Identification

Name
Hetacillin
Accession Number
DB00739  (APRD01012)
Type
Small Molecule
Groups
Approved, Vet approved, Withdrawn
Description

Hetacillin 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 Hetacillin has been withdrawn from the market since it has been discovered that it has no therapeutic advantage compared to non-ester derivatives like ampicillin.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 IDs
BL-P 804 / BL-P-804 / BRL 804 / BRL-804
Product Ingredients
IngredientUNIICASInChI Key
Hetacillin potassium95PFX5932Y5321-32-4QRSPJBLLJXVPDD-XFAPPKAWSA-M
International/Other Brands
Natacillin (Bristol-Myers Squibb) / Versapen (Bristol-Myers Squibb)
Categories
UNII
TN4JSC48CV
CAS number
3511-16-8
Weight
Average: 389.469
Monoisotopic: 389.140926929
Chemical Formula
C19H23N3O4S
InChI Key
DXVUYOAEDJXBPY-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)[C@H]2N1C(=O)[C@H](NC1(C)C)C1=CC=CC=C1)C(O)=O

Pharmacology

Indication

Hetacillin is a beta-lactam antibiotic prodrug used to treat bacterial infections. In the body it gets converted to ampicillin.

Pharmacodynamics

Hetacillin 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 action

Hetacillin 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.

TargetActionsOrganism
APenicillin-binding protein 2a
inhibitor
Streptococcus pneumoniae (strain ATCC BAA-255 / R6)
APenicillin-binding protein 1b
inhibitor
Streptococcus pneumoniae (strain ATCC BAA-255 / R6)
APenicillin-binding protein 3
inhibitor
Streptococcus pneumoniae
APenicillin-binding protein 1A
inhibitor
Streptococcus pneumoniae (strain ATCC BAA-255 / R6)
APenicillin-binding protein 2B
inhibitor
Streptococcus pneumoniae (strain ATCC BAA-255 / R6)
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Hydrolyzed to active ampicillin via esterases

Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Enteric bacteria and other eubacteria
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
ClomocyclineThe therapeutic efficacy of Hetacillin can be decreased when used in combination with Clomocycline.
DemeclocyclineThe therapeutic efficacy of Hetacillin can be decreased when used in combination with Demeclocycline.
DoxycyclineThe therapeutic efficacy of Hetacillin can be decreased when used in combination with Doxycycline.
LymecyclineThe therapeutic efficacy of Hetacillin can be decreased when used in combination with Lymecycline.
MethacyclineThe therapeutic efficacy of Hetacillin can be decreased when used in combination with Methacycline.
MinocyclineThe therapeutic efficacy of Hetacillin can be decreased when used in combination with Minocycline.
OxytetracyclineThe therapeutic efficacy of Hetacillin can be decreased when used in combination with Oxytetracycline.
PenimepicyclineThe therapeutic efficacy of Hetacillin can be decreased when used in combination with Penimepicycline.
RolitetracyclineThe therapeutic efficacy of Hetacillin can be decreased when used in combination with Rolitetracycline.
SarecyclineThe therapeutic efficacy of Hetacillin can be decreased when used in combination with Sarecycline.
Food Interactions
Not Available

References

Synthesis Reference

U.S. Patent 3,198,804.

General References
Not Available
External Links
Human Metabolome Database
HMDB0014877
KEGG Drug
D01074
KEGG Compound
C11729
PubChem Compound
443387
PubChem Substance
46504545
ChemSpider
391616
ChEBI
5683
ChEMBL
CHEMBL1201116
Therapeutic Targets Database
DAP001167
PharmGKB
PA164746559
Wikipedia
Hetacillin
ATC Codes
J01CA18 — Hetacillin

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
  • Bristol laboratories inc div bristol myers co
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)190 °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 FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

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
Phenylimidazolidines / Alpha amino acids and derivatives / Imidazolidinones / Benzene and substituted derivatives / Thiazolidines / Tertiary carboxylic acid amides / Amino acids / Azetidines / Thiohemiaminal derivatives / Monocarboxylic acids and derivatives
show 8 more
Substituents
Penicillin / Phenylimidazolidine / Alpha-amino acid or derivatives / Monocyclic benzene moiety / Imidazolidinone / Benzenoid / Imidazolidine / Thiazolidine / Tertiary carboxylic acid amide / Amino acid or derivatives
show 22 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
penicillin (CHEBI:5683)

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
Uniprot Name
Penicillin-binding protein 2a
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
Uniprot Name
Penicillin-binding protein 1b
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
Uniprot Name
Penicillin-binding protein 3
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
Uniprot Name
Penicillin-binding protein 1A
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
Not Available
Specific Function
Penicillin binding
Gene Name
penA
Uniprot ID
P0A3M6
Uniprot Name
Penicillin-binding protein 2B
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]

Drug created on June 13, 2005 07:24 / Updated on October 01, 2018 16:31