ACENOCOUMAROL

US Previously Marketed

First approved in 1957

Details

Stereochemistry	RACEMIC
Molecular Formula	C19H15NO6
Molecular Weight	353.3262
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(=O)CC(c1ccc(cc1)N(=O)=O)c2c(c3ccccc3oc2=O)O

InChI

InChIKey=VABCILAOYCMVPS-UHFFFAOYSA-N

InChI=1S/C19H15NO6/c1-11(21)10-15(12-6-8-13(9-7-12)20(24)25)17-18(22)14-4-2-3-5-16(14)26-19(17)23/h2-9,15,22H,10H2,1H3

HIDE SMILES / InChI

Description
Sources: https://www.esciencecentral.org/journals/acenocoumarol-in-thromoembolic-disorders-2329-6607-1000157.php?aid=61383
Curator's Comment:: Description was created based on several sources, including https://www.old.health.gov.il/units/pharmacy/trufot/alonim/4140.pdf | https://www.ncbi.nlm.nih.gov/pubmed/27730796

Acenocoumarol is mono-coumarin derivative with racemic mixture of R (+) and S (-) enantiomers. Acenocoumarol is structurally similar to vitamin K and is competitively able to inhibit the enzyme vitamin K-epoxide reductase. It exerts anticoagulant action by preventing the regeneration of reduced vitamin K by interfering with action of vitamin K epoxide reductase. Acenocoumarol is prescribed as the anticoagulant in various thromboembolic disorders.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Vitamin k epoxide reductase complex subunit 1 isoform 1 21 Target ID: CHEMBL1930 Sources: https://www.esciencecentral.org/journals/acenocoumarol-in-thromoembolic-disorders-2329-6607-1000157.php?aid=61383	Inhibitor 7687

Conditions

Condition	Modality	Highest Phase	Product
Venous thromboembolism 11 Sources: https://www.esciencecentral.org/journals/acenocoumarol-in-thromoembolic-disorders-2329-6607-1000157.php?aid=61383 https://www.ncbi.nlm.nih.gov/pubmed/27730796	Primary	Approved 7968	SINTROM Approved Use Prophylaxis and treatment of venous thromboembolism, Atrial fibrillation, Post-myocardial infarction (with increased risk for thromboembolic complications), Bioprosthetic heart valves, Mechanical heart valves
Atrial fibrillation 130 Sources: https://www.esciencecentral.org/journals/acenocoumarol-in-thromoembolic-disorders-2329-6607-1000157.php?aid=61383 https://www.ncbi.nlm.nih.gov/pubmed/27730796	Primary	Approved 7968	SINTROM Approved Use Prophylaxis and treatment of venous thromboembolism, Atrial fibrillation, Post-myocardial infarction (with increased risk for thromboembolic complications), Bioprosthetic heart valves, Mechanical heart valves
Post-myocardial infarction (with increased risk for thromboembolic complications) 2 Sources: https://www.esciencecentral.org/journals/acenocoumarol-in-thromoembolic-disorders-2329-6607-1000157.php?aid=61383 https://www.ncbi.nlm.nih.gov/pubmed/27730796	Primary	Approved 7968	SINTROM Approved Use Prophylaxis and treatment of venous thromboembolism, Atrial fibrillation, Post-myocardial infarction (with increased risk for thromboembolic complications), Bioprosthetic heart valves, Mechanical heart valves

C_max

Value	Dose	Co-administered	Analyte	Population
60 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12844136/	8 mg single, oral dose: 8 mg route of administration: Oral experiment type: SINGLE co-administered:		ACENOCOUMAROL, (S)- plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
360 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12844136/	8 mg single, oral dose: 8 mg route of administration: Oral experiment type: SINGLE co-administered:		ACENOCOUMAROL, (R)- plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
205.9 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12844136/	8 mg single, oral dose: 8 mg route of administration: Oral experiment type: SINGLE co-administered:		ACENOCOUMAROL, (S)- plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
2602 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12844136/	8 mg single, oral dose: 8 mg route of administration: Oral experiment type: SINGLE co-administered:		ACENOCOUMAROL, (R)- plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12844136/	8 mg single, oral dose: 8 mg route of administration: Oral experiment type: SINGLE co-administered:		ACENOCOUMAROL, (S)- plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
8.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12844136/	8 mg single, oral dose: 8 mg route of administration: Oral experiment type: SINGLE co-administered:		ACENOCOUMAROL, (R)- plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
	substrate 865

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
MRP2 341	P-gp 1222 MRP1 75 MRP2 172 BCRP 461 CYP1A2 892 CYP2C19 830

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
MRP2 421	inhibitor 2612 Sources: https://pubmed.ncbi.nlm.nih.gov/27925230/	yes

