2-hydroxy-3-(3-oxo-1-phenylbutyl)-4H-chromen-4-one

• ChemBase ID: 564
• Molecular Formular: C19H16O4
• Molecular Mass: 308.32794
• Monoisotopic Mass: 308.10485899
• SMILES: o1c(O)c(C(CC(=O)C)c2ccccc2)c(=O)c2c1cccc2
• Canonical SMILES: CC(=O)CC(c1c(O)oc2c(c1=O)cccc2)c1ccccc1
• InChI: InChI=1S/C19H16O4/c1-12(20)11-15(13-7-3-2-4-8-13)17-18(21)14-9-5-6-10-16(14)23-19(17)22/h2-10,15,22H,11H2,1H3
• InChIKey: QTXVAVXCBMYBJW-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 2-hydroxy-3-(3-oxo-1-phenylbutyl)-4H-chromen-4-one
• IUPAC Traditional name: rodex
• Brand Name: Warf 42; Warfarat; Warfarin Plus; Warfarin Q; Warfarine; Warficide; Warfilone; Zoocoumarin; Coumadin Tabs; Athrombin; Athrombin-K; Athrombine-K; Brumolin; Co-Rax; Coumadin; Coumafen; Coumafene; Coumaphen; Coumaphene; Coumarins; Coumefene; D-Con; Dethmor; Dethnel; Dicusat E; Frass-Ratron; Jantoven; Kumader; Kumadu; Kumatox; Kypfarin; Latka 42; Mar-Frin; Marevan; Maveran; Panwarfin; Place-Pax; Prothromadin; RAX; Rosex; Sofarin; Solfarin; Sorexa Plus; Temus W; Tintorane; Tox-Hid; Vampirinip II; Vampirinip III
• Synonyms: Warfarin sodium; Warfarin

Database IDs

• CAS Number: 81-81-2
• PubChem SID: 160964027
• PubChem CID: 54678486

CALCULATED PROPERTIES

ALOGPS 2.1

• LOG S: -3.81
• Solubility (Water): 4.77e-02 g/l
• Log P: 2.55

JChem

• Molar Refractivity: 95.9858 cm^3
• Polarizability: 33.25637 Å^3
• Polar Surface Area: 63.6 Å^2
• Rotatable Bonds: 4
• Lipinski's Rule of Five: true
• Acid pKa: 7.5484066
• H Acceptors: 4
• H Donor: 1
• LogD (pH = 5.5): 3.5164902
• LogD (pH = 7.4): 3.2873127
• Log P: 3.5203567

PROPERTIES

Physical Property

• Solubility: 17 mg/L
• Hydrophobicity(logP): 3

DETAILS

DrugBank - DB00682

• Drug Groups: approved
• Description: An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide. [PubChem]
• Indication: For the treatment of retinal vascular occlusion, pulmonary embolism, cardiomyopathy, atrial fibrillation and flutter, cerebral embolism, transient cerebral ischaemia, arterial embolism and thrombosis.
• Pharmacology: Warfarin, a coumarin anticoagulant, is a racemic mixture of two active isomers. It is used in the prevention and treatment of thromboembolic disease including venous thrombosis, thromboembolism, and pulmonary embolism as well as for the prevention of ischemic stroke in patients with atrial fibrillation (AF).
• Toxicity: LD₅₀=374 (orally in mice)
• Affected Organisms: Humans and other mammals
• Biotransformation: Metabolized stereo- and regio-selectively by hepatic microsomal enzymes. S-warfarin is predominantly metabolized by cytochrome P450 (CYP) 2C9 to yield the 6- and 7-hydroxylated metabolites. R-warfarin is metabolized by CYP1A1, 1A2, and 3A4 to yield 6-, 8-, and 10-hydroxylated metabolites. Hydroxylated metabolites may be further conjugated prior to excretion into bile and urine. UGT1A1 appears to be responsible for producing the 6-O-glucuronide of warfarin, with a possibly contribution from UGT1A10. Five UGT1As may be involved in the formation of 7-O-glucuronide warfarin. S-warfarin has higher potency than R-warfarin and genetic polymorphisms in CYP2C9 may dramatically decrease clearance of and increase toxicity of the medication.
• Absorption: Rapidly absorbed following oral administration with considerable interindividual variations. Also absorbed percutaneously.
• Half Life: R-warfarin t_1/2=37-89 hours; S-warfarin t_1/2=21-43 hours.
• Protein Binding: 99% bound primarily to albumin
• Elimination: The elimination of warfarin is almost entirely by metabolism. Very little warfarin is excreted unchanged in urine. The metabolites are principally excreted into the urine; and to a lesser extent into the bile.
• Distribution: * 0.14 L/kg
• Clearance: * 0.065 +/- 0.025 mL/min/kg [CYP2C9 Genotype *1/*1]; * 0.041 +/- 0.021 [CYP2C9 Genotype *1/*2 or *1/*3]; * 0.020 +/- 0.011 [CYP2C9 Genotype *2/*2, *2/*3, or *3/*3]
• References: Ansell J, Hirsh J, Poller L, Bussey H, Jacobson A, Hylek E: The pharmacology and management of the vitamin K antagonists: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004 Sep;126(3 Suppl):204S-233S. [Pubmed] ; Whitlon DS, Sadowski JA, Suttie JW: Mechanism of coumarin action: significance of vitamin K epoxide reductase inhibition. Biochemistry. 1978 Apr 18;17(8):1371-7. [Pubmed] ; Li T, Chang CY, Jin DY, Lin PJ, Khvorova A, Stafford DW: Identification of the gene for vitamin K epoxide reductase. Nature. 2004 Feb 5;427(6974):541-4. [Pubmed] ; Rost S, Fregin A, Ivaskevicius V, Conzelmann E, Hortnagel K, Pelz HJ, Lappegard K, Seifried E, Scharrer I, Tuddenham EG, Muller CR, Strom TM, Oldenburg J: Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. Nature. 2004 Feb 5;427(6974):537-41. [Pubmed] ; Hirsh J, Fuster V, Ansell J, Halperin JL: American Heart Association/American College of Cardiology Foundation guide to warfarin therapy. J Am Coll Cardiol. 2003 May 7;41(9):1633-52. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

REFERENCES

• Ansell J, Hirsh J, Poller L, Bussey H, Jacobson A, Hylek E: The pharmacology and management of the vitamin K antagonists: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004 Sep;126(3 Suppl):204S-233S. Pubmed
• Whitlon DS, Sadowski JA, Suttie JW: Mechanism of coumarin action: significance of vitamin K epoxide reductase inhibition. Biochemistry. 1978 Apr 18;17(8):1371-7. Pubmed
• Li T, Chang CY, Jin DY, Lin PJ, Khvorova A, Stafford DW: Identification of the gene for vitamin K epoxide reductase. Nature. 2004 Feb 5;427(6974):541-4. Pubmed
• Rost S, Fregin A, Ivaskevicius V, Conzelmann E, Hortnagel K, Pelz HJ, Lappegard K, Seifried E, Scharrer I, Tuddenham EG, Muller CR, Strom TM, Oldenburg J: Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. Nature. 2004 Feb 5;427(6974):537-41. Pubmed
• Hirsh J, Fuster V, Ansell J, Halperin JL: American Heart Association/American College of Cardiology Foundation guide to warfarin therapy. J Am Coll Cardiol. 2003 May 7;41(9):1633-52. Pubmed