Enoximone

Identification

Summary

Enoximone is a selective phosphodiesterase inhibitor indicated in the short term treatment of congestive heart failure.

Generic Name
Enoximone
DrugBank Accession Number
DB04880
Background

Enoximone is a selective phosphodiesterase inhibitor with vasodilating and positive inotropic activity that does not cause changes in myocardial oxygen consumption. It is used in patients with congestive heart failure. Trials were halted in the U.S., but the drug is used in various countries.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 248.301
Monoisotopic: 248.061948328
Chemical Formula
C12H12N2O2S
Synonyms
  • Enoximona
  • Enoximone
  • Enoximonum
External IDs
  • MDL 17,043
  • MDL-17043

Pharmacology

Indication

For the treatment of congestive heart failure.

Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofCongestive heart failure (chf)•••••••••••••••••••••• •••••••••• ••••••••
Treatment ofCongestive heart failure (chf)•••••••••••••••••••••• •••••••••• ••••••••
Contraindications & Blackbox Warnings
Prevent Adverse Drug Events Today
Tap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events with our Clinical API
Learn more
Pharmacodynamics

Enoximone is a phosphodiesterase inhibitor (type III) that increases the force of contraction of the heart and dilates blood vessels. In June 2005, Myogen announced that they were discontinuing development of enoximone due to negative results. The drug is approved for use in the UK.

Mechanism of action

Further research is required to determine accurately the mechanism of action of drugs with phosphodiesterase inhibitory activity, however, inhibition of PDE3 inhibits degredation of cGMP. This allows for increased NO release and vascular relaxation.

TargetActionsOrganism
AcGMP-inhibited 3',5'-cyclic phosphodiesterase A
inhibitor
Humans
Absorption

Bioavailabvility is 50% following oral administration.

Volume of distribution

Not Available

Protein binding

85%

Metabolism

Hepatic oxidation

Route of elimination

Not Available

Half-life

4-10 hours

Clearance

Not Available

Adverse Effects
Improve decision support & research outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!
See the data
Improve decision support & research outcomes with our structured adverse effects data.
See a data sample
Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AmrinoneThe risk or severity of congestive heart failure, bleeding, hypotension, and Tachycardia can be increased when Amrinone is combined with Enoximone.
AnagrelideThe risk or severity of congestive heart failure, bleeding, hypotension, and Tachycardia can be increased when Anagrelide is combined with Enoximone.
CilostazolThe risk or severity of congestive heart failure, bleeding, hypotension, and Tachycardia can be increased when Cilostazol is combined with Enoximone.
IloprostIloprost may increase the hypotensive activities of Enoximone.
Isosorbide mononitrateEnoximone may increase the vasodilatory activities of Isosorbide mononitrate.
Food Interactions
Not Available

Products

Drug product information from 10+ global regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
International/Other Brands
Perfan

Categories

ATC Codes
C01CE03 — Enoximone
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as aryl-phenylketones. These are aromatic compounds containing a ketone substituted by one aryl group, and a phenyl group.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Carbonyl compounds
Direct Parent
Aryl-phenylketones
Alternative Parents
Thiophenol ethers / Benzoyl derivatives / Carbonylimidazoles / Alkylarylthioethers / Vinylogous amides / Heteroaromatic compounds / Ureas / Sulfenyl compounds / Azacyclic compounds / Organopnictogen compounds
show 3 more
Substituents
Alkylarylthioether / Aromatic heteromonocyclic compound / Aryl thioether / Aryl-phenylketone / Azacycle / Azole / Benzenoid / Benzoyl / Heteroaromatic compound / Hydrocarbon derivative
show 14 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
C7Z4ITI7L7
CAS number
77671-31-9
InChI Key
ZJKNESGOIKRXQY-UHFFFAOYSA-N
InChI
InChI=1S/C12H12N2O2S/c1-7-10(14-12(16)13-7)11(15)8-3-5-9(17-2)6-4-8/h3-6H,1-2H3,(H2,13,14,16)
IUPAC Name
4-methyl-5-[4-(methylsulfanyl)benzoyl]-2,3-dihydro-1H-imidazol-2-one
SMILES
CSC1=CC=C(C=C1)C(=O)C1=C(C)NC(=O)N1