Drug as victim

Target	Modality	Activity
CYP2C9 865	substrate 2751 Sources: https://pubmed.ncbi.nlm.nih.gov/11038154/	major
CYP1A2 892	substrate 2751 Sources: https://pubmed.ncbi.nlm.nih.gov/11038154/	minor
CYP2C19 830	substrate 2751 Sources: https://pubmed.ncbi.nlm.nih.gov/11038154/	minor
P-gp 1222	substrate 2751 Sources: https://pubmed.ncbi.nlm.nih.gov/27925230/ \| https://pubmed.ncbi.nlm.nih.gov/23663291/	weak
BCRP 461	substrate 2751 Sources: https://pubmed.ncbi.nlm.nih.gov/27925230/	yes
MRP1 75	substrate 2751 Sources: https://pubmed.ncbi.nlm.nih.gov/27925230/	yes
MRP2 172	substrate 2751 Sources: https://pubmed.ncbi.nlm.nih.gov/27925230/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:53766	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:53766
ChemicalBook	CB9114003	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB9114003
MolPort	MolPort-002-798-798	https://www.molport.com/shop/molecule-link/MolPort-002-798-798
eMolecules	902195	https://www.emolecules.com/cgi-bin/more?vid=902195

PubMed

Title	Date	PubMed
[Acute renal insufficiency caused by bilateral arterial thrombosis in a patient undergoing heparin treatment].	2002	12369135
Factors predictive of failure of Brescia-Cimino arteriovenous fistulas.	2002	12022368
[Half-stay and morbidity in a cohort of patients treated with urologic surgery iin the treatment with acenocumarol (Sintrom)].	2002 Apr	12090184
Thumbprinting due to ischemic colitis in a patient on oral anticoagulation.	2002 Aug-Sep	12403394
[Warfarin fetopathy].	2002 Jul	12162160
Low dose oral vitamin K to reverse acenocoumarol-induced coagulopathy: a randomized controlled trial.	2002 Jul	12152676
Role of oral anticoagulation and inoue balloon mitral valvulotomy in presence of left atrial thrombus: a prospective serial transesophageal echocardiographic study.	2002 Jul	12150310
Leu208Val and Ile181Leu variants of cytochrome P450 CYP2C9 are not related to the acenocoumarol dose requirement in a Spanish population.	2002 Jul 15	12123234
Effect of low-dose aspirin on the international normalized ratio variability in patients with mechanical heart valve prostheses.	2002 Jul-Aug	12759515
[Oral anticoagulant treatment: practical aspects and significance of anticoagulant clinics].	2002 Jun	12471648
Initiation of oral anticoagulant therapy in orthopedic and surgical patients: an algorithm compared with routine dosing.	2002 Jun	12162272
Overanticoagulation associated with combined use of antifungal agents and coumarin anticoagulants.	2002 Jun	12087353
Therapeutic quality control of oral anticoagulant therapy comparing the short-acting acenocoumarol and the long-acting phenprocoumon.	2002 Jun	12060134
Re: Webster K, Wilde J. Management of anticoagulation in patients with prosthetic heart valves undergoing oral and maxillofacial operations. Br J Oral Maxillofac Surg 2000; 38: 124-126.	2002 Jun	12054729
[HELLP syndrome associated to pulmonary thromboembolism and factor V Leiden].	2002 Jun 1	12049698
Platelet aggregation in different antithrombotic regimens. Possible proaggregant effect of low level oral anticoagulation.	2002 May	12174518
Treatment with vitamin K antagonists: frequency of indications and appropriateness of continuation.	2002 May-Jun	12372923
[Acenocoumarol (Sintrom) and fluinidione (Previscan) in pediatrics after cardiac surgical procedures].	2002 Nov	12503504
Overanticoagulation associated with combined use of antibacterial drugs and acenocoumarol or phenprocoumon anticoagulants.	2002 Nov	12428081
Pharmacogenetics of acenocoumarol: cytochrome P450 CYP2C9 polymorphisms influence dose requirements and stability of anticoagulation.	2002 Nov	12414349
The potential interaction between oral anticoagulants and acetaminophen in everyday practice.	2002 Oct	12426965
Relationship between international normalized ratio values, vitamin K-dependent clotting factor levels and in vivo prothrombin activation during the early and steady phases of oral anticoagulant treatment.	2002 Oct	12368163
Extended venous thromboembolism prophylaxis after total hip replacement: a comparison of low-molecular-weight heparin with oral anticoagulant.	2002 Oct 28	12390061
No effect of acenocoumarol therapy on levels of endothelial activation markers in sickle cell disease.	2002 Sep	12221677
Intracranial bleeding: epidemiology and relationships with antithrombotic treatment in 241 cerebral hemorrhages in Reggio Emilia.	2002 Sep	12217807
The first experience with endovascular stenting of the iliac veins in patients suffering from post-thrombophlebitic disease.	2003	12811390
Acenocoumarol is not a safe alternative for anticoagulation in phenprocoumon-induced hepatic failure. Report of two cases.	2003	12743448
Ischaemic stroke in young people: a prospective and long-term follow-up study.	2003	12499721
[Prevention of postoperative bleeding in patients taking oral anticoagulants. Effects of tranexamic acid].	2003 Apr	12750624
Low rate of bleeding and thrombotic complications of oral anticoagulant therapy independent of age in the real-practice of an anticoagulation clinic.	2003 Apr	12695750
Acenocoumarol therapy in pediatric patients.	2003 Aug	12911587
Comparison of control and stability of oral anticoagulant therapy using acenocoumarol versus phenprocoumon.	2003 Aug	12888873
[Oral anticoagulation with vitamin K antagonists].	2003 Jan	12638470
Major bleeding during combined treatment with indomethacin and low doses of acenocoumarol in a homozygous patient for 2C9*3 variant of cytochrome p-450 CYP2C9.	2003 Jul	12876643
Oral anticoagulant therapy: should doctors change the way they give patients explanations?	2003 Jul	12876642
Impact of pre-treatment INR level on the effect of intravenous low dose vitamin K in patients with excessive anticoagulation.	2003 Jul	12876628
Capillary whole blood testing by a new portable monitor. Comparison with standard determination of the international normalized ratio.	2003 Jul	12866369
Acenocoumarol pharmacokinetics in relation to cytochrome P450 2C9 genotype.	2003 Jul	12844136
Cluster-like headache due to warfarin therapy?	2003 Jul	12807529
Summaries for patients. How long should blood thinners be given to patients who have had a pulmonary embolism?	2003 Jul 1	12834333
Extended oral anticoagulant therapy after a first episode of pulmonary embolism.	2003 Jul 1	12834314
Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer.	2003 Jul 10	12853587
Pharmacokinetic study of the digoxin-acenocoumarol interaction in rabbits.	2003 Jun	12808292
[Excess antivitamin K in elderly hospitalised patients aged over 70. A one-year prospective survey].	2003 Jun 14	12876525
A placebo-controlled pharmacodynamic and pharmacokinetic interaction study between tamsulosin and acenocoumarol.	2003 Mar	12630984
[Pharmacological interactions of statins].	2003 Mar 15	12681161
Clozapine and venous thromboembolism: further evidence.	2003 May	12755667
Pharmacogenetics of oral anticoagulants.	2003 May	12724615
Experience with enoxaparin in patients with mechanical heart valves who must withhold acenocumarol.	2003 May	12695457
Rofecoxib interaction with oral anticoagulant acenocoumarol.	2003 Sep	12898082

