SynCED: Indomethacin

Record Information

Version

1.0

Creation Date

2009-07-21 20:26:37 UTC

Update Date

2026-05-14 16:35:38 UTC

Accession Number

CHEM002172

Identification

Common Name

Indomethacin

Class

Small Molecule

Description

Indomethacin is a non-steroidal antiinflammatory agent (NSAIA) with antiinflammatory, analgesic and antipyretic activity. Its pharmacological effect is thought to be mediated through inhibition of the enzyme cyclooxygenase (COX), the enzyme responsible for catalyzes the rate-limiting step in prostaglandin synthesis via the arachidonic acid pathway.

Contaminant Sources

HMDB Contaminants - Urine
STOFF IDENT Compounds
Suspected Compounds - Waste Water
Suspected Compounds – Schymanski Project
T3DB toxins
ToxCast & Tox21 Chemicals

Contaminant Type

Amide
Amine
Anti-Inflammatory Agent
Anti-Inflammatory Agent, Non-Steroidal
Cardiovascular Agent
Cyclooxygenase Inhibitor
Drug
Ester
Ether
Gout Suppressant
Metabolite
Organic Compound
Organochloride
Synthetic Compound
Tocolytic Agent

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Value	Source
1-(p-Chlorobenzoyl)-5-methoxy-2-methylindole-3-acetic acid	ChEBI
Aconip	ChEBI
Indocin	ChEBI
Indometacina	ChEBI
Indometacine	ChEBI
Indometacinum	ChEBI
{1-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methyl-1H-indol-3-yl}acetic acid	ChEBI
Indometacin	Kegg
1-(p-Chlorobenzoyl)-5-methoxy-2-methylindole-3-acetate	Generator
{1-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methyl-1H-indol-3-yl}acetate	Generator
IMN	HMDB
Indometacyna	HMDB
Indomethacine	HMDB
Indomethacinum	HMDB
Indomethancin	HMDB
Indomethazine	HMDB
Indomethine	HMDB
Indometicina	HMDB
Hydrochloride, indomethacin	HMDB
Metindol	HMDB
Osmosin	HMDB
Amuno	HMDB
Indomet 140	HMDB
Indomethacin hydrochloride	HMDB
Indocid	HMDB

Chemical Formula

C₁₉H₁₆ClNO₄

Average Molecular Mass

357.788 g/mol

Monoisotopic Mass

357.077 g/mol

CAS Registry Number

53-86-1

IUPAC Name

2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetic acid

Traditional Name

indomethacin

SMILES

COC1=CC2=C(C=C1)N(C(=O)C1=CC=C(Cl)C=C1)C(C)=C2CC(O)=O

InChI Identifier

InChI=1S/C19H16ClNO4/c1-11-15(10-18(22)23)16-9-14(25-2)7-8-17(16)21(11)19(24)12-3-5-13(20)6-4-12/h3-9H,10H2,1-2H3,(H,22,23)

InChI Key

CGIGDMFJXJATDK-UHFFFAOYSA-N

Chemical Taxonomy

Description

Belongs to the class of organic compounds known as benzoylindoles. These are organic compounds containing an indole attached to a benzoyl moiety through the acyl group.

Kingdom

Organic compounds

Super Class

Organoheterocyclic compounds

Class

Indoles and derivatives

Sub Class

Benzoylindoles

Direct Parent

Benzoylindoles

Alternative Parents

Substituents

Benzoylindole
Indole-3-acetic acid derivative
Indolecarboxylic acid derivative
Indolyl carboxylic acid derivative
4-halobenzoic acid or derivatives
Halobenzoic acid or derivatives
3-alkylindole
Indole
Benzoic acid or derivatives
Anisole
Benzoyl
Chlorobenzene
Alkyl aryl ether
Halobenzene
Benzenoid
Substituted pyrrole
Aryl chloride
Aryl halide
Monocyclic benzene moiety
Heteroaromatic compound
Pyrrole
Carboxylic acid derivative
Carboxylic acid
Ether
Azacycle
Monocarboxylic acid or derivatives
Hydrocarbon derivative
Organic oxygen compound
Carbonyl group
Organic nitrogen compound
Organopnictogen compound
Organic oxide
Organohalogen compound
Organochloride
Organonitrogen compound
Organooxygen compound
Aromatic heteropolycyclic compound

