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Identification
NameAnisindione
Accession NumberDB01125  (APRD00799)
Typesmall molecule
Groupsapproved
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
SynonymLanguageCode
Anisin indandioneNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
MiradonNot Available
UnidoneNot Available
Brand mixturesNot Available
CategoriesNot Available
CAS number117-37-3
WeightAverage: 252.2647
Monoisotopic: 252.07864425
Chemical FormulaC16H12O3
InChI KeyInChIKey=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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassPhenylpropanoids and Polyketides
ClassStilbenes
SubclassNot Available
Direct parentStilbenes
Alternative parentsIndanones; Anisoles; Alkyl Aryl Ethers; Ketones; Polyamines
Substituentsindanone; indane; phenol ether; anisole; alkyl aryl ether; benzene; ketone; ether; polyamine; carbonyl group
Classification descriptionThis compound belongs to the stilbenes. These are organic compounds containing a 1,2-diphenylethylene moiety. Stilbenes (C6-C2-C6 ) are derived from the common phenylpropene (C6-C3) skeleton building block. The introduction of one or more hydroxyl groups to a phenyl ring lead to stilbenoids.
Pharmacology
IndicationFor 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.
PharmacodynamicsAnisindione 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 actionLike 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.
AbsorptionAccumulation does not occur with repeated dosing.
Volume of distributionNot Available
Protein bindingNot Known
Metabolism
Route of eliminationNot Available
Half lifeNot Known
ClearanceNot Available
ToxicityAn 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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 1.0
Blood Brain Barrier + 0.9051
Caco-2 permeable + 0.8206
P-glycoprotein substrate Non-substrate 0.6289
P-glycoprotein inhibitor I Inhibitor 0.5099
P-glycoprotein inhibitor II Non-inhibitor 0.534
Renal organic cation transporter Non-inhibitor 0.8467
CYP450 2C9 substrate Non-substrate 0.7584
CYP450 2D6 substrate Non-substrate 0.8872
CYP450 3A4 substrate Non-substrate 0.5965
CYP450 1A2 substrate Inhibitor 0.9594
CYP450 2C9 substrate Inhibitor 0.8996
CYP450 2D6 substrate Non-inhibitor 0.9457
CYP450 2C19 substrate Inhibitor 0.6234
CYP450 3A4 substrate Non-inhibitor 0.8639
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.6618
Ames test AMES toxic 0.6006
Carcinogenicity Non-carcinogens 0.8733
Biodegradation Not ready biodegradable 0.8575
Rat acute toxicity 2.4052 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.944
hERG inhibition (predictor II) Non-inhibitor 0.8898
Pharmacoeconomics
Manufacturers
  • Schering corp sub schering plough corp
PackagersNot Available
Dosage forms
FormRouteStrength
TabletOral
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point155-156Sperber, 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 solubility1.28e-02 g/lALOGPS
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 area43.37ChemAxon
rotatable bond count2ChemAxon
refractivity71.7ChemAxon
polarizability26.3ChemAxon
number of rings3ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

