| Revision as of 14:53, 15 November 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Script assisted update of identifiers for the Chem/Drugbox validation project (updated: 'DrugBank').← Previous edit |
Latest revision as of 17:18, 18 June 2024 edit undoJJMC89 bot III (talk | contribs)Bots, Administrators3,681,570 editsm Moving Category:Dimerization (chemistry) to Category:Dimers (chemistry) per Misplaced Pages:Categories for discussion/SpeedyTag: Manual revert |
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{{Short description|Chemical compound}} |
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{{distinguish|coumadin|coumarin}} |
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{{distinguish|Coumadin|coumarin}} |
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{{Drugbox |
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{{Drugbox |
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| Verifiedfields = changed |
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| verifiedrevid = 443636646 |
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| Watchedfields = changed |
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| IUPAC_name = 3,3'-methylenebis(4-hydroxy-2''H''-chromen-2-one) |
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| verifiedrevid = 460783797 |
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| IUPAC_name = 3,3'-Methylenebis(4-hydroxy-2''H''-chromen-2-one) |
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| image = Dicumarol.svg |
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| image = Dicumarol.svg |
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| legal_AU = <!-- Unscheduled / S2 / S4 / S8 --> |
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| legal_AU = <!-- Unscheduled / S2 / S4 / S8 --> |
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| legal_UK = <!-- GSL / P / POM / CD --> |
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| legal_UK = <!-- GSL / P / POM / CD --> |
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| legal_US = <!-- OTC / Rx-only --> |
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| legal_US = <!-- Rx-only withdrawn, so no --> |
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| legal_US_comment=Withdrawn from market |
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| legal_status = |
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| legal_status = |
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| routes_of_administration = |
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| routes_of_administration = |
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<!--Pharmacokinetic data--> |
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<!--Pharmacokinetic data--> |
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<!--Identifiers--> |
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<!--Identifiers--> |
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| IUPHAR_ligand = 6808 |
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| CASNo_Ref = {{cascite|correct|CAS}} |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| CAS_number = 66-76-2 |
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| CAS_number = 66-76-2 |
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| ATC_prefix = B01 |
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| ATC_prefix = B01 |
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| ATC_supplemental = |
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| ATC_supplemental = |
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| PubChem = 653 |
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| PubChem = 653 |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| DrugBank_Ref = {{drugbankcite|changed|drugbank}} |
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| DrugBank = <!-- blanked - oldvalue: APRD00761 --> |
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| DrugBank = DB00266 |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID = 10183330 |
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| ChemSpiderID = 10183330 |
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| ChEMBL_Ref = {{ebicite|correct|EBI}} |
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| ChEMBL_Ref = {{ebicite|correct|EBI}} |
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| ChEMBL = 1466 |
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| ChEMBL = 1466 |
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| NIAID_ChemDB = 016070 |
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<!--Chemical data--> |
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<!--Chemical data--> |
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| C=19 | H=12 | O=6 |
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| C=19 | H=12 | O=6 |
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| SMILES = O=C1Oc2ccccc2C(O)=C1CC3=C(O)c4ccccc4OC3=O |
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| molecular_weight = 336.295 g/mol |
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| smiles = c1ccc2c(c1)c(c(c(=O)o2)Cc3c(c4ccccc4oc3=O)O)O |
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| InChI = 1/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 |
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| InChIKey = DOBMPNYZJYQDGZ-UHFFFAOYAT |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI = 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 |
