Etodolac

Base Information

• Chemical Name: Etodolac
• CAS No.: 41340-25-4
• Molecular Formula: C17H21NO3
• Molecular Weight: 287.359
• Hs Code.: 29349990
• European Community (EC) Number: 629-689-1
• NSC Number: 757821,282126
• UNII: 2M36281008
• DSSTox Substance ID: DTXSID9020615
• Nikkaji Number: J16.541G
• Wikipedia: Etodolac
• Wikidata: Q2465218
• NCI Thesaurus Code: C47526
• RXCUI: 24605
• Pharos Ligand ID: 4AW6LZUN51DL
• Metabolomics Workbench ID: 145483
• ChEMBL ID: CHEMBL622
• Mol file: 41340-25-4.mol

Synonyms:(1,8-Diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indol-1-yl)acetic acid;1,3,4,9-Tetrahydro-1,8-diethylpyrano(3,4-b)indole-1-acetic acid;Prestwick_209;Pyrano(3,4-b)indole-1-acetic acid, 1,8-diethyl-1,3,4,9-tetrahydro-;Lodine;Lodine (TN);Ultradol;{Pyrano[3,} 4-b]indole-1-acetic acid, 1,8-diethyl-1,3,4,9-tetrahydro-;{1,8-Diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indole-1-acetic} acid;Etodolacum [INN-Latin];1,8-Diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indole-1-acetic acid;Etodolaco [INN-Spanish];Pyrano(3,4-b)indole-1-acetic acid, 1,3,4,9-tetrahydro-1,8-diethyl-;Pyrano[3,4-b]indole-1-acetic acid,1,8-diethyl-1,3,4,9-tetrahydro-;Etodolac (JAN/USP);Etodolic acid;AY 24236;Etodolac Acid;

Chemical Property of Etodolac

Chemical Property:

• Appearance/Colour: crystalline solid
• Melting Point: 145-148 °C
• Boiling Point: 507.9 °C at 760 mmHg
• PKA: 4.65(at 25℃)
• Flash Point: 260.9 °C
• PSA: 62.32000
• Density: 1.193 g/cm³
• LogP: 3.38300
• Storage Temp.: 2-8°C
• Solubility.: Practically insoluble in water, freely soluble in acetone and in ethanol (96 per cent)
• Water Solubility.: 40mg/L(37 oC)
• XLogP3: 2.8
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 4
• Exact Mass: 287.15214353
• Heavy Atom Count: 21
• Complexity: 400

Purity/Quality:

98.0%~102% ^*data from raw suppliers

Etodolac ^*data from reagent suppliers

Safty Information:

• Pictogram(s): T, Xi
• Hazard Codes: T,Xi
• Statements: 23/24/25-40-36-25-36/37/38
• Safety Statements: 22-36-45-26-36/37