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

General Reference
  1. CONNELL WF, MAYER GA: Evaluation of anticoagulant therapy with anisindione (miradon). Can Med Assoc J. 1959 May 15;80(10):785-90. Pubmed
External Links
ResourceLink
PubChem Compound2197
PubChem Substance46504660
ChemSpider2112
ChEBI133809
ChEMBLCHEMBL712
Therapeutic Targets DatabaseDAP001274
PharmGKBPA164746467
RxListhttp://www.rxlist.com/cgi/generic/miradon.htm
Drugs.comhttp://www.drugs.com/pdr/anisindione.html
PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/mir1623.shtml
WikipediaAnisindione
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AcetaminophenAcetaminophen increases the anticoagulant effect of anisindione. Monitor for changes in the therapeutic and adverse effects of anisindione if acetaminophen is initiated, discontinued or dose changed.
Acetylsalicylic acidAcetylsalicylic acid increases effect of the anticoagulant, anisindione.
AllopurinolAllopurinol may increase the anticoagulant effect of anisindione.
AminoglutethimideAminoglutethimide may decrease the anticoagulant effect of anisindione.
AmiodaroneAmiodarone may increase the anticoagulant effect of anisindione.
AmprenavirAmprenavir may increase the anticoagulant effect of anisindione by increasing its serum concentration.
AprepitantAprepitant may decrease the anticoagulant effect of anisindione by decreasing its serum concentration.
AtazanavirThe protease inhibitor, atazanavir, may increase the anticoagulant effect of anisindione.
AzathioprineAzathioprine may decrease the anticoagulant effect of anisindione.
AzithromycinAzithromycin may increase the anticoagulant effect of anisindione by increasing its serum concentration.
BetamethasoneThe corticosteroid, betamethasone, alters the anticoagulant effect of anisindione.
BosentanBosentan may decrease the anticoagulant effect of anisindione by increasing its metabolism.
CapecitabineCapecitabine may increase the anticoagulant effect of anisindione by increasing its serum concentration.
CarbamazepineCarbamazepine may decrease the anticoagulant effect of anisindione by decreasing its serum concentration.
CefotetanThe cephalosporin, cefotetan, may increase the anticoagulant effect of anisindione.
CefoxitinThe cephalosporin, cefoxitin, may increase the anticoagulant effect of anisindione.
CeftriaxoneThe cephalosporin, ceftriaxone, may increase the anticoagulant effect of anisindione.
CelecoxibCelecoxib may increase the anticoagulant effect of anisindione.
CholestyramineThe bile acid sequestrant, cholestyramine, may decrease the anticoagulant effect of anisindione by decreasing its absorption.
CimetidineCimetidine may increase the anticoagulant effect of anisindione.
CiprofloxacinThe quinolone antibiotic, ciprofloxacin, may increase the anticoagulant effect of anisindione.
CisaprideCisapride may increase the anticoagulant effect of anisindione.
CitalopramThe SSRI, citalopram, increases the effect of anticoagulant, anisindione.
ClarithromycinThe macrolide, clarithromycin, may increase the anticoagulant effect of anisindione.
ClofibrateThe fibrate increases the anticoagulant effect
ColestipolThe bile acid sequestrant, colestipol, may decrease the anticoagulant effect of anisindione by decreasing its absorption.
CyclophosphamideThe antineoplastic agent, cyclophosphamide may alter the anticoagulant effect of anisindione.
DanazolThe androgen, danazol, may increase the anticoagulant effect of anisindione.
DemeclocyclineThe tetracycline, demeclocycline, may increase the anticoagulant effect of anisindione.
DexamethasoneThe corticosteroid, dexamethasone, alters the anticoagulant effect of anisindione.
DextropropoxyphenePropoxyphene may increase the anticoagulant effect of anisindione.
DextrothyroxineThe thyroid hormone, dextrothyroxine, increase the anticoagulant effect of anisindione.
DiclofenacThe NSAID, diclofenac, may increase the anticoagulant effect of anisindione.
DicloxacillinDicloxacillin may decrease the anticoagulant effect of anisindione.
DiflunisalThe NSAID, diflunisal, may increase the anticoagulant effect of anisindione.
DisulfiramDisulfiram may increase the anticoagulant effect of anisindione.
DoxycyclineThe tetracycline, doxycycline, may increase the anticoagulant effect of anisindione.
ErythromycinThe macrolide, erythromycin, may increase the anticoagulant effect of anisindione.
EthchlorvynolEthchlorvynol may decrease the anticoagulant effect of anisindione.
Ethinyl EstradiolIncreased thrombotic risk due to estrogen
EtodolacThe NSAID, etodolac, may increase the anticoagulant effect of anisindione.
EtoricoxibEtoricoxib may increase the anticoagulant effect of anisindione.
FenofibrateFenofibrate may increase the anticoagulant effect of anisindione.
FenoprofenThe NSAID, fenoprofen, may increase the anticoagulant effect of anisindione.
FluconazoleFluconazole may increase the serum concentration of anisindione by decreasing its metabolism.
FludrocortisoneThe corticosteroid, fludrocortisone, alters the anticoagulant effect of anisindione.
FluorouracilThe antineoplasic agent, fluorouracil, may increase the anticoagulant effect of anisindione.
FluoxetineThe SSRI, fluoxetine, increases the effect of anticoagulant, anisindione.
FluoxymesteroneThe androgen, fluoxymesterone, may increase the anticoagulant effect of anisindione.
FlurbiprofenThe NSAID, flurbiprofen, may increase the anticoagulant effect anisindione.
FluvastatinFluvastatin may increase the anticoagulant effect of anisindione. Monitor for changes in the therapeutic and adverse effects of anisindione if fluvastatin if initiated, discontinued or dose changed.
FluvoxamineFluvoxamine may increase the anticoagulant effect of anisindione by increasing its serum concentration.
FosamprenavirThe protease inhibitor, fosamprenavir, may increase the anticoagulant effect of anisindione.
FosphenytoinIncreased hydantoin levels and risk of bleeding
GefitinibGefitinib may increase the anticoagulant effect of anisindione.
