Dicoumarol

Synonyms :
3,3′-Methylen-bis(4-hydroxy-cumarin), 3,3′-Methylene-bis(4-hydroxycoumarine), 3,3′-Methylenebis(4-hydroxy-1,2-benzopyrone), 3,3′-Methylenebis(4-hydroxy-2H-1-benzopyran-2-one), 3,3′-Methylenebis(4-hydroxycoumarin), bis-3,3′-(4-hydroxycoumarinyl)methane, bis-hydroxycoumarin, Bis(4-hydroxycoumarin-3-yl)methane, di-(4-hydroxy-3-coumarinyl)methane, Dicoumarol, Dicoumarolum, Dicumarol

Status : approved

Category

Anticoagulants

Therapeutic Classification

ANTITHROMBOTIC AGENTS

BLOOD AND BLOOD FORMING ORGANS
ANTITHROMBOTIC AGENTS
ANTITHROMBOTIC AGENTS
Enzyme Inhibitors

Description

An oral anticoagulant that interferes with the metabolism of vitamin K. It is also used in biochemical experiments as an inhibitor of reductases. [PubChem]

Used

For decreasing blood clotting. Often used along with heparin for treatment of deep vein thrombosis.

Mechanism Of Action

Dicumarol inhibits vitamin K reductase, resulting in depletion of the reduced form of vitamin K (vitamin KH2). As vitamin K is a cofactor for the carboxylation of glutamate residues on the N-terminal regions of vitamin K-dependent proteins, this limits the gamma-carboxylation and subsequent activation of the vitamin K-dependent coagulant proteins. The synthesis of vitamin K-dependent coagulation factors II, VII, IX, and X and anticoagulant proteins C and S is inhibited. Depression of three of the four vitamin K-dependent coagulation factors (factors II, VII, and X) results in decresed prothrombin levels and a decrease in the amount of thrombin generated and bound to fibrin. This reduces the thrombogenicity of clots.

Pharmacodynamics

Dicumarol is an coumarin-like compound found in sweet clover. It is used as an oral anticoagulant and acts by inhibiting the hepatic synthesis of vitamin K-dependent coagulation factors (prothrombin and factors VII, IX, and X). It is also used in biochemical experiments as an inhibitor of reductases.

Toxic Effect

LD50=233 mg/kg (orally in mice); LD50=250 mg/kg (orally in rats)

Chemical Classification

This compound belongs to the class of organic compounds known as 4-hydroxycoumarins. These are coumarins that contain one or more hydroxyl groups attached to C4-position the coumarin skeleton.

4-hydroxycoumarins

Organic compounds

Phenylpropanoids and polyketides

Coumarins and derivatives

Hydroxycoumarins

Chemical Name

3,3′-Methylen-bis(4-hydroxy-cumarin)

