ContaminantDB: Warfarin

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Targets (10)XML

Record Information

Version

1.0

Creation Date

2009-07-05 03:18:12 UTC

Update Date

2026-05-14 16:45:57 UTC

Accession Number

CHEM002093

Identification

Common Name

Warfarin

Class

Small Molecule

Description

Warfarin is an anticoagulant drug normally used to prevent blood clot formation as well as migration. Although originally marketed as a pesticide (d-Con, Rodex, among others), Warfarin has since become the most frequently prescribed oral anticoagulant in North America. Warfarin has several properties that should be noted when used medicinally, including its ability to cross the placental barrier during pregnancy which can result in fetal bleeding, spontaneous abortion, preterm birth, stillbirth, and neonatal death. Additional adverse effects such as necrosis, purple toe syndrome, osteoporosis, valve and artery calcification, and drug interactions have also been documented with warfarin use. Warfarin does not actually affect blood viscosity, rather, it inhibits vitamin-k dependent synthesis of biologically active forms of various clotting factors in addition to several regulatory factors.

Contaminant Sources

Clean Air Act Chemicals
FooDB Chemicals
HMDB Contaminants - Urine
HPV EPA Chemicals
STOFF IDENT Compounds
T3DB toxins
ToxCast & Tox21 Chemicals