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| StdInChI = 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 |
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'''Dicoumarol''' (]) or '''dicumarol''' (]) is an ] that functions as a ] antagonist (similar to ], for which it was the inspiration). It is also used in biochemical experiments as an inhibitor of reductases. |
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'''Dicoumarol''' (]) or '''dicumarol''' (]) is a naturally occurring ] drug that depletes stores of ] (similar to ], a drug that dicoumarol inspired). It is also used in biochemical experiments as an inhibitor of ]. |
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Dicoumarol is a natural chemical substance of combined plant and fungal origin. It is a derivative of ], a bitter substance made by plants that does not itself affect coagulation, but which is (classically) transformed in mouldy feeds or silages by a number of species of fungi, into active dicoumarol. Dicoumarol ''does'' affect coagulation, and was discovered in mouldy wet sweet-clover hay, as the cause of a naturally occurring bleeding disease in cattle. |
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Dicoumarol is a natural chemical substance of combined plant and fungal origin. It is a derivative of ], a bitter-tasting but sweet-smelling substance made by plants that does not itself affect coagulation, but which is (classically) transformed in mouldy feeds or silages by a number of species of fungi, into active dicoumarol. Dicoumarol does affect coagulation, and was discovered in mouldy wet sweet-clover hay, as the cause of a naturally occurring bleeding disease in cattle.<ref>{{cite journal | vauthors = Kresge N, Simoni RD, Hill RL | title = Hemorrhagic sweet clover disease, dicumarol, and warfarin: the work of Karl Paul Link. | journal = Journal of Biological Chemistry | date = February 2005 | volume = 280 | issue = 8 | pages = e6-e7 | doi = 10.1016/S0021-9258(19)62862-0 | doi-access = free }}</ref> See ] for a more detailed discovery history. |
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Identified in 1940, dicoumarol became the prototype of the ] derivative anticoagulant drug class. Dicoumarol itself, for a short time, was employed as a medicinal anticoagulant drug, but since the mid-1950s has been replaced by its simpler derivative ], and other 4-hydroxycoumarin drugs. |
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Identified in 1940, dicoumarol became the prototype of the ]. Dicoumarol itself, for a short time, was employed as a medicinal anticoagulant drug, but since the mid-1950s has been replaced by its simpler derivative ], and other 4-hydroxycoumarin drugs. |
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It is given only orally, and it acts within two days. |
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It is given orally, and it acts within two days. |
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==Mechanism of action== |
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== Uses == |
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Dicoumarol was used, along with ], for the treatment of deep venous thrombosis. Unlike heparin, this class of drugs may be used for months or years. |
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Like all ] drugs it is a competitive inhibitor of ], preventing the formation of prothrombin. Administration of vitamin K is therefore the antidote for dicoumarol toxicity. The toxicity and the antidote effectiveness are measuring with the ] (PT) blood test. |
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== Mechanism of action == |
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==Uses== |
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Like all 4-hydroxycoumarin drugs it is a ] of ], an enzyme that recycles ], thus causing depletion of active vitamin K in blood. This prevents the formation of the active form of ] and several other coagulant enzymes. These compounds are not antagonists of Vitamin K directly—as they are in pharmaceutical uses—but rather promote depletion of vitamin K in bodily tissues allowing vitamin K's mechanism of action as a potent medication for dicoumarol toxicity. The mechanism of action of Vitamin K along with the toxicity of dicoumarol are measured with the ] (PT) blood test. |
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Dicoumarol was used along with heparin, for the treatment of deep venous thrombosis. Unlike heparin, this class of drugs may be used for months or years. |
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==References== |
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== Poisoning == |
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] results in serious, sometimes fatal uncontrolled ].<ref>{{cite journal | vauthors = Duff IF, Shull WH | title = Fatal hemorrhage in dicumarol poisoning; with report of necropsy | journal = Journal of the American Medical Association | volume = 139 | issue = 12 | pages = 762–766 | date = March 1949 | pmid = 18112552 | doi = 10.1001/jama.1949.02900290008003 }}</ref> |
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{{nofootnotes|date=September 2011}} |
