Etoricoxib

Base Information

• Chemical Name: Etoricoxib
• CAS No.: 202409-33-4
• Molecular Formula: C18H15ClN2O2S
• Molecular Weight: 358.848
• Hs Code.: 2933399090
• European Community (EC) Number: 682-421-5
• UNII: WRX4NFY03R
• DSSTox Substance ID: DTXSID3046457
• Nikkaji Number: J1.126.176K
• Wikipedia: Etoricoxib
• Wikidata: Q631202
• NCI Thesaurus Code: C52188
• Pharos Ligand ID: TA1UDKMSS5Y2
• Metabolomics Workbench ID: 43612
• ChEMBL ID: CHEMBL416146
• Mol file: 202409-33-4.mol

Synonyms:Arcoxia;etoricoxib;L 791456;L-791456;L791456;MK 0663;MK-0663;MK0663

Chemical Property of Etoricoxib

Chemical Property:

• Appearance/Colour: off-white powder
• Vapor Pressure: 5.17E-10mmHg at 25°C
• Melting Point: 134-135 °C
• Refractive Index: 1.6
• Boiling Point: 510 °C at 760 mmHg
• PKA: 4.5(at 25℃)
• Flash Point: 262.2 °C
• PSA: 68.30000
• Density: 1.298 g/cm³
• LogP: 5.25670
• Storage Temp.: -20°C Freezer
• XLogP3: 3.3
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 3
• Exact Mass: 358.0542766
• Heavy Atom Count: 24
• Complexity: 514

Purity/Quality:

99%min ^*data from raw suppliers

Etoricoxib ^*data from reagent suppliers

Safty Information:

• Pictogram(s): T
• Hazard Codes: T
• Statements: 22-24
• Safety Statements: 36/37-45