Contaminant Type

Anticoagulant
Coumarin and Indandione Rodenticide
Drug
Ester
Food Toxin
Human Neurotoxin
Metabolite
Organic Compound
PMT
Pesticide
Rodenticide
Synthetic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Value	Source
Warfarine	Kegg
Choice	Kegg
(Phenyl-1 acetyl-2 ethyl) 3-hydroxy-4 coumarin	HMDB
(Phenyl-1 acetyl-2 ethyl) 3-hydroxy-4 coumarine	HMDB
(S)-4-Hydroxy-3-(3-oxo-1-phenylbutyl)-2-benzopyrone	HMDB
1-(4'-Hydroxy-3'-coumarinyl)-1-phenyl-3-butanone	HMDB
200 Coumarin	HMDB
3-(1'-Phenyl-2'-acetylethyl)-4-hydroxycoumarin	HMDB
3-(Acetonylbenzyl)-4-hydroxycoumarin	HMDB
3-(alpha-Acetonylbenzyl)-4-hydroxycoumarin	HMDB
3-(alpha-Phenyl-beta-acetylaethyl)-4-hydroxycumarin	HMDB
3-(alpha-Phenyl-beta-acetylethyl)-4-hydroxycoumarin	HMDB
4-Hydroxy-3- (3-oxo-1-fenyl-butyl) cumarine	HMDB
4-Hydroxy-3- (3-oxo-1-phenyl-butyl)-cumarin	HMDB
4-Hydroxy-3-(3-oxo-1-fenyl-butyl) cumarine	HMDB
4-Hydroxy-3-(3-oxo-1-phenyl-butyl)-cumarin	HMDB
4-Hydroxy-3-(3-oxo-1-phenylbutyl)-2H-1-benzopyran-2-one	HMDB, MeSH
4-Hydroxy-3-(3-oxo-1-phenylbutyl)-2H-chromen-2-one	HMDB
4-Hydroxy-3-(3-oxo-1-phenylbutyl)coumarin	HMDB
4-Idrossi-3- (3-oxo-)-fenil-butil)-cumarine	HMDB
4-Idrossi-3-(3-oxo-)-fenil-butil)-cumarine	HMDB
4-Idrossi-3-(3-oxo-1-fenil-butil)-cumarine	HMDB
4oh-Coumarin deriv.	HMDB
Arab rat death	HMDB
Arab rat deth	HMDB
Athrombin-K	HMDB
Athrombine-K	HMDB
Brumolin	HMDB
CO-Rax	HMDB
Compound 42	HMDB
Coumadin	HMDB, MeSH
Coumafen	HMDB
Coumafene	HMDB
Coumaphen	HMDB
Coumaphene	HMDB
Coumarins	HMDB
Coumefene	HMDB
Cov-R-tox	HMDB
D-CON	HMDB
delta-CON	HMDB
Dethmor	HMDB
Dethnel	HMDB
Dicusat e	HMDB
DL-3-(alpha-Acetonylbenzyl)-4-hydroxycoumarin	HMDB
Eastern states duocide	HMDB
fasco Fascrat powder	HMDB
Frass-ratron	HMDB
Killgerm sewarin P	HMDB
Kumader	HMDB
Kumadu	HMDB
Kumatox	HMDB
Kypfarin	HMDB
Latka 42	HMDB
Liqua-tox	HMDB
Maag rattentod cum	HMDB
Mar-frin	HMDB
Martin'S mar-frin	HMDB
Maveran	HMDB
Mouse pak	HMDB
Place-pax	HMDB
Prothromadin	HMDB
Rat & mice bait	HMDB
Rat and mice bait	HMDB
Rat-a-way	HMDB
Rat-alpha-way	HMDB
Rat-b-gon	HMDB
Rat-beta-gon	HMDB
Rat-gard	HMDB
Rat-kill	HMDB
Rat-mix	HMDB
Rat-O-cide #2	HMDB
Rat-O-cide no. 2	HMDB
Rat-ola	HMDB
Rat-trol	HMDB
Ratorex	HMDB
Ratox	HMDB
Ratoxin	HMDB
Ratron	HMDB
Ratron g	HMDB
Rats-NO-more	HMDB
Ratten-koederrohr	HMDB
Rattenstreupulver neu schacht	HMDB
Rattenstreupulver new schacht	HMDB
Rattentraenke	HMDB
Rattunal	HMDB
RAX	HMDB
RCR Grey squirrel killer concentrate	HMDB
ro-Deth	HMDB
Rodafarin	HMDB
Rodafarin c	HMDB
Rodex	HMDB
Rodex blox	HMDB
Rosex	HMDB
Rough & ready mouse mix	HMDB
Rough and ready mouse mix	HMDB
Sakarat	HMDB
Sewarin	HMDB
Solfarin	HMDB
Sorexa plus	HMDB
Spray-trol brand roden-trol	HMDB
Temus W	HMDB
Tox-hid	HMDB
Twin light rat away	HMDB
Vampirinip II	HMDB
Vampirinip III	HMDB
Waran	HMDB
Warfarin sodium	HMDB, MeSH
Zoocoumarin	HMDB
aldo Brand OF warfarin sodium	MeSH, HMDB
apo-Warfarin	MeSH, HMDB
Apotex brand OF warfarin sodium	MeSH, HMDB
Bailly brand OF warfarin sodium	MeSH, HMDB
Boots brand OF warfarin sodium	MeSH, HMDB
Marevan	MeSH, HMDB
Aldocumar	MeSH, HMDB
Coumadine	MeSH, HMDB
Warfant	MeSH, HMDB
Bristol-myers squibb brand OF warfarin sodium	MeSH, HMDB
Genpharm brand OF warfarin sodium	MeSH, HMDB
Goldshield brand OF warfarin sodium	MeSH, HMDB
Sodium, warfarin	MeSH, HMDB
Tedicumar	MeSH, HMDB
Warfarin potassium	MeSH, HMDB
Antigen brand OF warfarin sodium	MeSH, HMDB
Estedi brand OF warfarin sodium	MeSH, HMDB
Gen-warfarin	MeSH, HMDB
Potassium, warfarin	MeSH, HMDB

Chemical Formula

C₁₉H₁₆O₄

Average Molecular Mass

308.328 g/mol

Monoisotopic Mass

308.105 g/mol

CAS Registry Number

81-81-2

IUPAC Name

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

Traditional Name

warfarin

SMILES

CC(=O)CC(C1=CC=CC=C1)C1=C(O)C2=C(OC1=O)C=CC=C2

InChI Identifier

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/h2-10,15,21H,11H2,1H3

InChI Key

PJVWKTKQMONHTI-UHFFFAOYSA-N

Chemical Taxonomy

Description

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.

