Indomethacin

Base Information

• Chemical Name: Indomethacin
• CAS No.: 53-86-1
• Deprecated CAS: 37242-43-6,91853-74-6,503560-73-4,503560-73-4,91853-74-6
• Molecular Formula: C19H16ClNO4
• Molecular Weight: 357.793
• Hs Code.: 29339900
• European Community (EC) Number: 200-186-5
• NSC Number: 757061
• UN Number: 2811
• UNII: XXE1CET956
• DSSTox Substance ID: DTXSID9020740
• Nikkaji Number: J1.368D
• Wikipedia: Indometacin
• Wikidata: Q409231
• NCI Thesaurus Code: C576
• RXCUI: 5781
• Pharos Ligand ID: AC3D4RL6RU1S
• Metabolomics Workbench ID: 42712
• ChEMBL ID: CHEMBL6
• Mol file: 53-86-1.mol

Synonyms:Amuno;Indocid;Indocin;Indomet 140;Indometacin;Indomethacin;Indomethacin Hydrochloride;Metindol;Osmosin

Chemical Property of Indomethacin

Chemical Property:

• Appearance/Colour: White crystalline powder
• Vapor Pressure: 8.61E-11mmHg at 25°C
• Melting Point: 155-162 °C
• Refractive Index: 1.6800 (estimate)
• Boiling Point: 499.363 °C at 760 mmHg
• PKA: 4.5(at 25℃)
• Flash Point: 255.806 °C
• PSA: 68.53000
• Density: 1.327 g/cm³
• LogP: 3.92730
• Storage Temp.: Store at RT
• Sensitive.: Light Sensitive
• Solubility.: ethanol: 50 mg/mL, clear, yellow-green
• Water Solubility.: Soluble in acetone (40 mg/mL - clear, yellow solution), ethanol (20 mg/mL), ether, castor oil; Soluble in chloroform (50 mg/mL -
• XLogP3: 4.3
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 4
• Exact Mass: 357.0767857
• Heavy Atom Count: 25
• Complexity: 506
• Transport DOT Label: Poison

Purity/Quality:

99%, ^*data from raw suppliers

Indomethacin ^*data from reagent suppliers

Safty Information:

• Pictogram(s): T+, Xi
• Hazard Codes: T+,Xi,T
• Statements: 28-36/37/38-39/23/24/25-23/24/25
• Safety Statements: 28-36/37-45-36-26

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Nonsteroidal Antiinflammatory Drugs
• Canonical SMILES: CC1=C(C2=C(N1C(=O)C3=CC=C(C=C3)Cl)C=CC(=C2)OC)CC(=O)O
• Recent ClinicalTrials: Trial of Indomethacin in Chronic Pancreatitis
• Recent EU Clinical Trials: PROPHYLAXIS OF POST-ERCP ACUTE PANCREATITIS: A RANDOMISED, MULTICENTRE, OPEN-LABEL STUDY COMPARING INDOMETHACIN VERSUS INDOMETHACIN AND RINGER LACTATE COMBINATION
• Recent NIPH Clinical Trials: Prospective trial on the safety of rectal indomethacin 100mg for prophylaxis of post endoscopic retrograde cholangiopancreatography pancreatitis for Japanese.
• Uses: 1.The product is anti-inflammatory, and antipyretic effect is obvious, mainly is used for salicylates to tolerance or the effect is not significant rheumatism and arthritis, ankylosing light spondylitis, osteoarthritis. 2.Non steroid anti-inflammatory analgesic Indomethacin is used in rheumatoid arthritis, nonspecific infectious polyarthritis, gouty arthritis, osteoarthritis, ankylosing spondylitis, arthrosis, back pain, neuralgia, myalgia, and other diseases accompanied by inflammation. Inhibits cyclooxygenase (IC50=0.1uM) selectively over liposygenases (IC50=100uM for 5-,12- and 15-LO). A clinically useful NAISD antiinflammatory, antipyretic, analgesic
• Description: Aqueous solutions of indomethacin are not stable because of the ease of hydrolysis of the p-chlorobenzoyl group. The original synthesis of indomethacin by Shen et al. involved the formation of 2-methyl-5-methoxyindole acetic acid and subsequent acylation after protection of the carboxyl group as the t-butyl ester. It was introduced in the United States in 1965. It is still one of the most potent NSAIDs in use. It also is a more potent antipyretic than either aspirin or acetaminophen, and it possesses approximately 10 times the analgetic potency of aspirin.
• Indications: Indomethacin (Indocin) is used in the treatment of acute gouty arthritis, rheumatoid arthritis, ankylosing spondylitis, and osteoarthritis. It is not recommended for use as a simple analgesic or antipyretic because of its potential for toxicity.While indomethacin inhibits both COX-1 and COX-2, it is moderately selective for COX- 1. It produces more CNS side effects than most of the other NSAIDs. Severe headache occurs in 25 to 50% of patients; vertigo, confusion, and psychological disturbances occur with some regularity. GI symptoms also are more frequent and severe than with most other NSAIDs. Hematopoietic side effects (e.g., leukopenia, hemolytic anemia, aplastic anemia, purpura, thrombocytopenia, and agranulocytosis) also may occur. Ocular effects (blurred vision, corneal deposits) have been observed in patients receiving indomethacin, and regular ophthalmological examinations are necessary when the drug is used for long periods. Hepatitis, jaundice, pancreatitis, and hypersensitivity reactions also have been noted.
• Therapeutic Function: Antiinflammatory
• Biological Functions: Indomethacin (Indocin) is an acetic acid derivative related functionally to sulindac (Clinoril), a prodrug with a long half-life, and etodolac (Lodine).They are metabolized in the liver and excreted as metabolites in the bile and via the kidney. They are potent inhibitors of COX and thus extremely effective antiinflammatory agents.
• Clinical Use: Indomethacin is available for the short-term treatment of acute gouty arthritis, acute pain of ankylosing spondylitis, and osteoarthritis. An injectable form to be reconstituted also is available as the sodium trihydrate salt for IV use in premature infants with patent ductus arteriosus. Because of its ability to suppress uterine activity by inhibiting prostaglandin biosynthesis, indomethacin also has an unlabeled use to prevent premature labor.
• Drug interactions: Potentially hazardous interactions with other drugs ACE inhibitors and angiotensin-II antagonists: antagonism of hypotensive effect; increased risk of nephrotoxicity and hyperkalaemia. Analgesics: avoid concomitant use of 2 or more NSAIDs, including aspirin (increased side effects); avoid with ketorolac (increased risk of side effects and haemorrhage). Antibacterials: possibly increased risk of convulsions with quinolones. Anticoagulants: effects of coumarins and phenindione enhanced; possibly increased risk of bleeding with heparins, dabigatran and edoxaban - avoid long term use with edoxaban. Antidepressants: increased risk of bleeding with SSRIs and venlaflaxine. Antidiabetic agents: effects of sulphonylureas enhanced. Antiepileptics: effects of phenytoin enhanced. Antipsychotics: possible severe drowsiness with haloperidol. Antivirals: increased risk of haematological toxicity with zidovudine; concentration possibly increased by ritonavir. Ciclosporin: increased risk of nephrotoxicity. Cytotoxics: reduced excretion of methotrexate. Diuretics: increased risk of nephrotoxicity, hyperkalaemia with potassium-sparing diuretics; antagonism of diuretic effect. Lithium: lithium excretion reduced. Pentoxifylline: possibly increased risk of bleeding. Probenecid: excretion of indometacin reduced. Tacrolimus: increased risk of nephrotoxicity.

