COUMARIN

US Previously Marketed

First marketed in 1921

Details

Stereochemistry	ACHIRAL
Molecular Formula	C9H6O2
Molecular Weight	146.1427
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O=C1OC2=C(C=CC=C2)C=C1

InChI

InChIKey=ZYGHJZDHTFUPRJ-UHFFFAOYSA-N

InChI=1S/C9H6O2/c10-9-6-5-7-3-1-2-4-8(7)11-9/h1-6H

HIDE SMILES / InChI

Description
Sources: DOI: 10.4172/2157-7544.1000130
Curator's Comment: description was created based on several sources, including: http://www.inchem.org/documents/jecfa/jecmono/v16je10.htm | https://www.ncbi.nlm.nih.gov/pubmed/20024932

Coumarin itself was first isolated from the tonka bean Coumarouna odorata. Coumarin and its derivatives are alpha-benzopyrones. Coumarin is metabolized in humans to 7-hydroxycoumarin. Coumarin is a secondary phytochemical with hepatotoxic and carcinogenic properties. For the carcinogenic effect, a genotoxic mechanism was considered possible. Coumarins have a significant effect on physiological, bacteriostatic and anti-tumor activity. Coumarins have potent edema protective function and thus involved in the treatment of lymphedema, elephantiasis and other high protein edema conditions. Coumarin has appetite-suppressing properties.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Cytochrome P450 2A6 16 Target ID: CHEMBL5282 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18064444 \| https://www.ncbi.nlm.nih.gov/pubmed/10781881	Inhibitor 8297
Cytochrome P450 2A13 3 Target ID: CHEMBL3542436 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16988941	Inhibitor 8297	6.2 µM [IC50]
Vitamin k epoxide reductase complex subunit 1 isoform 1 22 Target ID: CHEMBL1930 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17635701 \| DOI: 10.1160/TH05-04-0290	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Lymphedema 4 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16000056	Primary	Phase II 1132	Unknown Approved Use Unknown
Post-thrombotic syndrome 2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18639417	Primary	Phase II 1132	Unknown Approved Use Unknown
Acute myocardial infarction 37 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12163424	Preventing	Phase II 1132	Unknown Approved Use Unknown
Allergy 44 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=02d05771-f46d-405d-a7d7-b6e05a7572a7	Primary	Approved 8429	HOMEOPATHIC COUMARIN Approved Use For temporary relief of allergies caused by dairy products, foods, tobacco, wheat, bowel disorders including celiac disease, colitis, poor digestion, back and neck pain and asthma. Launch Date 1.34066877E12