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC1=NC=C(C=C1)C2=C(C=C(C=N2)Cl)C3=CC=C(C=C3)S(=O)(=O)C
• Recent ClinicalTrials: Fixed-dose Combination of Etoricoxib + Cyclobenzaprine for Pain Relief After Third Molar Extraction in Brazil
• Recent EU Clinical Trials: Comparison of the preventive painkiller effect of etoricoxib and celecoxib after M3M surgery: A randomized, double-masked clinical trial
• Drug Interactions: Warfarin: long-term usage of warfarin therapy in patients with stable efficacy. Daily application of this drug should be 120mg with the prothrombin time being approximately 13% higher than the international normalized ratio (INR). Rifampicin: Rifampicin is a strong inducer of hepatic metabolism. The combination of this product with rifampicin allows the plasma area under the curve (AUC) to be reduced by 65%. Therefore when this product is combined with rifampin, we should take into account their interaction. Methotrexate: When using this product at a dose greater than 90mg/day as well as being in combination with methotrexate, you should consider monitoring the toxicity associated with methotrexate. Diuretics, angiotensin-converting enzyme (ACE) inhibitors and angiotensin II antagonists (AIIAs): Non-steroidal anti-inflammatory drugs, including selective cyclooxygenase-2 inhibitors can reduce the antihypertensive effect of the diuretics, angiotensin converting inhibitors and angiotensin II antagonists. Lithium salt: non-selective non-steroidal anti-inflammatory drugs and cyclooxygenase-2 selective inhibitors may increase plasma levels of lithium salts. Aspirin: It can be used simultaneously with a lose-dose aspirin for the prevention of cardiovascular events. However, upon being in combination with low-dose aspirin, the incidence of gastrointestinal ulcers or other complication rate is higher than in the case of single usage of this product. Oral contraceptives: upon selecting suitable oral contraceptives for being used in combination with this product, we need to take into account of the increase of the EE concentration. The increase of the EE concentration will increase the incidence of the related adverse events of oral contraceptives (such as the risk of venous thromboembolism for women). Other: Antacids and ketoconazole (CYP3A4 strong inhibitors) do not produce clinically significant impact on the pharmacokinetics of this product.
• Indications: 1. the treatment of OA: the good has a comparable effect as celecoxib, ibuprofen with similar efficacy with large doses of diclofenac and naproxen. 2. acute gouty arthritis: This product is 120 mg/d and can quickly and effectively relieve pain, and has a similar efficacy as the gold standard drug indomethacin in the treatment of gouty arthritis with a better tolerance and a lower incidence of drug-related adverse events than indomethacin. 3. ankylosing spondylitis: etoricoxib has a similar efficacy as naproxen taken twice per day; etoricoxib has a better effect in treating secondary end-point aspects such as alleviating night pain, inflammation, functionality and flexibility. 4. rheumatoid arthritis: large-scale, controlled clinical trial results showed that etoricoxib taken once daily has a better efficacy compared to naproxen taken twice daily with a better tolerance in patients. 5. osteoarthritis: This product (once/day) has a comparable efficacy as celecoxib (once/day), and ibuprofen (3 times/day); and it (once/day) has a similar efficacy with high-dose diclofenac (3 times/day) and naproxen (3 times/day). 6. postoperative dental pain: compared with acetaminophen/codeine and oxycodone/ p-acetaminophen, taking etoricoxib once daily can yield a better efficacy in alleviating the pain feeling of patients. 7. chronic low back pain: compare this product with Placebo on the treatment efficacy of chronic low back pain in 12 weeks has demonstrated that the clinical efficacy of this product was significantly superior to placebo drug with being effective in the treatment for only one week while the effect is very significant in four weeks and the sustained effect being able to reach over three months. 8. for controlling late pain of postoperative thyroid: when thyroid operation patients orally take etoricoxib at 1 h before operation can reduce the oral administrated dose of oxycodone acetaminophen at 6~12 h after surgery in patients.
• Description: Etoricoxib is a COX-2 inhibitor developed as a follow-up of rofecoxib for the treatment of osteoarthritis, rheumatoid arthritis, dysmenorrhoea, gout, ankylosing spondylitis and pain. Several processes describe the preparation of etoricoxib in 4 or 5 steps from 6- methylnicotinate. The key step is the novel pyridine construction using annulation of a ketosutfone with a vinamidinium synthon. In human whole blood, in vitro, the IC50 value obtained for inhibition of COX-2 is 1 .I μM as compared to 116 μM obtained for inhibition of COX-1. Thus, etoricoxib is the most selective COX-2 inhibitor to date, with a COX-IKOX- 2 ratio of IC50 values of 106 for etoricoxib as compared to 35, 30, 7.6 for rofecoxib, valdecoxib and celecoxib, respectively. Its in vivo potency is generally comparable to that of rofecoxib in animal models against inflammation (carrageenan-induced paw edema), pyrexia (LPS-induced pyresis), pain (carrageenan-induced hyperalgesia) and arthritis (adjuvant-induced arthritis). Etoricoxib is well tolerated with dose-proportional pharmacokinetics. It has no effect on bleeding time or platelet ag regation. The gastrointestinal tolerability of etoricoxib is excellent as demonstrated by [51Cr] models of excretion in rats and squirrel monkeys. Moreover, etoricoxib, unlike naproxen is not associated with significant inhibition of gastric mucosal PGE2 synthesis compared to placebo. Etoricoxib is highly absorbed, has a tmax of 1.5 h and a half-life time of approximately 15-22h. Five metabolites, weak inhibitors of COX-1 and COX-2 have been identified after renal excretion. Finally, although multiple CYP enzymes are involved in the metabolism of etoricoxib (CYP3A4 being the major contributor), etoricoxib is not a potent CYP3A4 inhibitor or inducer. In patients undergoing molar extraction, etoricoxib showed similar efficacy to naproxen sodium with a longer duration of analgesia than acetaminophen/codeine (approximately ＞24 h, 22 h and 5.2 h, respectively) and a better total pain relief score over 8 h. Similar efficacy of etoricoxib and naproxen was also seen in patients suffering of osteoarthritis. In the treatment of rheumatoid arthritis and ankylosing spondylitis, etoricoxib demonstrated significantly superior efficacy compared to naproxen and placebo. Etoricoxib did not affect the pharmacokinetics of prednisolone (i.v. or p.0.) and its co-administration with antacids showed insignificant effects on the maximal concentration and its absorption. .
• Uses: A specific inhibitor of COX-2 . anti-inflammatory, analgesic;cyclooxygenase inhibitor For the treatment of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, chronic low back pain, acute pain and gout. Labeled Etoricoxib, intended for use as an internal standard for the quantification of Etoricoxib by GC- or LC-mass spectrometry. Etoricoxib is a dipyridinyl compound that demonstrates high in vitro and ex vivo selectivity for COX-2 over COX-1 in several assays, e.g., in the production of PGE2 by CHO cells expressing either COX-2 (IC50 = 79 nM) or COX-1 (IC50 > 50 μM). Oral etoricoxib is well absorbed and metabolized extensively via oxidation, with metabolites excreted largely in the urine.[Cayman Chemical]
• Clinical Use: Etoricoxib is a selective COX-2 inhibitor being developed for postsurgical treatment of dental pain (120 mg) and osteoarthritis. It has a methylsulfonyl group common to the other coxib inhibitors.
• 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; concentration reduced by rifampicin. 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 venlaflaxine. Antidiabetic agents: effects of sulphonylureas enhanced. Antiepileptics: possibly increased phenytoin concentration. Antivirals: increased risk of haematological toxicity with zidovudine; concentration possibly increased by ritonavir. Ciclosporin: may potentiate nephrotoxicity Cytotoxics: reduced excretion of methotrexate; possibly reduced excretion of pemetrexed; 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 bleeding. Tacrolimus: increased risk of nephrotoxicity.

