Identification

Name
Anisindione
Accession Number
DB01125  (APRD00799)
Type
Small Molecule
Groups
Approved
Description

Anisindione is a synthetic anticoagulant and an indanedione derivative. It prevents the formation of active procoagulation factors II, VII, IX, and X, as well as the anticoagulant proteins C and S, in the liver by inhibiting the vitamin K-mediated gamma-carboxylation of precursor proteins.

Structure
Thumb
Synonyms
  • 2-(4-Methoxyphenyl)-1H-indene-1,3(2H)-dione
  • 2-(4-Methoxyphenyl)indan-1,3-dione
  • 2-(P-Methoxyphenyl)-1,3-indandione
  • 2-(P-Methoxyphenyl)indane-1,3-dione
  • 2-P-Anisyl-1,3-indandione
  • 2-Para-anisyl-1,3-indandione
  • Anisin indandione
  • Anisindiona
  • Anisindionum
International/Other Brands
Miradon / Unidone
Categories
UNII
S747T1ERAJ
CAS number
117-37-3
Weight
Average: 252.2647
Monoisotopic: 252.07864425
Chemical Formula
C16H12O3
InChI Key
XRCFXMGQEVUZFC-UHFFFAOYSA-N
InChI
InChI=1S/C16H12O3/c1-19-11-8-6-10(7-9-11)14-15(17)12-4-2-3-5-13(12)16(14)18/h2-9,14H,1H3
IUPAC Name
2-(4-methoxyphenyl)-2,3-dihydro-1H-indene-1,3-dione
SMILES
COC1=CC=C(C=C1)C1C(=O)C2=CC=CC=C2C1=O

Pharmacology

Indication

For the prophylaxis and treatment of venous thrombosis and its extension, the treatment of atrial fibrillation with embolization, the prophylaxis and treatment of pulmonary embolism, and as an adjunct in the treatment of coronary occlusion.

Structured Indications
Not Available
Pharmacodynamics

Anisindione is a synthetic anticoagulant and an indanedione derivative. It is prescribed only if you cannot take coumarin-type anticoagulants such as coumadin as anisindione is a powerful drug with serious potential side effects. Anticoagulants decrease the clotting ability of the blood and therefore help to prevent harmful clots from forming in the blood vessels. These medicines are sometimes called blood thinners, although they do not actually thin the blood. They also will not dissolve clots that already have formed, but they may prevent the clots from becoming larger and causing more serious problems.

Mechanism of action

Like phenindione, to which it is related chemically, anisindione exercises its therapeutic action by reducing the prothrombin activity of the blood. Anisindione prevents the formation of active procoagulation factors II, VII, IX, and X, as well as the anticoagulant proteins C and S, in the liver by inhibiting the vitamin K–mediated gamma-carboxylation of precursor proteins. Anisindione has no direct thrombolytic effect and does not reverse ischemic tissue damage, although it may limit extension of existing thrombi and prevent secondary thromboembolic complications.

TargetActionsOrganism
AVitamin K-dependent gamma-carboxylase
inhibitor
Human
Absorption

Accumulation does not occur with repeated dosing.

Volume of distribution
Not Available
Protein binding

Not Known

Metabolism
Not Available
Route of elimination
Not Available
Half life

Not Known

Clearance
Not Available
Toxicity

An overdose is likely to cause abnormal bleeding, for which the symptoms include: bleeding from gums or nose, blood in urine or stools, excessive bleeding from minor cuts, patches of discoloration or bruises on the skin.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

Synthesis Reference

Sperber, N.; US. Patent 2,899,358; August 11, 1959; assigned to Schering Corporation

General References
  1. CONNELL WF, MAYER GA: Evaluation of anticoagulant therapy with anisindione (miradon). Can Med Assoc J. 1959 May 15;80(10):785-90. [PubMed:13652026]
External Links
Human Metabolome Database
HMDB15257
PubChem Compound
2197
PubChem Substance
46504660
ChemSpider
2112
BindingDB
50280155
ChEBI
133809
ChEMBL
CHEMBL712
Therapeutic Targets Database
DAP001274
PharmGKB
PA164746467
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Anisindione

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)155-156Sperber, N.; US. Patent 2,899,358; August 11, 1959; assigned to Schering Corporation
water solubility79.8 mg/LNot Available
logP2.88SANGSTER (1993)
Predicted Properties
PropertyValueSource
Water Solubility0.0128 mg/mLALOGPS
logP2.99ALOGPS
logP2.72ChemAxon
logS-4.3ALOGPS
pKa (Strongest Acidic)4.5ChemAxon
pKa (Strongest Basic)-4.8ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area43.37 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity71.7 m3·mol-1ChemAxon
Polarizability26.3 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9051
Caco-2 permeable+0.8206
P-glycoprotein substrateNon-substrate0.6289
P-glycoprotein inhibitor IInhibitor0.5099
P-glycoprotein inhibitor IINon-inhibitor0.534
Renal organic cation transporterNon-inhibitor0.8467
CYP450 2C9 substrateNon-substrate0.7584
CYP450 2D6 substrateNon-substrate0.8872
CYP450 3A4 substrateNon-substrate0.5965
CYP450 1A2 substrateInhibitor0.9594
CYP450 2C9 inhibitorInhibitor0.8996
CYP450 2D6 inhibitorNon-inhibitor0.9457
CYP450 2C19 inhibitorInhibitor0.6234
CYP450 3A4 inhibitorNon-inhibitor0.8639
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6618
Ames testAMES toxic0.6006
CarcinogenicityNon-carcinogens0.8733
BiodegradationNot ready biodegradable0.8575
Rat acute toxicity2.4052 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.944
hERG inhibition (predictor II)Non-inhibitor0.8898
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 indanediones. These are compounds containing an indane ring bearing two ketone groups.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Indanes
Sub Class
Indanones
Direct Parent
Indanediones
Alternative Parents
Phenoxy compounds / Methoxybenzenes / Aryl alkyl ketones / Anisoles / Beta-diketones / Alkyl aryl ethers / Organic oxides / Hydrocarbon derivatives
Substituents
Indanedione / Phenoxy compound / Anisole / Methoxybenzene / Aryl alkyl ketone / Aryl ketone / Phenol ether / Alkyl aryl ether / 1,3-diketone / Monocyclic benzene moiety
Molecular Framework
Aromatic homopolycyclic compounds
External Descriptors
aromatic ketone, beta-diketone (CHEBI:133809)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Gamma-glutamyl carboxylase activity
Specific Function
Mediates the vitamin K-dependent carboxylation of glutamate residues to calcium-binding gamma-carboxyglutamate (Gla) residues with the concomitant conversion of the reduced hydroquinone form of vit...
Gene Name
GGCX
Uniprot ID
P38435
Uniprot Name
Vitamin K-dependent gamma-carboxylase
Molecular Weight
87560.065 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]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  4. Source [Link]

Drug created on June 13, 2005 07:24 / Updated on November 07, 2017 01:47