References

General References
  1. Sandroni C, Cavallaro F, Caricato A, Scapigliati A, Fenici P, Antonelli M: Enoximone in cardiac arrest caused by propranolol: two case reports. Acta Anaesthesiol Scand. 2006 Jul;50(6):759-61. [Article]
  2. van der Maaten JM, de Vries AJ, Rietman GW, Gallandat Huet RC, De Hert SG: Effects of preemptive enoximone on left ventricular diastolic function after valve replacement for aortic stenosis. J Cardiothorac Vasc Anesth. 2007 Jun;21(3):357-66. Epub 2006 May 4. [Article]
  3. Schauvliege S, Van den Eede A, Duchateau L, Gasthuys F: Cardiovascular effects of enoximone in isoflurane anaesthetized ponies. Vet Anaesth Analg. 2007 Nov;34(6):416-30. Epub 2007 Aug 13. [Article]
  4. Boldt J, Suttner S: Combined use of ultra-short acting beta-blocker esmolol and intravenous phosphodiesterase 3 inhibitor enoximone. Expert Opin Pharmacother. 2007 Sep;8(13):2135-47. [Article]
Human Metabolome Database
HMDB0015599
KEGG Drug
D04004
PubChem Compound
53708
PubChem Substance
46505575
ChemSpider
48492
BindingDB
50241379
RxNav
49626
ChEBI
135010
ChEMBL
CHEMBL249856
ZINC
ZINC000009225358
Therapeutic Targets Database
DAP000611
PharmGKB
PA164768794
Wikipedia
Enoximone

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4TerminatedTreatmentEnoximone / Exacerbation of COPD / Phosphodiesterase Inhibitor1
4Unknown StatusTreatmentMicrocirculation / Severe Sepsis1
3CompletedTreatmentCoronary Artery Disease (CAD)1
3TerminatedTreatmentCongestive Heart Failure (CHF)2

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, solution, concentrateIntravenous; Parenteral100 MG/20ML
Solution, concentrateIntravenous125 mg
Solution, concentrateIntravenous50 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)256 dec °CPhysProp
Predicted Properties
PropertyValueSource
Water Solubility0.0682 mg/mLALOGPS
logP1.97ALOGPS
logP1.84Chemaxon
logS-3.6ALOGPS
pKa (Strongest Acidic)9.68Chemaxon
pKa (Strongest Basic)-7.8Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count2Chemaxon
Hydrogen Donor Count2Chemaxon
Polar Surface Area58.2 Å2Chemaxon
Rotatable Bond Count3Chemaxon
Refractivity70.04 m3·mol-1Chemaxon
Polarizability25.67 Å3Chemaxon
Number of Rings2Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9659
Blood Brain Barrier+0.77
Caco-2 permeable-0.5178
P-glycoprotein substrateNon-substrate0.6512
P-glycoprotein inhibitor INon-inhibitor0.9333
P-glycoprotein inhibitor IINon-inhibitor0.992
Renal organic cation transporterNon-inhibitor0.892
CYP450 2C9 substrateNon-substrate0.6586
CYP450 2D6 substrateNon-substrate0.7445
CYP450 3A4 substrateNon-substrate0.6998
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9431
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorInhibitor0.5842
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8173
Ames testNon AMES toxic0.7916
CarcinogenicityNon-carcinogens0.9418
BiodegradationNot ready biodegradable0.9737
Rat acute toxicity2.0807 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9554
hERG inhibition (predictor II)Non-inhibitor0.8438
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-MSsplash10-0udi-4940000000-2c3d1d1ddd2652a0e57c
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-004i-3910100000-ff2ed6a9d4b5b2530185
MS/MS Spectrum - , positiveLC-MS/MSsplash10-004i-3910100000-ff2ed6a9d4b5b2530185
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0002-0090000000-1e4859899bdc08af7c6c
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-001i-0950000000-760710ff1fa6484f80c0
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0pc0-0940000000-005b029a502c3051fb0c
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-002f-9720000000-31420555d3eee037a3a9
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0ab9-3900000000-fa4b06c4bf9e2b2fa039
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-000x-7900000000-a63b34b588039a4b1e20
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-167.3236816
predicted
DarkChem Lite v0.1.0
[M-H]-167.9913816
predicted
DarkChem Lite v0.1.0
[M-H]-157.84827
predicted
DeepCCS 1.0 (2019)
[M+H]+168.8255816
predicted
DarkChem Lite v0.1.0
[M+H]+168.6492816
predicted
DarkChem Lite v0.1.0
[M+H]+160.20625
predicted
DeepCCS 1.0 (2019)
[M+Na]+167.7570816
predicted
DarkChem Lite v0.1.0
[M+Na]+166.29942
predicted
DeepCCS 1.0 (2019)

Targets

Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
Learn more
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Metal ion binding
Specific Function
Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes.
Gene Name
PDE3A
Uniprot ID
Q14432
Uniprot Name
cGMP-inhibited 3',5'-cyclic phosphodiesterase A
Molecular Weight
124978.06 Da
References
  1. Boldt J, Suttner S: Combined use of ultra-short acting beta-blocker esmolol and intravenous phosphodiesterase 3 inhibitor enoximone. Expert Opin Pharmacother. 2007 Sep;8(13):2135-47. [Article]
  2. Sandroni C, Cavallaro F, Caricato A, Scapigliati A, Fenici P, Antonelli M: Enoximone in cardiac arrest caused by propranolol: two case reports. Acta Anaesthesiol Scand. 2006 Jul;50(6):759-61. [Article]

Drug created at October 20, 2007 19:43 / Updated at June 19, 2021 00:26