Technology Process of Etoricoxib

There total 62 articles about Etoricoxib 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: 96.5%

etoricoxib hydrochloride (202409-40-3) → etoricoxib (202409-33-4)

Guidance literature:

With sodium hydrogencarbonate; In dichloromethane; water; at 10 - 20 ℃; for 0.5h; Reagent/catalyst; Large scale;

Reference yield: 95.0%

4-(5-chloro-6'-methyl-[2,3'-bipyridin]-3-yl)benzenesulfinic acid + methyl iodide (74-88-4) → etoricoxib (202409-33-4)

Guidance literature:

4-(5-chloro-6'-methyl-[2,3'-bipyridin]-3-yl)benzenesulfinic acid; With tetra-(n-butyl)ammonium iodide; In tetrahydrofuran; at 65 ℃; for 0.333333h;

methyl iodide; In tetrahydrofuran; at 65 ℃; for 2h; Cooling with liquid nitrogen;

DOI:10.1021/acs.orglett.6b02723

Reference yield: 94.0%

5-chloro-3-(4-methylsulphonyl)phenyl-2-(2-methyl-5-pyridinyl)pyridine (292067-97-1) → etoricoxib (202409-33-4)

Guidance literature:

With sodium molybdate; sulfuric acid; dihydrogen peroxide; In methanol; at 55 ℃; for 0.25h;

upstream raw materials:

2,5-dichloro-3-[4-(methylsulfonyl)phenyl]pyridine

1-(6-methyl-3-pyridinyl)-2-[4-(methylsulfonyl)phenyl]ethanone

2,3-dichloroacrolein

2-methyl-5-formylpyridine

Downstream raw materials:

Etoricoxib-1'-N-Oxide

6'-Carboxyetoricoxib

Refernces

• 1、 Liu, Kai-Jian,Wang, Zheng,Lu, Ling-Hui,Chen, Jin-Yang,Zeng, Fei,Lin, Ying-Wu,Cao, Zhong,Yu, Xianyong,He, Wei-Min. "Synergistic cooperative effect of CF3SO2Na and bis(2-butoxyethyl)ether towards selective oxygenation of sulfides with molecular oxygen under visible-light irradiation". . p. 496 - 500. Retrieved 2021/01/28.
• 2、 Ni, Shengjun,Hribersek, Matic,Baddigam, Swarna K.,Ingner, Fredric J. L.,Orthaber, Andreas,Gates, Paul J.,Pilarski, Lukasz T.. "Mechanochemical Solvent-Free Catalytic C?H Methylation". supporting information. p. 6660 - 6666. Retrieved 2020/12/18.