AUC

Value	Dose	Co-administered	Analyte	Population
0.029 mg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/598421	0.857 mg/kg single, oral dose: 0.857 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		COUMARIN blood	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
0.191 mg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/598421	0.25 mg/kg single, intravenous dose: 0.25 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		COUMARIN blood	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
1.018 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/598421	0.857 mg/kg single, oral dose: 0.857 mg/kg route of administration: Oral experiment type: SINGLE co-administered:	COUMARIN blood	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
0.769 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/598421	0.25 mg/kg single, intravenous dose: 0.25 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	COUMARIN blood	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
1.81 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1036930	0.125 mg/kg single, oral dose: 0.125 mg/kg route of administration: Oral experiment type: SINGLE co-administered:	COUMARIN blood	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN
1.45 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1036930	0.2 mg/kg single, oral dose: 0.2 mg/kg route of administration: Oral experiment type: SINGLE co-administered:	COUMARIN blood	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN
1.49 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1036930	0.25 mg/kg single, oral dose: 0.25 mg/kg route of administration: Oral experiment type: SINGLE co-administered:	COUMARIN blood	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
200 mg 2 times / day multiple, oral Studied dose Dose: 200 mg, 2 times / day Route: oral Route: multiple Dose: 200 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9929524 Page: p.349	unhealthy, 33 - 84 n = 139 Health Status: unhealthy Condition: Lymphedema Age Group: 33 - 84 Sex: F Population Size: 139 Sources: https://pubmed.ncbi.nlm.nih.gov/9929524 Page: p.349	Disc. AE: Hepatotoxicity... AEs leading to discontinuation/dose reduction: Hepatotoxicity (6.5%) Sources: https://pubmed.ncbi.nlm.nih.gov/9929524 Page: p.349
7 g 1 times / day multiple, oral (total daily dose) Highest studied dose Dose: 7 g, 1 times / day Route: oral Route: multiple Dose: 7 g, 1 times / day Co-administed with:: cimetidine, p.o(300 mg; 4/day) Sources: https://pubmed.ncbi.nlm.nih.gov/8132703 Page: S 40	unhealthy, 52.8 n = 7 Health Status: unhealthy Condition: Cancer Age Group: 52.8 Sex: M+F Population Size: 7 Sources: https://pubmed.ncbi.nlm.nih.gov/8132703 Page: S 40	DLT: Nausea... Dose limiting toxicities: Nausea (57%) Sources: https://pubmed.ncbi.nlm.nih.gov/8132703 Page: S 40
1600 mg 1 times / day multiple, oral (max) Studied dose Dose: 1600 mg, 1 times / day Route: oral Route: multiple Dose: 1600 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2591993 Page: p.502	unhealthy n = 2173 Health Status: unhealthy Condition: Cancer\|Infections Sex: M+F Population Size: 2173 Sources: https://pubmed.ncbi.nlm.nih.gov/2591993 Page: p.502	DLT: Function liver abnormal... Dose limiting toxicities: Function liver abnormal (0.37%) Sources: https://pubmed.ncbi.nlm.nih.gov/2591993 Page: p.502

AEs

AE	Significance	Dose	Population
Hepatotoxicity	6.5% Disc. AE	200 mg 2 times / day multiple, oral Studied dose Dose: 200 mg, 2 times / day Route: oral Route: multiple Dose: 200 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9929524 Page: p.349	unhealthy, 33 - 84 n = 139 Health Status: unhealthy Condition: Lymphedema Age Group: 33 - 84 Sex: F Population Size: 139 Sources: https://pubmed.ncbi.nlm.nih.gov/9929524 Page: p.349
Nausea	57% DLT, Disc. AE	7 g 1 times / day multiple, oral (total daily dose) Highest studied dose Dose: 7 g, 1 times / day Route: oral Route: multiple Dose: 7 g, 1 times / day Co-administed with:: cimetidine, p.o(300 mg; 4/day) Sources: https://pubmed.ncbi.nlm.nih.gov/8132703 Page: S 40	unhealthy, 52.8 n = 7 Health Status: unhealthy Condition: Cancer Age Group: 52.8 Sex: M+F Population Size: 7 Sources: https://pubmed.ncbi.nlm.nih.gov/8132703 Page: S 40
Function liver abnormal	0.37% DLT, Disc. AE	1600 mg 1 times / day multiple, oral (max) Studied dose Dose: 1600 mg, 1 times / day Route: oral Route: multiple Dose: 1600 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2591993 Page: p.502	unhealthy n = 2173 Health Status: unhealthy Condition: Cancer\|Infections Sex: M+F Population Size: 2173 Sources: https://pubmed.ncbi.nlm.nih.gov/2591993 Page: p.502

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP2A6 543

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2A6 543	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369699/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:28794	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:28794
ChemicalBook	CB3112168	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB3112168
MolPort	MolPort-000-881-054	https://www.molport.com/shop/molecule-link/MolPort-000-881-054
Selleck Chemicals	coumarin	http://www.selleckchem.com/products/coumarin.html
ZINC	ZINC000000074709	http://zinc15.docking.org/substances/ZINC000000074709
eMolecules	494397	https://www.emolecules.com/cgi-bin/more?vid=494397

