acyl groups
Specific Function:
Not Available
Gene Name:
pbp1b
Uniprot ID:
Q7CRA4
Molecular Weight:
89479.92 Da
References
  1. Neu HC: Aminopenicillins - clinical pharmacology and use in disease states. Int J Clin Pharmacol Biopharm. 1975 Mar;11(2):132-44. [PubMed:1095502 ]
  2. 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
Molecular Weight:
45209.84 Da
References
  1. Neu HC: Aminopenicillins - clinical pharmacology and use in disease states. Int J Clin Pharmacol Biopharm. 1975 Mar;11(2):132-44. [PubMed:1095502 ]
  2. 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 (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
Molecular Weight:
79700.9 Da
References
  1. Neu HC: Aminopenicillins - clinical pharmacology and use in disease states. Int J Clin Pharmacol Biopharm. 1975 Mar;11(2):132-44. [PubMed:1095502 ]
  2. 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 (strain ATCC BAA-255 / R6)
Pharmacological action
yes
Actions
inhibitor
General Function:
Penicillin binding
Specific Function:
Not Available
Gene Name:
penA
Uniprot ID:
P0A3M6
Molecular Weight:
73872.305 Da
References
  1. Neu HC: Aminopenicillins - clinical pharmacology and use in disease states. Int J Clin Pharmacol Biopharm. 1975 Mar;11(2):132-44. [PubMed:1095502 ]
  2. 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 ]
Comments
comments powered by Disqus
Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23