Acenocoumarol (CED0004979)

Record Information

Version

1.0

Creation Date

2009-07-23 18:26:19 UTC

Update Date

2026-05-14 17:00:16 UTC

Accession Number

CHEM002440

Identification

Common Name

Acenocoumarol

Class

Small Molecule

Description

Acenocoumarol is an exogenous solid with the formula C19H15NO6 and an average molecular weight of 353.33 g/mol. Acenocoumarol belongs to the hydroxycoumarins, a subclass of coumarins and derivatives within the organic compounds. It is used as an anticoagulant and acts as an inhibitor of EC 1.6.5.2 [NAD(P)H dehydrogenase (quinone)]. This compound is found in amplifiers and in antithrombotic agents within healthcare, pharmaceuticals, and veterinary products, with oral exposure recorded. The protein targets of acenocoumarol include albumin (ALB), alpha-1-acid glycoprotein 1 (ORM1), and vitamin K epoxide reductase complex subunit 1 (VKORC1). Acenocoumarol inhibits vitamin K reductase, which leads to the depletion of the reduced form of vitamin K (vitamin KH2). Because vitamin K serves as a cofactor for the carboxylation of glutamate residues on the N-terminal regions of vitamin K-dependent proteins, this inhibition limits gamma-carboxylation and the subsequent activation of vitamin K-dependent coagulant proteins. Consequently, the synthesis of anticoagulant proteins C and S, as well as vitamin K-dependent coagulation factors II, VII, IX, and X, is inhibited.

Contaminant Type

Anticoagulant
Aromatic Hydrocarbon
Drug
Ester
Human Neurotoxin
Metabolite
Organic Compound
Synthetic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Value	Source
3-(alpha-(4'-Nitrophenyl)-beta-acetylethyl)-4-hydroxycoumarin	ChEBI
3-(alpha-(p-Nitrophenol)-beta-acetylethyl)-4-hydroxycoumarin	ChEBI
3-(alpha-Acetonyl-4-nitrobenzyl)-4-hydroxycoumarin	ChEBI
3-(alpha-Acetonyl-p-nitrobenzyl)-4-hydroxycoumarin	ChEBI
3-(alpha-p-Nitrophenyl-beta-acetylethyl)-4-hydroxycoumarin	ChEBI
4-Hydroxy-3-(1-(4-nitrophenyl)-3-oxobutyl)-2H-1-benzopyran-2-one	ChEBI
4-Hydroxy-3-[1-(4-nitrophenyl)-3-oxobutyl]-2H-chromen-2-one	ChEBI
Acenocoumarin	ChEBI
Acenocoumarolum	ChEBI
Acenocumarol	ChEBI
Acenocumarolo	ChEBI
Acenokumarin	ChEBI
Nicoumalone	ChEBI
Nicumalon	ChEBI
Nitrophenylacetylethyl-4-hydroxycoumarine	ChEBI
Nitrovarfarian	ChEBI
Nitrowarfarin	ChEBI
Mini-sintrom	Kegg
3-(a-(4'-Nitrophenyl)-b-acetylethyl)-4-hydroxycoumarin	Generator
3-(Α-(4'-nitrophenyl)-β-acetylethyl)-4-hydroxycoumarin	Generator
3-(a-(p-Nitrophenol)-b-acetylethyl)-4-hydroxycoumarin	Generator
3-(Α-(p-nitrophenol)-β-acetylethyl)-4-hydroxycoumarin	Generator
3-(a-Acetonyl-4-nitrobenzyl)-4-hydroxycoumarin	Generator
3-(Α-acetonyl-4-nitrobenzyl)-4-hydroxycoumarin	Generator
3-(a-Acetonyl-p-nitrobenzyl)-4-hydroxycoumarin	Generator
3-(Α-acetonyl-p-nitrobenzyl)-4-hydroxycoumarin	Generator
3-(a-p-Nitrophenyl-b-acetylethyl)-4-hydroxycoumarin	Generator
3-(Α-p-nitrophenyl-β-acetylethyl)-4-hydroxycoumarin	Generator
Ciba-geigy brand OF acenocoumarol	HMDB
Mini sintrom	HMDB
Novartis brand OF acenocoumarol	HMDB
Sinkumar	HMDB
Syncoumar	HMDB
Synthrom	HMDB
Acenocoumarol alliance brand	HMDB
Acenocoumarol novartis brand	HMDB
Alliance brand OF acenocoumarol	HMDB
Ciba geigy brand OF acenocoumarol	HMDB
MiniSintrom	HMDB
Syncumar	HMDB
Acenocoumarol ciba-geigy brand	HMDB
Sinthrome	HMDB
Sintrom	HMDB