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Nonsteroidal Antiinflammatory Drugs
• Canonical SMILES: CCC1=C2C(=CC=C1)C3=C(N2)C(OCC3)(CC)CC(=O)O
• Recent ClinicalTrials: A Study Comparing Perioperative Stress Reduction vs. Standard of Care in Ovarian Cancer (PRESERVE)
• Recent EU Clinical Trials: A Randomized, Multi-Center, Phase II Study to Investigate the Safety and Efficacy of SDX-101 (R-etodolac) in Combination with Chlorambucil, and that of Chlorambucil alone, in Patients with Chronic Lymphocytic Leukemia (CLL)
• Recent NIPH Clinical Trials: Is there a difference in recurrence of knee pain between the Mechanical Diagnosis and Therapy and drag intervention: randomized controlled trial
• Uses: (1) The non-steroidal anti-inflammatory drugs of Indole acetic acid class has the analgesic and anti-inflammatory effect. It can inhibit prostaglandin synthesis at the site of inflammation selectively. The product can be absorbed rapidly and has no signs of drug savings. It can be used for the treatment of rheumatoid arthritis, rheumatoid arthritis, osteoarthritis and postoperative pain relief etc. It is a medicament that suitable for elderly patients. (2) Using as anti-inflammatory drugs. betaadrenergic agonist Etodolac is a non-steroidal anti-inflammatory drug (NSAID) that selectively inhibits cyclooxygenase-2 (COX-2). Etodolac displays anti-inflammatory effects in both adjuvant arthritic and normal rats. E todolac is an anti-inflammatory; analgesic. For acute and long-term management of signs and symptoms of osteoarthritis and rheumatoid arthritis, as well as for the management of pain. Etodolac is a non-steroidal anti-inflammatory drug (NSAID). Product Data Sheet
• Production method: The acylation reaction of o-ethyl aniline, chloral hydrate and hydroxylamine can form the oxime, after the cyclization by using the sulfuric as the catalyst and the reduction by lithium aluminium hydride , oxime can turn into the indole derivatives. The reaction with the oxalyl chloride and ethanol can bring 1,2-carbonyl side chain in 3 bit and then be restored to hydroxyethyl by lithium aluminium hydride, after the condensation , cyclization with? ethyl propionylacetate and hydrolyzation. The final product-etodolac can be obtained.
• Description: Etodolac (etodolic acid) is a non-steroidal antiinflammatory/analgesic agent useful in the treatment of various inflammatory conditions, including rheumatoid and osteoarthritis.
• Indications: Etodolac (Lodine) is indicated for the treatment of osteoarthritis, rheumatoid arthritis, and acute pain. It inhibits COX-2 with slightly more selectivity than COX-1 and therefore produces less GI toxicity than many other NSAIDs. Common adverse effects include skin rashes and CNS effects.
• Clinical Use: Etodolac is promoted as the first of a new chemical class of anti-inflammatory drugs, the pyranocarboxylic acids. Although not strictly an arylacetic acid derivative (because there is a two-carbon atom separation between the carboxylic acid function and the hetero-aromatic ring), it still possesses structural characteristics similar to those of the heteroarylacetic acids and is classified here. It was introduced in the United States in 1991 for acute and long-term use in the management of osteoarthritis and as an analgetic. It also possesses antipyretic activity. Etodolac is marketed as a racemic mixture, although only the S-(+)-enantiomer possesses anti-inflammatory activity in animal models. Etodolac also displays a high degree of enantioselectivity in its inhibitory effects on the arachidonic acid cyclooxygenase system.
• Drug interactions: Potentially hazardous interactions with other drugs ACE inhibitors and angiotensin-II antagonists: antagonism of hypotensive effect, increased risk of nephrotoxicity and hyperkalaemiaAnalgesics: 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 heparin, dabigatran and edoxaban - avoid long term use with edoxaban.Antidepressants: increased risk of bleeding with SSRIs and venlafaxine.Antidiabetic agents: effects of sulphonylureas enhanced.Antiepileptics: possibly increased phenytoin concentration.Antivirals: increased risk of haematological toxicity with zidovudine; concentration possibly increased by ritonavirCiclosporin: may potentiate nephrotoxicityCytotoxic agents: reduced excretion of methotrexate; increased risk of bleeding with erlotinib.Diuretics: increased risk of nephrotoxicity; antagonism of diuretic effect; hyperkalaemia with potassium-sparing diuretics.Lithium: excretion decreased.Pentoxifylline: increased risk of bleedingTacrolimus: increased risk of nephrotoxicity.

Technology Process of Etodolac

There total 7 articles about Etodolac 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:

(R)-etodolac (87226-41-3) + (S)-etodolac (87249-11-4) → etodolac (41340-25-4)

Guidance literature:

With tin(IV) chloride; In dichloromethane; at 20 ℃; for 2h;

Reference yield:

(R)-etodolac (87226-41-3) → etodolac (41340-25-4)

Guidance literature:

With tin(IV) chloride; In tetrahydrofuran; dichloromethane; for 4h; Heating / reflux;

Reference yield:

(S)-etodolac (87249-11-4) → etodolac (41340-25-4)

Guidance literature:

sulfuric acid; In isopropyl alcohol; at 20 ℃; for 4 - 18h; Product distribution / selectivity;

upstream raw materials:

7-ethyl-2-(1H-indol-3-yl)ethan-1-ol

ethyl propanoylacetate

(R)-etodolac

(S)-etodolac

Downstream raw materials:

1,8-diethyl-4-oxo-1,3,4,9-tetrahydropyrano[3,4-b]-indole-1-acetic acid

(R)-etodolac

(S)-etodolac

(1,8-diethyl-1,3,4,9-tetrahydro-pyrano[3,4-b]indol-1-yl)-acetic acid 2-methoxy-4-[(8-methyl-nonanoylamino)-methyl]-phenyl ester

Refernces

• 1、 -. "Direct racemization of indole derivatives". Page/Page column 10. . Retrieved 2008/06/13.
• 2、 -. "Process for the resolution of etodolac using glucamine derivatives". . . Retrieved 2008/06/13.