Lumiracoxib

Base Information

• Chemical Name: Lumiracoxib
• CAS No.: 220991-20-8
• Molecular Formula: C15H13ClFNO2
• Molecular Weight: 293.725
• UNII: V91T9204HU
• DSSTox Substance ID: DTXSID9049035
• Nikkaji Number: J1.996.164H
• Wikipedia: Lumiracoxib
• Wikidata: Q413744
• NCI Thesaurus Code: C66041
• Pharos Ligand ID: A6BL9BHQCN9N
• Metabolomics Workbench ID: 43479
• ChEMBL ID: CHEMBL404108
• Mol file: 220991-20-8.mol

Synonyms:COX 189;COX-189;lumiracoxib;prexige

Chemical Property of Lumiracoxib

Chemical Property:

• Appearance/Colour: Pale yellow solid
• Vapor Pressure: 5.68E-07mmHg at 25°C
• Melting Point: 139-141 °C
• Refractive Index: 1.628
• Boiling Point: 395.7 °C at 760 mmHg
• PKA: 4.18±0.10(Predicted)
• Flash Point: 193.1 °C
• PSA: 49.33000
• Density: 1.363 g/cm³
• LogP: 4.23120
• Storage Temp.: -20°C Freezer
• Solubility.: ≥29.4 mg/mL in DMSO; insoluble in H2O; ≥27.15 mg/mL in EtOH with ultrasonic
• XLogP3: 4.2
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 4
• Exact Mass: 293.0618845
• Heavy Atom Count: 20
• Complexity: 342

Purity/Quality:

99% ^*data from raw suppliers

Lumiracoxib ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC1=CC(=C(C=C1)NC2=C(C=CC=C2Cl)F)CC(=O)O
• Recent ClinicalTrials: Efficacy of Lumiracoxib in Relieving Moderate to Severe Post-dental Surgery Pain, Compared to Both Placebo and Celecoxib
• Recent EU Clinical Trials: A retrospective pharmacogenetic analysis of patients with elevated liver enzymes (Hy s law cases or AST/ALT > 10x ULN) in clinical studies CCOX189A0117, CCOX189A2332, CCOX189A2369, CCOX189A0126, CCOX189A0112, CCOX189A0109 or CCOX189A2361
• Description: As a second-generation, selective cyclooxygenase (COX-2) inhibitor, lumiracoxib is devoid of the gastrointestinal issues that plague other non-selective, nonsteroidal, anti-inflammatory drugs (NSAIDs) that crossover to COX-1. As an inhibitor of the inducible COX-2 that is up-regulated in pathological processes of pain and inflammation, lumiracoxib blocks the conversion of arachidonic acid to prostaglandins, the mediators of the pathological effects. It’s mode of binding to COX-2 has been found to differ from the other selective COX-2 inhibitors; the carboxylic acid forms hydrogen bonds with Tyr-385 and Ser-530 in the catalytic site rather than seeking interactions within the larger hydrophobic side pocket. Since lumiracoxib is mainly metabolized by CYP2C9, a study evaluating the co-administration of lumiracoxib with fluconazole, a potent inhibitor of CYP2C9, was conducted, and it concluded that there was no need for lumiracoxib dose adjustment, since changes in the systemic exposure were not significant. No serious adverse effects were reported, but in the small number of cases where treatment was discontinued, Gastro intestinal (GI) and musculoskeletal complaints were common. Lumiracoxib is a selective inhibitor of COX-2 with IC50 values of 0.13 and 67 μM for COX-2 and COX-1, respectively, in isolated human whole blood. It reduces increases in the levels of prostaglandin E2 (PGE2; ) induced by IL-1β in human dermal fibroblasts (IC50 = 0.14 μM), as well as in LPS-stimulated RAW 264.7 cells when used at concentrations ranging from 1 to 100 μM., Lumiracoxib (3 and 10 mg/kg) also decreases LPS-induced increases in the levels of PGE2 in a rat model of air pouch inflammation. It reduces M. tuberculosis-induced increases in hind paw volume and the radiological and histopathological severity of arthritic lesions in a rat model of chronic arthritis when administered at a dose of 2 mg/kg.
• Uses: Lumiracoxib is a selective cyclooxygenase-2-(COX-2) inhibitor and an anti-inflammatory agent (1,2,3,4). Selective cyclooxygenase-2-(COX-2) inhibitor. Anti-inflammatory. antiinflammatory, analgesic, antiarthritic

Technology Process of Lumiracoxib

There total 23 articles about Lumiracoxib 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: 90.0%

1-(2-chloro-6-fluorophenyl)-5-methylindolin-2-one (332903-83-0) → lumiracoxib (220991-20-8)

Guidance literature:

With sodium hydroxide; In ethanol; water; Heating;

DOI:10.1016/j.tet.2004.09.064

Reference yield: 41.0%

potassium 2-iodo-5-methylphenylacetate (1234562-75-4) + 2-chloro-6-fluoroaniline (363-51-9) → lumiracoxib (220991-20-8)

Guidance literature:

With 1-methyl-pyrrolidin-2-one; copper(l) iodide; potassium carbonate; at 100 ℃;

DOI:10.1021/ol1010483

Reference yield:

2-chloro-6-fluoroaniline (363-51-9) → lumiracoxib (220991-20-8)

Guidance literature:

Multi-step reaction with 7 steps

1.1: NaH / dimethylformamide / 1 h / 0 - 4 °C

1.2: 91 percent / dimethylformamide / 20 h / 50 - 55 °C

2.1: HCl gas / ethyl acetate / 2.5 h / -5 - 0 °C

2.2: H₂O / ethyl acetate / 36 h / 20 - 25 °C

3.1: 80 percent / H₂SO₄; EtOH; H₂O / H₂O / 4 h / 66 - 70 °C

4.1: 83 percent / Red-Al / toluene / 1.5 h / 60 - 62 °C

5.1: 82 percent / toluene / 80 - 90 °C

6.1: 80 percent / AlCl₃ / 3 h / 170 °C

7.1: 90 percent / aq. NaOH / ethanol; H₂O / Heating

With hydrogenchloride; sodium hydroxide; aluminium trichloride; ethanol; sulfuric acid; water; sodium hydride; sodium bis(2-methoxyethoxy)aluminium dihydride; In ethanol; water; ethyl acetate; N,N-dimethyl-formamide; toluene; 6.1: Friedel-Crafts cyclization;

DOI:10.1016/j.tet.2004.09.064

upstream raw materials:

1-(2-chloro-6-fluorophenyl)-5-methylindolin-2-one

4-Cyanochlorobenzene

para-bromotoluene

2-chloro-6-fluorophenol

Downstream raw materials:

C₁₅H₁₄ClFN₂O₂

C₁₆H₁₃ClFN₃O₂

2-[(2-chloro-6-fluorophenyl)amino]-5-methylbenzeneacetic acid methyl ester

1-(2-chloro-6-fluorophenyl)-5-methylindolin-2-one

Refernces

• 1、 -. "CO-CRYSTALS OF TRAMADOL AND COXIBS". . . Retrieved 2012/07/14.
• 2、 -. "Process for phenylacetic acid derivatives". Page/Page column 21. . Retrieved 2008/12/04.