Technology Process of Indomethacin

There total 87 articles about Indomethacin which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 99.0%

indomethacin ethyl ester (16401-99-3) → [1-(4-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]acetic acid (53-86-1)

Guidance literature:

With sodium hydroxide; In methanol; water; for 1h; Reflux;

DOI:10.1002/anie.201804779

Reference yield: 98.4%

2-(1-(4-chlorobenzoyl)-6-methoxy-2-methyl-1H-indol-3-yl)-1-(2-methoxyindolizin-3-yl)ethan-1-one → [1-(4-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]acetic acid (53-86-1)

Guidance literature:

With methylene blue; In water; acetonitrile; at 20 ℃; for 0.0333333h; Irradiation; Inert atmosphere; Darkness;

DOI:10.1021/acs.joc.1c01244

Reference yield: 97.0%

5-Methoxy-2-methylindole-3-acetic acid (2882-15-7) + 4-chloro-benzoyl chloride (122-01-0) → [1-(4-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]acetic acid (53-86-1)

Guidance literature:

5-Methoxy-2-methylindole-3-acetic acid; With potassium tert-butylate; In tetrahydrofuran; at -78 ℃; for 1h; Large scale;

4-chloro-benzoyl chloride; In tetrahydrofuran; at 20 ℃; for 16h; Large scale;

DOI:10.1002/adsc.201701512

upstream raw materials:

1-(4-Chlorbenzoyl)-5-methoxy-2-methyl-1H-indolyl-3-essigsaeure-2-oxo-propylester

2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indole-3-acetoxy]-2'-hydroxy-diethyloxide

5-Methoxy-2-methylindole-3-acetic acid

4-chloro-benzoyl chloride

Downstream raw materials:

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

1H-indole-3-acetic acid, 1-(4-chlorobenzoyl)-5-methoxy-2-methyl 2-(4-benzyl-1-piperazinyl)ethyl ester

indomethacin methyl ester

1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indole-3-carbaldehyde

Refernces

• 1、 Bull, Steven D.,Gardiner, Jordan E.,James, Tony D.,Kim, Hwan Myung,Odyniec, Maria L.,Park, Sang-Jun,Sedgwick, Adam C.,Webb, Emily C.,Yoon, Juyoung. "A fluorescent ESIPT-based benzimidazole platform for the ratiometric two-photon imaging of ONOO-: In vitro and ex vivo". . p. 7329 - 7334. Retrieved 2020.
• 2、 Watanabe, Kenji,Terao, Nodoka,Niwa, Takashi,Hosoya, Takamitsu. "Direct 3-Acylation of Indolizines by Carboxylic Acids for the Practical Synthesis of Red Light-Releasable Caged Carboxylic Acids". . p. 11822 - 11834. Retrieved 2021/07/31.
• 3、 -. "Synthesis method of indometacin and analogues thereof". . . Retrieved 2020/04/29.