Drug Drug Interactions

  •  Abciximab  : Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
  •  Acenocoumarol  : May enhance the anticoagulant effect of other Anticoagulants.
  •  Acetylsalicylic acid  : Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
  •  Alteplase  : Thrombolytic Agents may enhance the anticoagulant effect of Anticoagulants.
  •  Aminosalicylic Acid  : Salicylates may enhance the anticoagulant effect of Anticoagulants.
  •  Anagrelide  : Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
  •  Apixaban  : Apixaban may enhance the anticoagulant effect of Anticoagulants.
  •  Argatroban  : May enhance the anticoagulant effect of other Anticoagulants.
  •  Bismuth Subsalicylate  : Salicylates may enhance the anticoagulant effect of Anticoagulants.
  •  Bivalirudin  : May enhance the anticoagulant effect of other Anticoagulants.
  •  Cangrelor  : Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
  •  Celecoxib  : Nonsteroidal Anti-Inflammatory Agents may enhance the anticoagulant effect of Anticoagulants.
  •  Cilostazol  : Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
  •  Citalopram  : Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
  •  Clopidogrel  : Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
  •  Collagenase clostridium histolyticum  : May enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased.
  •  Cyproterone acetate  : Progestins may diminish the therapeutic effect of Anticoagulants. More specifically, the potential prothrombotic effects of some progestins and progestin-estrogen combinations may counteract anticoagulant effects.
  •  Dabigatran etexilate  : Dabigatran etexilate may enhance the anticoagulant effect of Anticoagulants.
  •  Dalteparin  : May enhance the anticoagulant effect of other Anticoagulants.
  •  Danaparoid  : May enhance the anticoagulant effect of other Anticoagulants.
  •  Dasatinib  : Dasatinib may enhance the anticoagulant effect of Anticoagulants.
  •  Deferasirox  : May enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased.
  •  Deoxycholic Acid  : May enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased.
  •  Desogestrel  : Estrogen Derivatives may diminish the anticoagulant effect of Anticoagulants. More specifically, the potential prothrombotic effects of some estrogens and progestin-estrogen combinations may counteract anticoagulant effects.
  •  Desvenlafaxine  : Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
  •  Diclofenac  : Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
  •  Dienogest  : Progestins may diminish the therapeutic effect of Anticoagulants. More specifically, the potential prothrombotic effects of some progestins and progestin-estrogen combinations may counteract anticoagulant effects.
  •  Diflunisal  : Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
  •  Dihydrocodeine  : Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
  •  Dipyridamole  : Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
  •  Drospirenone  : Estrogen Derivatives may diminish the anticoagulant effect of Anticoagulants. More specifically, the potential prothrombotic effects of some estrogens and progestin-estrogen combinations may counteract anticoagulant effects.
  •  Duloxetine  : Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
  •  Edoxaban  : Edoxaban may enhance the anticoagulant effect of Anticoagulants.
  •  Enoxaparin  : May enhance the anticoagulant effect of other Anticoagulants.
  •  Epoprostenol  : Prostacyclin Analogues may enhance the adverse/toxic effect of Anticoagulants. Specifically, the antiplatelet effects of these agents may lead to an increased risk of bleeding with the combination.
  •  Eptifibatide  : Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
  •  Escitalopram  : Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
  •  Estradiol  : Estrogen Derivatives may diminish the anticoagulant effect of Anticoagulants. More specifically, the potential prothrombotic effects of some estrogens and progestin-estrogen combinations may counteract anticoagulant effects.
  •  Estropipate  : Estrogen Derivatives may diminish the anticoagulant effect of Anticoagulants. More specifically, the potential prothrombotic effects of some estrogens and progestin-estrogen combinations may counteract anticoagulant effects.
  •  Ethinyl Estradiol  : Estrogen Derivatives may diminish the anticoagulant effect of Anticoagulants. More specifically, the potential prothrombotic effects of some estrogens and progestin-estrogen combinations may counteract anticoagulant effects.
  •  Ethynodiol  : Estrogen Derivatives may diminish the anticoagulant effect of Anticoagulants. More specifically, the potential prothrombotic effects of some estrogens and progestin-estrogen combinations may counteract anticoagulant effects.
  •  Etodolac  : Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
  •  Etonogestrel  : Progestins may diminish the therapeutic effect of Anticoagulants. More specifically, the potential prothrombotic effects of some progestins and progestin-estrogen combinations may counteract anticoagulant effects.
  •  Fenoprofen  : Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
  •  Floctafenine  : Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
  •  Fluoxetine  : Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
  •  Flurbiprofen  : Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
  •  Fluvoxamine  : Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
  •  Fondaparinux sodium  : May enhance the anticoagulant effect of other Anticoagulants.
  •  Heparin  : May enhance the anticoagulant effect of other Anticoagulants.
  •  Hydroxyprogesterone caproate  : Progestins may diminish the therapeutic effect of Anticoagulants. More specifically, the potential prothrombotic effects of some progestins and progestin-estrogen combinations may counteract anticoagulant effects.
  •  Ibritumomab  : May enhance the adverse/toxic effect of Ibritumomab. Both agents may contribute to an increased risk of bleeding.
  •  Ibrutinib  : Ibrutinib may enhance the adverse/toxic effect of Anticoagulants.
  •  Ibuprofen  : Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
  •  Icosapent  : Omega-3 Fatty Acids may enhance the anticoagulant effect of Anticoagulants.
  •  Icosapent ethyl  : Omega-3 Fatty Acids may enhance the anticoagulant effect of Anticoagulants.
  •  Iloprost  : Prostacyclin Analogues may enhance the adverse/toxic effect of Anticoagulants. Specifically, the antiplatelet effects of these agents may lead to an increased risk of bleeding with the combination.
  •  Indomethacin  : Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
  •  Ketoprofen  : Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
  •  Ketorolac  : Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
  •  Levomilnacipran  : Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
  •  Levonorgestrel  : Progestins may diminish the therapeutic effect of Anticoagulants. More specifically, the potential prothrombotic effects of some progestins and progestin-estrogen combinations may counteract anticoagulant effects.
  •  Magnesium salicylate  : Salicylates may enhance the anticoagulant effect of Anticoagulants.
  •  Medroxyprogesterone Acetate  : Progestins may diminish the therapeutic effect of Anticoagulants. More specifically, the potential prothrombotic effects of some progestins and progestin-estrogen combinations may counteract anticoagulant effects.
  •  Mefenamic acid  : Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
  •  Megestrol acetate  : Progestins may diminish the therapeutic effect of Anticoagulants. More specifically, the potential prothrombotic effects of some progestins and progestin-estrogen combinations may counteract anticoagulant effects.
  •  Meloxicam  : Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
  •  Mestranol  : Estrogen Derivatives may diminish the anticoagulant effect of Anticoagulants. More specifically, the potential prothrombotic effects of some estrogens and progestin-estrogen combinations may counteract anticoagulant effects.
  •  Milnacipran  : Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
  •  Nabumetone  : Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
  •  Nadroparin  : May enhance the anticoagulant effect of other Anticoagulants.
  •  Naproxen  : Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
  •  Nintedanib  : May enhance the adverse/toxic effect of Nintedanib. Specifically, the risk for bleeding may be increased.
  •  Norethindrone  : Progestins may diminish the therapeutic effect of Anticoagulants. More specifically, the potential prothrombotic effects of some progestins and progestin-estrogen combinations may counteract anticoagulant effects.
  •  Norgestimate  : Estrogen Derivatives may diminish the anticoagulant effect of Anticoagulants. More specifically, the potential prothrombotic effects of some estrogens and progestin-estrogen combinations may counteract anticoagulant effects.
  •  Obinutuzumab  : May enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased.
  •  Oxaprozin  : Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
  •  Paroxetine  : Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
  •  Pentosan Polysulfate  : Pentosan Polysulfate Sodium may enhance the anticoagulant effect of Anticoagulants.
  •  Piperazine  : Estrogen Derivatives may diminish the anticoagulant effect of Anticoagulants. More specifically, the potential prothrombotic effects of some estrogens and progestin-estrogen combinations may counteract anticoagulant effects.
  •  Piroxicam  : Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
  •  Prasugrel  : Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
  •  Progesterone  : Progestins may diminish the therapeutic effect of Anticoagulants. More specifically, the potential prothrombotic effects of some progestins and progestin-estrogen combinations may counteract anticoagulant effects.
  •  Reteplase  : Thrombolytic Agents may enhance the anticoagulant effect of Anticoagulants.
  •  Rivaroxaban  : May enhance the anticoagulant effect of Rivaroxaban.
  •  Salsalate  : Salicylates may enhance the anticoagulant effect of Anticoagulants.
  •  Sertraline  : Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
  •  Sulindac  : Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
  •  Tenecteplase  : Thrombolytic Agents may enhance the anticoagulant effect of Anticoagulants.
  •  Tiaprofenic acid  : Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
  •  Ticagrelor  : Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
  •  Ticlopidine  : Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
  •  Tinzaparin  : May enhance the anticoagulant effect of other Anticoagulants.
  •  Tipranavir  : Tipranavir may enhance the anticoagulant effect of Anticoagulants.
  •  Tirofiban  : Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
  •  Tolmetin  : Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
  •  Tositumomab  : May enhance the adverse/toxic effect of Tositumomab and Iodine I 131 Tositumomab. Specifically, the risk of bleeding-related adverse effects may be increased.
  •  Treprostinil  : Prostacyclin Analogues may enhance the adverse/toxic effect of Anticoagulants. Specifically, the antiplatelet effects of these agents may lead to an increased risk of bleeding with the combination.
  •  Venlafaxine  : Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
  •  Vilazodone  : Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
  •  Vitamin E  : Vitamin E may enhance the anticoagulant effect of Anticoagulants. Vitamin E may also increase the overall risk for bleeding.
  •  Vorapaxar  : Vorapaxar may enhance the adverse/toxic effect of Anticoagulants. More specifically, this combination is expected to increase the risk of bleeding.
  •  Vortioxetine  : Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
  •  Warfarin  : May enhance the anticoagulant effect of other Anticoagulants.

