DrugBank: Phenindione (DB00498)

targets (1)

Identification

Name

Phenindione

Accession Number

DB00498 (APRD00166)

Type

small molecule

Groups

approved

Description

An indandione that has been used as an anticoagulant. Phenindione has actions similar to warfarin, but it is now rarely employed because of its higher incidence of severe adverse effects. (From Martindale, The Extra Pharmacopoeia, 30th ed, p234)

Structure

Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure

Synonyms

Not Available

Brand names

Athrombon
Bindan
Cronodione
Danedion
Danilon
Danilone
Diadilan
Dindevan
Dineval
Diophindane
Emandion
Emandione
Eridione
Fenhydren
Fenilin
Fenindion
Hedulin
Hemolidione
Indema
Indion
Indon
Phenhydren
Phenillin
Phenylen
Phenylin
Phenylindanedione
Phenylindione
Phenyline
Phenyllin
PID
Pindione
Rectadione
Theradione
Thrombasal
Tromazal
Trombol

Brand name mixtures

Not Available

Categories

Anticoagulants

CAS number

83-12-5

Weight

Average: 222.2387
Monoisotopic: 222.068079564

Chemical Formula

C₁₅H₁₀O₂

InChI Key

InChIKey=NFBAXHOPROOJAW-UHFFFAOYSA-N

InChI

InChI=1S/C15H10O2/c16-14-11-8-4-5-9-12(11)15(17)13(14)10-6-2-1-3-7-10/h1-9,13H

Plain Text

IUPAC Name

2-phenyl-2,3-dihydro-1H-indene-1,3-dione

SMILES

O=C1C(C(=O)C2=C1C=CC=C2)C1=CC=CC=C1

Plain Text

Mass Spec

Not Available

Taxonomy

Kingdom

Organic

Classes

Indanes

Substructures

Indanes
Benzene and Derivatives
Aromatic compounds
Benzoyl Derivatives
Ketones

Pharmacology

Indication

For the treatment of pulmonary embolism, cardiomyopathy, atrial fibrillation and flutter, cerebral embolism, mural thrombosis, and thrombophili. Also used for anticoagulant prophylaxis.

Pharmacodynamics

Phenindione thins the blood by antagonizing vitamin K which is required for the production of clotting factors in the liver. Anticoagulants such as Phenindione have no direct effect on an established thrombus, nor do they reverse ischemic tissue damage (damage caused by an inadequate blood supply to an organ or part of the body). However, once a thrombus has occurred, the goal of anticoagulant treatment is to prevent further extension of the formed clot and prevent secondary thromboembolic complications which may result in serious and possibly fatal sequelae. Phenindione has actions similar to warfarin, but it is now rarely employed because of its higer incidence of severe adverse effects.

Mechanism of action

Phenindione 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.

Absorption

Absorbed slowly from the gastrointestinal tract.

Volume of distribution

Not Available

Protein binding

88%

Metabolism

Hepatic.

Route of elimination

Not Available

Half life

5-10 hours

Clearance

Not Available

Toxicity

Oral, mouse: LD50 = 175 mg/kg; Oral, rat: LD50 = 163 mg/kg.

Affected organisms

Humans and other mammals

Pathways

Not Available

Pharmacoeconomics

Manufacturers

Sanofi aventis us llc

Packagers

Not Available

Dosage forms

Not Available

Prices

Not Available

Patents

Not Available

Properties

State

solid

Melting point

148-151 oC

Experimental Properties

Property	Value	Source
water solubility	27 mg/L (at 20 oC)	PhysProp
logP	2.6	PhysProp

Predicted Properties

Property	Value	Source
water solubility	2.30e-02 g/l	ALOGPS
logP	3.10	ALOGPS
logP	2.88	ChemAxon Molconvert
logS	-3.98	ALOGPS
pKa		ChemAxon Molconvert
hydrogen acceptor count	2	ChemAxon Molconvert
hydrogen donor count	0	ChemAxon Molconvert
polar surface area	34.14	ChemAxon Molconvert
rotatable bond count	1	ChemAxon Molconvert
refractivity	65.23	ChemAxon Molconvert
polarizability	23.24	ChemAxon Molconvert

References

Synthesis Reference

Not Available

General Reference

Link

External Links

Resource	Link
KEGG Compound	C07584
PubChem Compound	4760
PubChem Substance	46505018
ChemSpider	4596
ChEBI	8066
ChEMBL	8066
Therapeutic Targets Database	DAP000769
Drug Product Database	0
Wikipedia	http://en.wikipedia.org/wiki/Phenindione

ATC Codes

B01AA02

AHFS Codes

Not Available

PDB Entries

Not Available

FDA label

Not Available

MSDS

show (62.6 KB)

Interactions

Drug Interactions

Drug	Interaction

Food Interactions

Not Available

Targets
1. Vitamin K epoxide reductase complex subunit 1 Pharmacological action: yes Actions: inhibitor Involved in vitamin K metabolism. Catalytic subunit of the vitamin K epoxide reductase (VKOR) complex which reduces inactive vitamin K 2,3-epoxide to active vitamin K Organism class: human UniProt ID: Q9BQB6 Gene: VKORC1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed Mentre F, Pousset F, Comets E, Plaud B, Diquet B, Montalescot G, Ankri A, Mallet A, Lechat P: Population pharmacokinetic-pharmacodynamic analysis of fluindione in patients. Clin Pharmacol Ther. 1998 Jan;63(1):64-78. Pubmed Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

Targets

1. Vitamin K epoxide reductase complex subunit 1

Pharmacological action: yes
Actions: inhibitor

Involved in vitamin K metabolism. Catalytic subunit of the vitamin K epoxide reductase (VKOR) complex which reduces inactive vitamin K 2,3-epoxide to active vitamin K

Organism class: human
UniProt ID: Q9BQB6 Link_out

Gene: VKORC1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
Mentre F, Pousset F, Comets E, Plaud B, Diquet B, Montalescot G, Ankri A, Mallet A, Lechat P: Population pharmacokinetic-pharmacodynamic analysis of fluindione in patients. Clin Pharmacol Ther. 1998 Jan;63(1):64-78. Pubmed
Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

Comments

Drug created on June 13, 2005 07:24 / Updated on November 10, 2010 13:40

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.