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* {{cite journal | author = Cullen J, Hinkhouse M, Grady M, Gaut A, Liu J, Zhang Y, Weydert C, Domann F, Oberley L | title = Dicumarol inhibition of NADPH: quinone oxidoreductase induces growth inhibition of pancreatic cancer via a superoxide-mediated mechanism. | journal = Cancer Res | volume = 63 | issue = 17 | pages = 5513–20 | year = 2003 | pmid = 14500388}} |
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* {{cite journal | author = Mironov A, Colanzi A, Polishchuk R, Beznoussenko G, Mironov A, Fusella A, Di Tullio G, Silletta M, Corda D, De Matteis M, Luini A | title = Dicumarol, an inhibitor of ADP-ribosylation of CtBP3/BARS, fragments golgi non-compact tubular zones and inhibits intra-golgi transport. | journal = Eur J Cell Biol | volume = 83 | issue = 6 | pages = 263–79 | year = 2004 | pmid = 15511084 | doi = 10.1078/0171-9335-00377}} |
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* {{cite journal | author = Abdelmohsen K, Stuhlmann D, Daubrawa F, Klotz L | title = Dicumarol is a potent reversible inhibitor of gap junctional intercellular communication. | journal = Arch Biochem Biophys | volume = 434 | issue = 2 | pages = 241–7 | year = 2005 | pmid = 15639223 | doi = 10.1016/j.abb.2004.11.002}} |
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* {{cite journal | author = Thanos C, Liu Z, Reineke J, Edwards E, Mathiowitz E | title = Improving relative bioavailability of dicumarol by reducing particle size and adding the adhesive poly(fumaric-co-sebacic) anhydride. | journal = Pharm Res | volume = 20 | issue = 7 | pages = 1093–100 | year = 2003 | pmid = 12880296 | doi = 10.1023/A:1024474609667}}] |
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==External links== |
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==History== |
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Dicoumarol was isolated by ]'s laboratory at University of Wisconsin, six years after a farmer had brought a dead cow and a milk can full of uncoagulated blood to an ] station of the university. The cow had died of internal bleeding after eating moldy sweet clover; an outbreak of such deaths had begun in the 1920s during ] as farmers could not afford to waste hay that had gone bad.<ref name=Wardrop>{{cite journal | vauthors = Wardrop D, Keeling D | title = The story of the discovery of heparin and warfarin | journal = British Journal of Haematology | volume = 141 | issue = 6 | pages = 757–763 | date = June 2008 | pmid = 18355382 | doi = 10.1111/j.1365-2141.2008.07119.x | doi-access = free }}</ref> Link's work led to the development of the rat poison ] and then to the anticoagulants still in clinical use today.<ref name=Wardrop/> |
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== See also == |
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*] |
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== References == |
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{{reflist}} |
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== Further reading == |
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{{more footnotes|date=September 2011}} |
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{{refbegin}} |
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* {{cite journal | vauthors = Cullen JJ, Hinkhouse MM, Grady M, Gaut AW, Liu J, Zhang YP, Weydert CJ, Domann FE, Oberley LW | display-authors = 6 | title = Dicumarol inhibition of NADPH:quinone oxidoreductase induces growth inhibition of pancreatic cancer via a superoxide-mediated mechanism | journal = Cancer Research | volume = 63 | issue = 17 | pages = 5513–5520 | date = September 2003 | pmid = 14500388 }} |
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* {{cite journal | vauthors = Mironov AA, Colanzi A, Polishchuk RS, Beznoussenko GV, Mironov AA, Fusella A, Di Tullio G, Silletta MG, Corda D, De Matteis MA, Luini A | display-authors = 6 | title = Dicumarol, an inhibitor of ADP-ribosylation of CtBP3/BARS, fragments golgi non-compact tubular zones and inhibits intra-golgi transport | journal = European Journal of Cell Biology | volume = 83 | issue = 6 | pages = 263–279 | date = July 2004 | pmid = 15511084 | doi = 10.1078/0171-9335-00377 }} |
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* {{cite journal | vauthors = Abdelmohsen K, Stuhlmann D, Daubrawa F, Klotz LO | title = Dicumarol is a potent reversible inhibitor of gap junctional intercellular communication | journal = Archives of Biochemistry and Biophysics | volume = 434 | issue = 2 | pages = 241–247 | date = February 2005 | pmid = 15639223 | doi = 10.1016/j.abb.2004.11.002 }} |
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* {{cite journal | vauthors = Thanos CG, Liu Z, Reineke J, Edwards E, Mathiowitz E | title = Improving relative bioavailability of dicumarol by reducing particle size and adding the adhesive poly(fumaric-co-sebacic) anhydride | journal = Pharmaceutical Research | volume = 20 | issue = 7 | pages = 1093–1100 | date = July 2003 | pmid = 12880296 | doi = 10.1023/A:1024474609667 | s2cid = 448086 }}] |
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{{refend}} |
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== External links == |
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* {{DiseasesDB|30166}} |
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* {{DiseasesDB|30166}} |
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