2-{2-[(2-chloro-6-fluorophenyl)amino]-5-methylphenyl}acetic acid

• ChemBase ID: 1141
• Molecular Formular: C15H13ClFNO2
• Molecular Mass: 293.7206232
• Monoisotopic Mass: 293.06188456
• SMILES: Clc1c(Nc2c(cc(cc2)C)CC(=O)O)c(F)ccc1
• Canonical SMILES: OC(=O)Cc1cc(C)ccc1Nc1c(F)cccc1Cl
• InChI: InChI=1S/C15H13ClFNO2/c1-9-5-6-13(10(7-9)8-14(19)20)18-15-11(16)3-2-4-12(15)17/h2-7,18H,8H2,1H3,(H,19,20)
• InChIKey: KHPKQFYUPIUARC-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 2-{2-[(2-chloro-6-fluorophenyl)amino]-5-methylphenyl}acetic acid
• IUPAC Traditional name: lumiracoxib
• Brand Name: Prexige (Novartis); Prexige
• Synonyms: lumiracoxib; COX 189; Lumiracoxib; 2-[(2-Chloro-6-fluorophenyl)amino]-5-methylbenzeneacetic Acid; 2-[2-(2-Chloro-6-fluorophenylamino)-5-methylphenyl]acetic Acid; CGS 35189; Prexige; Lumiracoxib (COX-189)

Database IDs

• CAS Number: 220991-20-8
• PubChem SID: 160964604; 46506378
• PubChem CID: 151166

CALCULATED PROPERTIES

JChem

• Acid pKa: 4.114901
• H Acceptors: 3
• H Donor: 2
• LogD (pH = 5.5): 2.911556
• LogD (pH = 7.4): 1.2215736
• Log P: 4.311088
• Molar Refractivity: 75.9142 cm^3
• Polarizability: 28.60001 Å^3
• Polar Surface Area: 49.33 Å^2
• Rotatable Bonds: 4
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 4.56
• LOG S: -4.73
• Solubility (Water): 5.49e-03 g/l

PROPERTIES

Physical Property

• Solubility: DMSO
• Apperance: Pale Yellow Solid
• Melting Point: 139-141°C
• Hydrophobicity(logP): 3.9

Safety Information

• Storage Condition: -20°C Freezer

Pharmacology Properties

• Target: COX

Product Information

• Salt Data: Free Base

DETAILS

DrugBank - DB01283

• Drug Groups: approved; investigational
• Description: Lumiracoxib is a COX-2 selective inhibitor non-steroidal anti-inflammatory drug. On August 11, 2007, Australia's Therapeutic Goods Administration (TGA, the Australian equivalent of the FDA) cancelled the registration of lumiracoxib in Australia due to concerns that it may cause liver failure. New Zealand and Canada have also followed suit in recalling the drug.
• Indication: For the acute and chronic treatment of the signs and symptoms of osteoarthritis of the knee in adults.
• Pharmacology: Lumiracoxib has a different structure from the standard COX-2 inhibitors (e.g. celecoxib). It more closely resembles the structure of diclofenac (one chlorine substituted by fluorine, the phenylacetic acid has another methyl group in meta position), making it a member of the arylalkanoic acid family of NSAIDs. It binds to a different site on the COX-2 receptor than the standard COX-2 inhibitors. It displays extremely high COX-2 selectivity.
• Toxicity: Single oral doses in mice and rats resulted in mortality and/or moribundity at doses of 600 mg/kg and 500 mg/kg, respectively. Single intraperitoneal doses in mice and rats results in mortality/moribundity at 750 mg/kg and 1000 mg/kg, respectively. The maximum non-lethal single oral and intraperitoneal dose in mouse was 300 mg/kg and 250 mg/kg, respectively. In the rat it was 150 mg/kg and 250 mg/kg, respectively.
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic oxidation and hydroxylation via CYP2C9. Three major metabolites have been identified in plasma: 4'-hydroxy-lumiracoxib, 5-carboxy-lumiracoxib, and 4'-hydroxy-5-carboxy-lumiracoxib.
• Absorption: Rapidly absorbed following oral administration, with an absolute oral bioavailablity of 74%.
• Half Life: Terminal half-life is approximately 4 hours.
• Protein Binding: Highly bound to plasma proteins (>= 98%).
• External Links: Wikipedia

Toronto Research Chemicals - L474700

Selective cyclooxygenase-2-(COX-2) inhibitor. Anti-inflammatory.

REFERENCES

• Bitner, M., et al.: Int. J. Clin. Pract., 58, 340 (2004)
• Packman, E., et al.: Headache, 45, 1163 (2004)
• Rordorf, C.M., et al.: Clin. Pharmacokinet., 44. 1247 (2004)
• Schnitzer, T.J., et al.: Curr. Med. Res. Opin., 21, 151 (2004)