Calculated Property

kind Value Source
logP 1.54 ALOGPS
logS -3.7 ALOGPS
Water Solubility 6.62e-02 g/l ALOGPS
logP -1.6 ChemAxon
IUPAC Name 4-hydroxy-3-[(4-hydroxy-2-oxo-2H-chromen-3-yl)methyl]-2H-chromen-2-one ChemAxon
Traditional IUPAC Name dicoumarol ChemAxon
Molecular Weight 336.295 ChemAxon
Monoisotopic Weight 336.063388116 ChemAxon
SMILES OC1=C(CC2=C(O)C3=C(OC2=O)C=CC=C3)C(=O)OC2=C1C=CC=C2 ChemAxon
Molecular Formula C19H12O6 ChemAxon
InChI InChI=1S/C19H12O6/c20-16-10-5-1-3-7-14(10)24-18(22)12(16)9-13-17(21)11-6-2-4-8-15(11)25-19(13)23/h1-8,20-21H,9H2 ChemAxon
InChIKey InChIKey=DOBMPNYZJYQDGZ-UHFFFAOYSA-N ChemAxon
Polar Surface Area (PSA) 93.06 ChemAxon
Refractivity 89.19 ChemAxon
Polarizability 32.32 ChemAxon
Rotatable Bond Count 2 ChemAxon
H Bond Acceptor Count 4 ChemAxon
H Bond Donor Count 2 ChemAxon
pKa (strongest acidic) -12 ChemAxon
pKa (strongest basic) -3.1 ChemAxon
Physiological Charge -1 ChemAxon
Number of Rings 4 ChemAxon
Bioavailability 1 ChemAxon
Rule of Five 1 ChemAxon
Ghose Filter 0 ChemAxon
MDDR-Like Rule 0 ChemAxon

Affected organism

Humans and other mammals

Target within organism

  • Vitamin K epoxide reductase complex subunit 1 : in Human
  • NAD(P)H dehydrogenase [quinone] 1 : in Human
  • Quinone oxidoreductase : in Human