PubMed

Title	Date	PubMed
Drug interaction: omeprazole and phenprocoumon.	2001	11313000
New lanthanide complexes of 4-methyl-7-hydroxycoumarin and their pharmacological activity.	2001 Apr	11461759
Determination of coumarin metabolism in Turkish population.	2001 Apr	11393269
Interaction of coumarin derivatives with human serum albumin: investigation by fluorescence spectroscopic technique and modeling studies.	2001 Apr	11374572
Prothrombin time ratio is reduced by magnesium contamination in evacuated blood collection tubes.	2001 Apr	11341499
Coumarin formation in novobiocin biosynthesis: beta-hydroxylation of the aminoacyl enzyme tyrosyl-S-NovH by a cytochrome P450 NovI.	2001 Apr	11325587
[Hepatotoxicity of medications].	2001 Apr 14	11360729
Frequency-domain fluorescence microscopy with the LED as a light source.	2001 Aug	11489073
Inhibition and inactivation of human cytochrome P450 isoforms by phenethyl isothiocyanate.	2001 Aug	11454729
Quassinoids from Eurycoma harmandiana.	2001 Aug	11454344
Lack of effect of coumarin on the formation of micronuclei in an in vivo mouse micronucleus assay.	2001 Aug	11434991
Diels--Alder bioconjugation of diene-modified oligonucleotides.	2001 Aug 10	11485455
Chemical constituents of Prangos tschiniganica; structure elucidation and absolute configuration of coumarin and furanocoumarin derivatives with anti-HIV activity.	2001 Jul	11456095
Fenofibrate and warfarin interaction.	2001 Jul	11444587
Screening of organosulfur compounds as inhibitors of human CYP2A6.	2001 Jul	11408364
Neurological outcome in school-age children after in utero exposure to coumarins.	2001 Jul	11408097
A fluorescent receptor assay for benzodiazepines using coumarin-labeled desethylflumazenil as ligand.	2001 Jul 1	11467569
On-wafer spectrofluorometric method for determination of relative quantum yields of photoacid generation in chemically amplified resists.	2001 Jul 15	11476250
Acetoxy-4-methylcoumarins confer differential protection from aflatoxin B(1)-induced micronuclei and apoptosis in lung and bone marrow cells.	2001 Jul 25	11423343
Coumarin derivatives as protease-sensitive prodrugs.	2001 Jun	11475911
[Conservative therapy of acute pelvic-leg vein thrombosis].	2001 Jun	11446064
Cytotoxic constituents of Psoralea corylifolia.	2001 Jun	11440079
Ischaemic jejunal stenosis complicating portal and mesenteric vein thrombosis: a report of two cases.	2001 Jun	11434598
Nicotine metabolism and CYP2A6 allele frequencies in Koreans.	2001 Jun	11434509
Drug interactions as a cause of overanticoagulation on phenprocoumon or acenocoumarol predominantly concern antibacterial drugs.	2001 Jun	11406743
Differing effects of endocrine-disrupting chemicals on basal and FSH-stimulated progesterone production in rat granulosa-luteal cells.	2001 Jun	11395928
Evaluation of methoxsalen, tranylcypromine, and tryptamine as specific and selective CYP2A6 inhibitors in vitro.	2001 Jun	11353760
Consumption of watercress fails to alter coumarin metabolism in humans.	2001 Jun	11353744
[An uncommon cause of severe soft tissue bleeding during phenprocoumon treatment].	2001 Jun 22	11455667
Fine Tuning of physico-chemical parameters to optimise a new series of novobiocin analogues.	2001 Jun 4	11378377
Identification of a single nucleotide polymorphism in the TATA box of the CYP2A6 gene: impairment of its promoter activity.	2001 Jun 8	11394901
Clinical management of protein C deficiency.	2001 Mar	11336597
[Dyspnea caused by spontaneous hematoma of the oropharynx and larynx during marcumar therapy].	2001 Mar	11320626
Effects of scopoletin and aflatoxin B1 on bovine hepatic mitochondrial respiratory complexes, 2: a-ketoglutarate cytochrome c and succinate cytochrome c reductases.	2001 Mar-Apr	11371021
Human cytochrome P450 isozymes in metabolism and health effects of gasoline ethers.	2001 May	11504148
Synthesis, physicochemical characterization, and cytotoxic screening of new zirconium complexes with coumarin derivatives.	2001 May	11413821
Self-management of oral anticoagulation in children with congenital heart disease.	2001 May	11388620
A prenyloxycoumarin from Psiadia dentata.	2001 May	11383617
Mechanism of biochemical action of substituted benzopyran-2-ones. Part 8: Acetoxycoumarin: protein transacetylase specificity for aromatic nuclear acetoxy groups in proximity to the oxygen heteroatom.	2001 May	11377166
Expression of CYP2A6 in tumor cells augments cellular sensitivity to tegafur.	2001 May	11376561
Coumarins isolated from Angelica gigas inhibit acetylcholinesterase: structure-activity relationships.	2001 May	11374978
Prospective study on the usefulness of lung scan in patients with deep vein thrombosis of the lower limbs.	2001 May	11372666
Optimization of an exogenous metabolic activation system for FETAX. I. Post-isolation rat liver microsome mixtures.	2001 May	11360429
Does the location of thrombosis determine the risk of disease recurrence in patients with proximal deep vein thrombosis?	2001 May	11343664
A comparison of aroclor 1254-induced and uninduced rat liver microsomes to human liver microsomes in phenytoin O-deethylation, coumarin 7-hydroxylation, tolbutamide 4-hydroxylation, S-mephenytoin 4'-hydroxylation, chloroxazone 6-hydroxylation and testosterone 6beta-hydroxylation.	2001 May 16	11336973
[Psychiatric comorbidity in somatic disorders. Psychophytopharmaceuticals are worth a try].	2001 May 28	11434262
Antiproliferative effect of isopentenylated coumarins on several cancer cell lines.	2001 May-Jun	11497276
Determination of coumarin in fragrance products by capillary gas chromatography with electron capture detection.	2001 May-Jun	11417632
Role of induction of specific hepatic cytochrome P450 isoforms in epoxidation of 4-vinylcyclohexene.	2001 Sep	11502734
Depentylation of the rat esophageal carcinogen, methyl-n-pentylnitrosamine, by microsomes from various human and rat tissues and by cytochrome P450 2A3.	2001 Sep	11502732