Chemical Formula

C₁₉H₁₅NO₆

Average Molecular Mass

353.326 g/mol

Monoisotopic Mass

353.090 g/mol

CAS Registry Number

152-72-7

IUPAC Name

4-hydroxy-3-[1-(4-nitrophenyl)-3-oxobutyl]-2H-chromen-2-one

Traditional Name

acenocumarolo

SMILES

CC(=O)CC(C1=CC=C(C=C1)[N+]([O-])=O)C1=C(O)C2=CC=CC=C2OC1=O

InChI Identifier

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

InChI Key

VABCILAOYCMVPS-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
Nitrobenzene
Nitroaromatic compound
Pyranone
Monocyclic benzene moiety
Pyran
Benzenoid
Heteroaromatic compound
Vinylogous acid
Ketone
Lactone
C-nitro compound
Organic nitro compound
Oxacycle
Organic oxoazanium
Organoheterocyclic compound
Allyl-type 1,3-dipolar organic compound
Propargyl-type 1,3-dipolar organic compound
Organic 1,3-dipolar compound
Organopnictogen compound
Hydrocarbon derivative
Organooxygen compound
Organonitrogen compound
Organic oxide
Organic oxygen compound
Organic nitrogen compound
Carbonyl group
Aromatic heteropolycyclic compound

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

C-nitro compound (CHEBI:53766 )
methyl ketone (CHEBI:53766 )
hydroxycoumarin (CHEBI:53766 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Extracellular
Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Applications

anticoagulant

Biological Roles

EC 1.6.5.2 [NAD(P)H dehydrogenase (quinone)] inhibitor

Chemical Roles

EC 1.6.5.2 [NAD(P)H dehydrogenase (quinone)] inhibitor

Organoleptic Effects

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	196-199°C
Boiling Point	Not Available
Solubility	practically insoluble

Predicted Properties

Property	Value	Source
Water Solubility	0.011 g/L	ALOGPS
logP	2.53	ALOGPS
logP	2.68	ChemAxon
logS	-4.5	ALOGPS
pKa (Strongest Acidic)	5.79	ChemAxon
pKa (Strongest Basic)	-6.8	ChemAxon
Physiological Charge	-1	ChemAxon
Hydrogen Acceptor Count	5	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	109.42 Å²	ChemAxon
Rotatable Bond Count	5	ChemAxon
Refractivity	94.18 m³·mol⁻¹	ChemAxon
Polarizability	34.35 Å³	ChemAxon
Number of Rings	3	ChemAxon
Bioavailability	Yes	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	Deposition Date	View
Predicted GC-MS	Predicted GC-MS Spectrum	splash10-0005-4394000000-cee5104d5911648240f0	Not Available	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum	splash10-0h90-9486300000-ff32bbb6638456fac0ab	Not Available	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum	Not Available	Not Available	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum	Not Available	Not Available	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum	Not Available	Not Available	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum	Not Available	Not Available	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum	Not Available	Not Available	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum	Not Available	Not Available	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum	Not Available	Not Available	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum	Not Available	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-0udi-0009000000-a9c658b6227fbe717786	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-0a4r-0009000000-b7023b451fda1f0da396	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-000i-3509000000-10dd28ff6a33134ff631	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-0udi-1009000000-bb35e9834abd3581b7c9	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-0udi-2009000000-0b9b626833d64db8299c	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-0a4i-9104000000-feadec6c8ab265c3c1b3	Not Available	View Spectrum

Toxicity Profile

Mechanism of Toxicity

Acenocoumarol 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 decresed prothrombin levels and a decrease in the amount of thrombin generated and bound to fibrin. This reduces the thrombogenicity of clots. (1)

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Minimum Risk Level

Not Available

Symptoms

The onset and severity of the symptoms are dependent on the individual's sensitivity to oral anticoagulants, the severity of the overdosage, and the duration of treatment. Bleeding is the major sign of toxicity with oral anticoagulant drugs. The most frequent symptoms observed are: cutaneous bleeding (80%), haematuria (with renal colic) (52%), haematomas, gastrointestinal bleeding, haematemesis, uterine bleeding, epistaxis, gingival bleeding and bleeding into the joints. Further symptoms include tachycardia, hypotension, peripheral circulatory disorders due to loss of blood, nausea, vomiting, diarrhoea and abdominal pains.

