This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Name
(R)-warfarin
Accession Number
DB08496
Type
Small Molecule
Groups
Experimental
Description

Warfarin consists of a racemic mixture of two active enantiomers—R- and S- forms—each of which is cleared by different pathways. S-warfarin is 2-5 times more potent than the R-isomer in producing an anticoagulant response.[3]

Structure
Thumb
Synonyms
  • (+)-warfarin
  • (R)-4-Hydroxy-3-(3-oxo-1-phenylbutyl)-2-benzopyrone
  • (R)-4-Hydroxy-3-(3-oxo-1-phenylbutyl)-2H-1-benzopyran-2-one
  • 4-hydroxy-3-[(1R)-3-oxo-1-phenylbutyl]-2H-chromen-2-one
  • R,R-Warfarin alcohol
Categories
UNII
09CC5J5C8A
CAS number
40281-89-8
Weight
Average: 308.3279
Monoisotopic: 308.104859
Chemical Formula
C19H16O4
InChI Key
PJVWKTKQMONHTI-OAHLLOKOSA-N
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/h2-10,15,21H,11H2,1H3/t15-/m1/s1
IUPAC Name
4-hydroxy-3-[(1S)-3-oxo-1-phenylbutyl]-2H-chromen-2-one
SMILES
[H][C@@](CC(C)=O)(C1=CC=CC=C1)C1=C(O)C2=CC=CC=C2OC1=O

Pharmacology

Indication
Not Available
Pharmacodynamics
Not Available
Mechanism of action
Not Available
Absorption
Not Available
Volume of distribution

The volume of distribution was 10.9L (95% confidence interval 8.63, 13.2), according to a study by Lane et al. [1]

Protein binding
Not Available
Metabolism

Human liver cytochrome P450 enzymes involved in the 7-hydroxylation of R- and S-warfarin enantiomers.

Route of elimination
Not Available
Half life
Not Available
Clearance

0.125L/h, (95% confidence interval 0.115, 0.135) in a 70kg individual aged 69.8yr with the wild type CYP2C19 and CYP3A4 genotypes.

Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with (R)-warfarin.
AcenocoumarolAcenocoumarol may increase the anticoagulant activities of (R)-warfarin.
AcetaminophenAcetaminophen may increase the anticoagulant activities of (R)-warfarin.
Acetylsalicylic acidAcetylsalicylic acid may increase the anticoagulant activities of (R)-warfarin.
AlclometasoneThe metabolism of (R)-warfarin can be decreased when combined with Alclometasone.
AlteplaseThe risk or severity of bleeding can be increased when Alteplase is combined with (R)-warfarin.
Aminosalicylic AcidAminosalicylic Acid may increase the anticoagulant activities of (R)-warfarin.
AmiodaroneThe therapeutic efficacy of (R)-warfarin can be increased when used in combination with Amiodarone.
AmoxicillinAmoxicillin may increase the anticoagulant activities of (R)-warfarin.
AmpicillinAmpicillin may increase the anticoagulant activities of (R)-warfarin.
Food Interactions
Not Available

References

General References
  1. Lane S, Al-Zubiedi S, Hatch E, Matthews I, Jorgensen AL, Deloukas P, Daly AK, Park BK, Aarons L, Ogungbenro K, Kamali F, Hughes D, Pirmohamed M: The population pharmacokinetics of R- and S-warfarin: effect of genetic and clinical factors. Br J Clin Pharmacol. 2012 Jan;73(1):66-76. doi: 10.1111/j.1365-2125.2011.04051.x. [PubMed:21692828]
  2. Ragueneau-Majlessi I, Levy RH, Meyerhoff C: Lack of effect of repeated administration of levetiracetam on the pharmacodynamic and pharmacokinetic profiles of warfarin. Epilepsy Res. 2001 Nov;47(1-2):55-63. [PubMed:11673021]
  3. 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:12742309]
External Links
PubChem Compound
91546
PubChem Substance
99444967
ChemSpider
10533326
ChEBI
87737
ChEMBL
CHEMBL251073
HET
RWF
PDB Entries
1h9z / 2bxd