Patents

Sample Use Guides

In Vivo Use Guide

6 mg/kg/day

Route of Administration: Oral

In Vitro Use Guide

Coumarin at concentrations of 100- 500 ug/ml inhibits the incorporation of [3H]thymidine into ACHN cells in a dose-dependent fashion.

Name

Type

Language

COUMARIN

Official Name

English

COUMARIN (PROHIBITED) [FHFI]

Common Name

English

COUMARIN (CONSTITUENT OF CINNAMOMUM CASSIA BARK) [DSC]

Common Name

English

COUMARIN [IARC]

Common Name

English

CIS-O-COUMARINIC ACID LACTONE

Common Name

English

CUMARIN

Common Name

English

Coumarin [WHO-DD]

Common Name

English

COUMARIN [MI]

Common Name

English

COUMARINIC ANHYDRIDE

Systematic Name

English

COUMARINUM

Common Name

English

NCI-C07103

Common Name

English

COUMARIN (CONSTITUENT OF CINNAMOMUM VERUM BARK) [DSC]

Common Name

English

COUMARIN [MART.]

Common Name

English

COUMARIN [INCI]

Common Name

English

COUMARINIC LACTONE

Common Name

English

2-PROPENOIC ACID, 3-(2-HYDROXYPHENYL)-, .DELTA.-LACTONE

Common Name

English

TONKA BEAN CAMPHOR

Common Name

English

2H-1-BENZOPYRAN-2-ONE

Systematic Name

English

2H-BENZO(B)PYRAN-2-ONE

Systematic Name

English

NSC-8774

Code

English

COUMARINUM [HPUS]

Common Name

English

1,2-BENZOPYRONE

Common Name

English

COUMARIN [HSDB]

Common Name

English

O-HYDROXYCINNAMIC ACID LACTONE

Common Name

English

Classification Tree Code System Code

CFR

21 CFR 189.130