Patents

Sample Use Guides

In Vivo Use Guide

The dosing of Sintrom (acenocoumarol) must be individualized. The usual starting dose of Sintrom in a normal weight person is between 2 mg/day to 4 mg/day without administration of a loading dose, if the prothrombine time (PT)/ International Normalized Ratio (INR) value before the start of treatment is within the normal range. Treatment may also be initiated with a loading dose regimen, usually 6 mg on the first day followed by 4 mg on the second day.

Route of Administration: Oral

In Vitro Use Guide

Acenocoumarol had no effect in unstimulated cells but in PHA-stimulated PBMC tryptophan breakdown and the formation of neopterin, as well as IFN-γ and TNF-α, were dose-dependently suppressed at concentrations as low as 10 μg/ml. Likewise, acenocoumarol dose-dependently inhibited tryptophan breakdown in IFN-γ stimulated Caco-2 cells. Interestingly, NF-κB expression was super-induced in the LPS treated cells.

Name

Type

Language

ACENOCOUMAROL

Official Name

English

MINI-SINTROM

Brand Name

English

NSC-760052

Code

English

2H-1-BENZOPYRAN-2-ONE, 4-HYDROXY-3-(1-(4-NITROPHENYL)-3-OXOBUTYL)-

Systematic Name

English

3-(.ALPHA.-ACETONYL-P-NITROBENZYL)-4-HYDROXYCOUMARIN

Common Name

English

ACENOCOUMAROL [WHO-DD]

Common Name

English

ACENOCOUMAROL [HSDB]

Common Name

English

ACENOCOUMAROL [MART.]

Common Name

English

ACENOCOUMAROL [INN]

Common Name

English

ACENOCOUMARIN

Common Name

English

ACENOCOUMAROL [MI]

Common Name

English

NICOUMALONE

Common Name

English

Classification Tree Code System Code

WHO-ATC

B01AA07