Treatment

The primary antidote to acenocoumarol 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 acenocoumarol can affect the body for many months, and the antidote must be administered regularly for a long period of time. (7)

Toxicity Values

Toxicity Value	Unit	Value Range	Organism	Dose Descriptor	Route of Exposure	Predicted or Experimental	Reference
1470.0	mg/kg	Not Available	Mouse	LD50	Oral	experimental	T14
115.0	mg/kg	Not Available	Mouse	LD50	Intraperitoneal	experimental	T14
8653.0	Log mg/kg	[4900:15000]	Rat	LD50	oral	predicted	Not Available

Health Effects

Health Effect	Relationship	Direction	Reference

Exposure Sources

Source ID	Source	Sector	Reference
273	Antithrombotic agents	Healthcare, pharmaceuticals & veterinary products	Not Available
505	Amplifiers	Electrical & Electronic Equipment	Not Available

Pathways

3 pathways

Acenocoumarol Action Pathway

Acenocoumarol Drug Metabolism Action Pathway

Acenocoumarol Predicted Metabolism Pathway

Targets

Structure	Protein	UniProt ID	Organism	Relationship	Details
Click to view 3D structure	Vitamin K epoxide reductase complex subunit 1	Q9BQB6	Humans	Predicted (SEA)	0.155698
Click to view 3D structure	Vitamin K epoxide reductase complex subunit 1	Q6TEK4	Rattus norvegicus	Predicted (SEA)	0.311397
Click to view 3D structure	NAD(P)H dehydrogenase [quinone] 1	P05982	Rattus norvegicus	Predicted (SEA)	0.856341
Click to view 3D structure	NAD(P)H dehydrogenase [quinone] 1	P15559	Humans	Predicted (SEA)	0.778492
Click to view 3D structure	Albumin	P02768	Humans	Predicted (SEA)	47.1766
Click to view 3D structure	Endolysin	P00720	Enterobacteria phage T4	Predicted (SEA)	7.23998
Click to view 3D structure	Pol polyprotein	Q72874	Human immunodeficiency virus 1	Predicted (SEA)	59.5547
Click to view 3D structure	Vitamin K epoxide reductase complex subunit 1	Q6B4J2	Bos taurus	Predicted (SEA)	0.934191
Click to view 3D structure	Poly [ADP-ribose] polymerase tankyrase-1	O95271	Humans	Predicted (SEA)	66.9503
Click to view 3D structure	Protein phosphatase EYA3	Q99504	Humans	Predicted (SEA)	1.86838
Click to view 3D structure	Carbonic anhydrase 9	Q16790	Humans	Predicted (SEA)	359.741
Click to view 3D structure	Poly [ADP-ribose] polymerase tankyrase-2	Q9H2K2	Humans	Predicted (SEA)	64.4592
Click to view 3D structure	Carbonic anhydrase 12	O43570	Humans	Predicted (SEA)	369.083
Click to view 3D structure	Streptokinase A	P10520	Streptococcus pyogenes serotype M1	Predicted (SEA)	302.289
Click to view 3D structure	Carbonic anhydrase 1	P00915	Humans	Predicted (SEA)	457.753
Click to view 3D structure	Carbonic anhydrase 2	P00918	Humans	Predicted (SEA)	561.215
Click to view 3D structure	Long-chain-fatty-acid--CoA ligase 6	Q9UKU0	Humans	Predicted (SEA)	19.7737
Click to view 3D structure	Patatin-like phospholipase domain-containing protein 6	Q3TRM4	Mus musculus	Predicted (SEA)	41.1044
Click to view 3D structure	Mitogen-activated protein kinase 1	P28482	Humans	Predicted (SEA)	1148.67
Click to view 3D structure	G-protein coupled receptor 35	Q9HC97	Humans	Predicted (SEA)	61.2673
Click to view 3D structure	Bifunctional polynucleotide phosphatase/kinase	Q96T60	Humans	Predicted (SEA)	1.47914
Click to view 3D structure	Cytochrome P450 2C9	P11712	Humans	Predicted (SEA)	1971.84
Click to view 3D structure	Toll-like receptor 9	Q9NR96	Humans	Predicted (SEA)	69.4415
Click to view 3D structure	Poly [ADP-ribose] polymerase 1	P09874	Humans	Predicted (SEA)	169.322
Click to view 3D structure	Induced myeloid leukemia cell differentiation protein Mcl-1	Q07820	Humans	Predicted (SEA)	370.251
Click to view 3D structure	Vitamin K epoxide reductase complex subunit 1	Q9BQB6	Humans	Known	Acenocoumarol 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 decresed prothrombin levels and a decrease in the amount of thrombin generated and bound to fibrin. This reduces the thrombogenicity of clots.
Click to view 3D structure	Alpha-1-acid glycoprotein 1	P02763	Humans	Known	Acenocoumarol 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 decresed prothrombin levels and a decrease in the amount of thrombin generated and bound to fibrin. This reduces the thrombogenicity of clots.
Click to view 3D structure	Albumin	P02768	Humans	Known	Acenocoumarol 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 decresed prothrombin levels and a decrease in the amount of thrombin generated and bound to fibrin. This reduces the thrombogenicity of clots.