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

aromatic ether (CHEBI:49662 )
monochlorobenzenes (CHEBI:49662 )
N-acylindole (CHEBI:49662 )
indole-3-acetic acids (CHEBI:49662 )
a small molecule (CPD-10545 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Cytoplasm
Extracellular
Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Biological Roles

Chemical Roles

EC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitor

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	151°C
Boiling Point	Not Available
Solubility	0.937 mg/L (at 25°C)

Predicted Properties

Property	Value	Source
Water Solubility	0.0024 g/L	ALOGPS
logP	4.25	ALOGPS
logP	3.53	ChemAxon
logS	-5.2	ALOGPS
pKa (Strongest Acidic)	3.8	ChemAxon
pKa (Strongest Basic)	-2.3	ChemAxon
Physiological Charge	-1	ChemAxon
Hydrogen Acceptor Count	4	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	68.53 Å²	ChemAxon
Rotatable Bond Count	4	ChemAxon
Refractivity	94.81 m³·mol⁻¹	ChemAxon
Polarizability	36.64 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

Toxicity Profile

Route of Exposure

Parenteral(intravenous); enteral(rectal); oral. Bioavailability is approximately 100% following oral administration and 80-90% following rectal administration.

Mechanism of Toxicity

Antiinflammatory effects of Indomethacin are believed to be due to inhibition of cylooxygenase in platelets which leads to the blockage of prostaglandin synthesis. Antipyretic effects may be due to action on the hypothalamus, resulting in an increased peripheral blood flow, vasodilation, and subsequent heat dissipation. Indomethacin is a prostaglandin G/H synthase (also known as cyclooxygenase or COX) inhibitor that acts on both prostaglandin G/H synthase 1 and 2 (COX-1 and -2). Prostaglandin G/H synthase catalyzes the conversion of arachidonic acid to a number of prostaglandins involved in fever, pain, swelling, inflammation, and platelet aggregation. Indomethacin antagonizes COX by binding to the upper portion of the active site, preventing its substrate, arachidonic acid, from entering the active site. Indomethacin, unlike other NSAIDs, also inhibits phospholipase A2, the enzyme responsible for releasing arachidonic acid from phospholipids. Indomethacin is more selective for COX-1 than COX-2, which accounts for its increased adverse gastric effects relative to other NSAIDs. COX-1 is required for maintaining the protective gastric mucosal layer. The analgesic, antipyretic and anti-inflammatory effects of indomethacin occur as a result of decreased prostaglandin synthesis. Its antipyretic effects may be due to action on the hypothalamus, resulting in an increased peripheral blood flow, vasodilation, and subsequent heat dissipation.

Metabolism

Hepatic. Route of Elimination: Indomethacin is eliminated via renal excretion, metabolism, and biliary excretion. Half Life: 4.5 hours

Toxicity Values

LD50: 50 mg/kg (oral, mice) (based on 14 day mortality response) LD50: 12 mg/kg (oral, rat) (based on 14 day mortality response)

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

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

Uses/Sources

For moderate to severe rheumatoid arthritis including acute flares of chronic disease, ankylosing spondylitis, osteoarthritis, acute painful shoulder (bursitis and/or tendinitis) and acute gouty arthritis.

Minimum Risk Level

Not Available

Health Effects

Not Available

Symptoms

The following symptoms may be observed following overdosage: nausea, vomiting, intense headache, dizziness, mental confusion, disorientation, or lethargy. There have been reports of paresthesias, numbness, and convulsions.

Treatment

Treatment is symptomatic and supportive. The stomach should be emptied as quickly as possible if the ingestion is recent. If vomiting has not occurred spontaneously, the patient should be induced to vomit with syrup of ipecac. If the patient is unable to vomit, gastric lavage should be performed. Once the stomach has been emptied, 25 or 50 g of activated charcoal may be given. Depending on the condition of the patient, close medical observation and nursing care may be required. The patient should be followed for several days because gastrointestinal ulceration and hemorrhage have been reported as adverse reactions of indomethacin. Use of antacids may be helpful. (8)

Concentrations