Kingdom

Organic compounds

Super Class

Phenylpropanoids and polyketides

Class

Coumarins and derivatives

Sub Class

Hydroxycoumarins

Direct Parent

4-hydroxycoumarins

Alternative Parents

Substituents

4-hydroxycoumarin
Benzopyran
1-benzopyran
Pyranone
Monocyclic benzene moiety
Benzenoid
Pyran
Heteroaromatic compound
Vinylogous acid
Ketone
Lactone
Oxacycle
Organoheterocyclic compound
Organic oxygen compound
Carbonyl group
Hydrocarbon derivative
Organic oxide
Organooxygen compound
Aromatic heteropolycyclic compound

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

methyl ketone (CHEBI:87732 )
hydroxycoumarin (CHEBI:87732 )
Coumarin rodenticides (C01541 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Not Available

Biological Roles

Not Available

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

Solid (MSDS, A308).

Experimental Properties

Property	Value
Melting Point	161°C
Boiling Point	Not Available
Solubility	17 mg/L (at 20°C)

Predicted Properties

Property	Value	Source
Water Solubility	0.047 g/L	ALOGPS
logP	2.41	ALOGPS
logP	2.74	ChemAxon
logS	-3.8	ALOGPS
pKa (Strongest Acidic)	5.56	ChemAxon
pKa (Strongest Basic)	-6.9	ChemAxon
Physiological Charge	-1	ChemAxon
Hydrogen Acceptor Count	3	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	63.6 Å²	ChemAxon
Rotatable Bond Count	4	ChemAxon
Refractivity	86.86 m³·mol⁻¹	ChemAxon
Polarizability	31.9 Å³	ChemAxon
Number of Rings	3	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	View
GC-MS	GC-MS Spectrum - EI-B (Non-derivatized)	splash10-014i-0293000000-848341bcbd6a3f0a2c6b	Spectrum
GC-MS	GC-MS Spectrum - EI-B (Non-derivatized)	splash10-014i-0293000000-848341bcbd6a3f0a2c6b	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-0udl-3190000000-b963cb54bb6abedefbe3	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positive	splash10-00xr-7195000000-ca3a892fd51e0eac1242	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_2) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_3) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_3) - 70eV, Positive	Not Available	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , negative	splash10-0a4i-0429000000-1e818b579dc7a0fade2d	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , negative	splash10-03di-0900000000-f568338c06cd9b4762ac	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , negative	splash10-03di-0900000000-acdd0ed19e403aa73c77	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , negative	splash10-0bt9-0539000000-5b1c7c6c812ba72325e3	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , negative	splash10-0a4i-0009000000-e461e1aca7977a2838ad	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-0w29-0960000000-9fa099190280529cd891	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-00di-0910000000-d7dbaf6e7b34ee85e1f7	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-03di-0920000000-4fb886a5c160afa86df9	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-03di-0920000000-ad608fe7680a2adf9d90	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-0ik9-0942000000-5864f2d15892753d6a8b	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 55V, Negative	splash10-03di-0900000000-acdd0ed19e403aa73c77	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 55V, Positive	splash10-0w29-0960000000-b5bc3614bc1379df068c	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 35V, Negative	splash10-0bt9-0539000000-3554db4e3651d4691cbb	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 75V, Positive	splash10-0229-2900000000-022920b191a958c73833	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 60V, Positive	splash10-07vi-5920000000-0506f7adccf44b63822a	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 55V, Negative	splash10-0a4i-0009000000-e461e1aca7977a2838ad	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 80V, Negative	splash10-0a4i-0429000000-1e818b579dc7a0fade2d	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 75V, Positive	splash10-0229-2900000000-6909a3446398afc7d421	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 60V, Positive	splash10-03kc-0910000000-b4521bf9a45fcfff36ac	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0a4l-0197000000-a98e039dbdc8da6c3b7c	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-052f-0292000000-d9a969b41fe312282de6	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-00di-2690000000-f20b105406ab790d37f0	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0a4i-1149000000-4072cf2742b0e6164f82	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0bt9-5988000000-eb075587f79ddb4af966	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-052f-9350000000-47075e4967528dede6f3	Spectrum
MS	Mass Spectrum (Electron Ionization)	splash10-014i-7692000000-6e3993fee62d7eb7438e	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
2D NMR	[1H,13C] 2D NMR Spectrum	Not Available	Spectrum