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0472 mg/mLALOGPS
logP2.41ALOGPS
logP2.74ChemAxon
logS-3.8ALOGPS
pKa (Strongest Acidic)5.56ChemAxon
pKa (Strongest Basic)-6.9ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area63.6 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity86.86 m3·mol-1ChemAxon
Polarizability32.03 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9109
Blood Brain Barrier+0.9124
Caco-2 permeable+0.8867
P-glycoprotein substrateSubstrate0.5502
P-glycoprotein inhibitor INon-inhibitor0.8782
P-glycoprotein inhibitor IINon-inhibitor0.8382
Renal organic cation transporterNon-inhibitor0.8863
CYP450 2C9 substrateNon-substrate0.678
CYP450 2D6 substrateSubstrate0.5658
CYP450 3A4 substrateNon-substrate0.6007
CYP450 1A2 substrateNon-inhibitor0.714
CYP450 2C9 inhibitorInhibitor0.7657
CYP450 2D6 inhibitorNon-inhibitor0.9286
CYP450 2C19 inhibitorNon-inhibitor0.9161
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8785
Ames testNon AMES toxic0.6844
CarcinogenicityNon-carcinogens0.9352
BiodegradationNot ready biodegradable0.7474
Rat acute toxicity4.1700 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8768
hERG inhibition (predictor II)Non-inhibitor0.9615
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
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.
Kingdom
Organic compounds
Super Class
Phenylpropanoids and polyketides
Class
Coumarins and derivatives
Sub Class
Hydroxycoumarins
Direct Parent
4-hydroxycoumarins
Alternative Parents
1-benzopyrans / Pyranones and derivatives / Benzene and substituted derivatives / Vinylogous acids / Heteroaromatic compounds / Lactones / Ketones / Oxacyclic compounds / Organic oxides / Hydrocarbon derivatives
Substituents
4-hydroxycoumarin / Benzopyran / 1-benzopyran / Pyranone / Monocyclic benzene moiety / Benzenoid / Pyran / Heteroaromatic compound / Vinylogous acid / Ketone
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
4-hydroxy-3-(3-oxo-1-phenylbutyl)-1-benzopyran-2-one (CHEBI:87738)

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Kaminsky LS, Zhang ZY: Human P450 metabolism of warfarin. Pharmacol Ther. 1997;73(1):67-74. [PubMed:9014207]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Curator comments
Very low affinity with little contribution to overall metabolism.
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Kaminsky LS, Zhang ZY: Human P450 metabolism of warfarin. Pharmacol Ther. 1997;73(1):67-74. [PubMed:9014207]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C18
Uniprot ID
P33260
Uniprot Name
Cytochrome P450 2C18
Molecular Weight
55710.075 Da
References
  1. Kaminsky LS, Zhang ZY: Human P450 metabolism of warfarin. Pharmacol Ther. 1997;73(1):67-74. [PubMed:9014207]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Kaminsky LS, Zhang ZY: Human P450 metabolism of warfarin. Pharmacol Ther. 1997;73(1):67-74. [PubMed:9014207]
  2. Kim SY, Kang JY, Hartman JH, Park SH, Jones DR, Yun CH, Boysen G, Miller GP: Metabolism of R- and S-warfarin by CYP2C19 into four hydroxywarfarins. Drug Metab Lett. 2012 Sep 1;6(3):157-64. [PubMed:23331088]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Kaminsky LS, Zhang ZY: Human P450 metabolism of warfarin. Pharmacol Ther. 1997;73(1):67-74. [PubMed:9014207]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d 24-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A1
Uniprot ID
P04798
Uniprot Name
Cytochrome P450 1A1
Molecular Weight
58164.815 Da
References
  1. Kaminsky LS, Zhang ZY: Human P450 metabolism of warfarin. Pharmacol Ther. 1997;73(1):67-74. [PubMed:9014207]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Kaminsky LS, Zhang ZY: Human P450 metabolism of warfarin. Pharmacol Ther. 1997;73(1):67-74. [PubMed:9014207]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]

Drug created on September 15, 2010 15:32 / Updated on September 13, 2018 15:56