GemcitabineGemcitabine may increase the anticoagulant effect of anisindione.
GemfibrozilGemfibrozil may increase the anticoagulant effect of anisindione.
GlutethimideGlutethimide may decrease the anticoagulant effect of anisindione.
GriseofulvinGriseofulvin may decrease the anticoagulant effect of anisindione.
HydrocortisoneThe corticosteroid, hydrocortisone, alters the anticoagulant effect of anisindione.
IbuprofenThe NSAID, ibuprofen, may increase the anticoagulant effect of anisindione.
ImatinibImatinib may increase the anticoagulant effect of anisindione.
IndinavirThe protease inhibitor, indinavir, may increase the anticoagulant effect of anisindione.
IndomethacinThe NSAID, indomethacin, may increase the anticoagulant effect of anisindione.
IsoniazidIsoniazid may increase the anticoagulant effect of anisindione.
ItraconazoleItraconazole may increase the anticoagulant effect of anisindione.
KetoconazoleKetoconazole may increase the anticoagulant effect of anisindione.
KetoprofenThe NSAID, ketoprofen, may increase the anticoagulant effect of anisindione.
KetorolacThe NSAID, ketorolac, may increase the anticoagulant effect of anisindione.
LeflunomideLeflunomide may increase the anticoagulant effect of anisindione.
LevamisoleLevamisole may increase the anticoagulant effect of anisindione.
LevofloxacinThe quinolone antibiotic, levofloxacin, may increase the anticoagulant effect of anisindione.
LevothyroxineThe thyroid hormone, levothyroxine, increase the anticoagulant effect of anisindione.
LovastatinLovastatin may increase the anticoagulant effect of anisindione. Monitor for changes in the therapeutic and adverse effects of anisindione if lovastatin if initiated, discontinued or dose changed.
LumiracoxibLumiracoxib may increase the anticoagulant effect of anisindione.
Medroxyprogesterone AcetateMedroxyprogesterone may increase the anticoagulant effect of anisindione.
Mefenamic acidThe NSAID, mefanamic acid, may increase the anticoagulant effect of anisindione.
MefloquineMefloquine may increase the anticoagulant effect of anisindione.
MeloxicamMeloxicam may increase the anticoagulant effect of anisindione.
MercaptopurineMercaptopurine may decrease the anticoagulant effect of anisindione.
MethimazoleThe antithyroid agent, methimazole, may decrease the anticoagulant effect of anisindione.
MetronidazoleMetronidazole may increase the anticoagulant effect of anisindione.
MiconazoleMiconazole may increase the serum concentration of anisindione by decreasing its metabolism.
MinocyclineThe tetracycline, minocycline, may increase the anticoagulant effect of anisindione.
MitotaneMitotane may decrease the anticoagulant effect of anisindione.
MoxifloxacinThe quinolone antibiotic, moxifloxacin, may increase the anticoagulant effect of anisindione.
NabumetoneThe NSAID, nabumetone, may increase the anticoagulant effect anisindione.
Nalidixic AcidThe quinolone antibiotic, nalidixic acid, may increase the anticoagulant effect of anisindione.
NaproxenThe NSAID, naproxen, may increase the anticoagulant effect of anisindione.
NelfinavirThe protease inhibitor, nelfinavir, may increase the anticoagulant effect of anisindione.
NevirapineNevirapine may decrease the anticoagulant effect of anisindione.
NorfloxacinThe quinolone antibiotic, norfloxacin, may increase the anticoagulant effect of anisindione.
OfloxacinThe quinolone antibiotic, ofloxacin, may increase the anticoagulant effect of anisindione.
OrlistatOrlistat may increase the anticoagulant effect of anisindione.
OxaprozinThe NSAID, oxaprozin, may increase the anticoagulant effect of anisinodione.
OxyphenbutazoneThe NSAID, oxyphenbutazone, may increase the anticoagulant effect of anisindione.
ParoxetineThe SSRI, paroxetine, increases the effect of the anticoagulant, anisindione.
PentoxifyllinePentoxifylline may increase the anticoagulant effect of anisindione.
PhenobarbitalThe barbiturate, phenobarbital, decreases the anticoagulant effect of anisindione.
PhenylbutazoneThe NSAID, phenylbutazone, may increase the anticoagulant effect of anisindione.
PhenytoinIncreased hydantoin levels and risk of bleeding
PiroxicamThe NSAID, piroxicam, may increase the anticoagulant effect of anisindione.
PrednisoloneThe corticosteroid, prednisolone, alters the anticoagulant effect of anisindione.
PrednisoneThe corticosteroid, prednisone, alters the anticoagulant effect of anisindione.
PrimidoneThe barbiturate, primidone, decreases the anticoagulant effect of anisindione.
PropafenonePropafenone may increase the anticoagulant effect of anisindione.
PropylthiouracilThe anti-thyroid agent, propylthiouracil, may decrease the anticoagulant effect of anisindione.
QuinidineQuinidine may increase the anticoagulant effect of anisindione.
QuinineQuinine may increase the anticoagulant effect of anisindione.
RanitidineRanitidine may increase the anticoagulant effect of anisindione. (Conflicting evidence)
RifabutinRifabutin, may decrease the anticoagulant effect of anisindione.
RifampicinRifampin may decrease the anticoagulant effect of anisindione.
TelithromycinTelithromycin may increase the anticoagulant effect of anisindione.
TenoxicamThe NSAID, tenoxicam, may increase the anticoagulant effect of anisindione.
TestosteroneThe androgen may increase the anticoagulant effect of anisindione.
TetracyclineTetracycline may increase the anticoagulant effect of anisindione.
TigecyclineTigecycline may increase the anticoagulant effect of anisindione.
TriamcinoloneThe corticosteroid, triamcinolone, alters the anticoagulant effect of anisindione.
Food InteractionsNot Available

1. Vitamin K-dependent gamma-carboxylase

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Vitamin K-dependent gamma-carboxylase P38435 Details

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
  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
  3. Anisindione – Basic Profile / Key Facts. Source
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

Comments
Drug created on June 13, 2005 07:24 / Updated on March 28, 2014 10:09