Toxicity Profile

Route of Exposure

Oral ; Inhalation ; Dermal Rapidly absorbed following oral administration with considerable interindividual variations. Also absorbed percutaneously.

Mechanism of Toxicity

Warfarin 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 decreased prothrombin levels and a decrease in the amount of thrombin generated and bound to fibrin. This reduces the thrombogenicity of clots.

Metabolism

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. In man, the dextrowarfarin enantiomorph is metabolized by side chain reduction to a secondary alcohol, whereas levowarfarin is metabolized by oxidation of the ring, primarily to 7-hydroxywarfarin. These inactive metabolic products are to some extent conjugated with glucuronic acid, undergo an enterohepatic circulation, & are ultimately excreted in urine & stool. (2) Route of 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. Half Life: R-warfarin t_1/2=37-89 hours; S-warfarin t_1/2=21-43 hours.

Toxicity Values

LD50: 374 mg/kg (Oral, Mouse) (1)

Lethal Dose

The lowest reported lethal dose in humans is 6667 ug/kg. (3)

Carcinogenicity (IARC Classification)

No indication of carcinogenicity (not listed by IARC). (12)

Uses/Sources

Warfarin is an anticoagulant drug and rodenticide derived from coumarin. As a drug it is used for the treatment of retinal vascular occlusion, pulmonary embolism, cardiomyopathy, atrial fibrillation and flutter, cerebral embolism, transient cerebral ischaemia, arterial embolism and thrombosis. (1)

Minimum Risk Level

Not Available

Health Effects

Hemorrhage is the most prevalent adverse effect of oral anticoagulant therapy. The incidence of bleeding complications is related to the duration and range of therapy. (13)

Symptoms

LD₅₀=374 (orally in mice)

Treatment

The primary antidote to warfarin poisoning is immediate administration of vitamin K1 (initially slow intravenous injections of 10-25 mg repeated all 3-6 hours until normalisation of the prothrombin time; then 10 mg orally four times daily as a "maintenance dose"). It is an extremely effective antidote, provided the poisoning is caught before too much damage has been done to the victim's circulatory system. At high doses warfarin can affect the body for many months, and the antidote must be administered regularly for a long period of time. (16)

Concentrations

Not Available

External Links

DrugBank ID

Not Available

HMDB ID

Not Available

FooDB ID

Not Available

Phenol Explorer ID

Not Available

KNApSAcK ID

Not Available

BiGG ID

Not Available

BioCyc ID

Not Available

METLIN ID

Not Available

PDB ID

Not Available

Wikipedia Link

Not Available

Chemspider ID

10442445

ChEBI ID

87732

PubChem Compound ID

Not Available

Kegg Compound ID

C01541

YMDB ID

Not Available

ECMDB ID

Not Available

References

Synthesis Reference

Nasri W. Badran, “Microcrystalline 3-(alpha-acetonylbenzyl)-4-hydroxycoumarin (warfarin) and methods of making.” U.S. Patent US4113744, issued April, 1960.

MSDS

Link

General References

Not Available

Warfarin (CHEM002093)

Structure for CHEM002093: Warfarin