Febuxostat

Base Information

• Chemical Name: Febuxostat
• CAS No.: 144060-53-7
• Molecular Formula: C₁₆H₁₆N₂O₃S
• Molecular Weight: 316.381
• Hs Code.: 2934100090
• European Community (EC) Number: 682-158-6
• NSC Number: 758874
• UNII: 101V0R1N2E
• DSSTox Substance ID: DTXSID8048650
• Nikkaji Number: J551.973J
• Wikipedia: Febuxostat
• Wikidata: Q417296
• NCI Thesaurus Code: C65629
• RXCUI: 73689
• Pharos Ligand ID: QXZ97DF5M3KC
• Metabolomics Workbench ID: 149284
• ChEMBL ID: CHEMBL1164729
• Mol file: 144060-53-7.mol

Synonyms:2-(3-cyano-4-isobutoxyphenyl)-4-methyl-5-thiazolecarboxylic acid;6720, TEI;febuxostat;TEI 6720;TEI-6720;TEI6720;uloric

Chemical Property of Febuxostat

Chemical Property:

• Appearance/Colour: crystalline solid
• Vapor Pressure: 2.41E-12mmHg at 25°C
• Melting Point: 238-239 °C
• Refractive Index: 1.605
• Boiling Point: 536.6 °C at 760 mmHg
• PKA: 2.48±0.10(Predicted)
• Flash Point: 278.3 °C
• PSA: 111.45000
• Density: 1.31 g/cm³
• LogP: 3.72318
• Storage Temp.: Refrigerator
• Solubility.: DMSO (Slightly), Methanol (Slightly)
• XLogP3: 3.9
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 5
• Exact Mass: 316.08816355
• Heavy Atom Count: 22
• Complexity: 448

Purity/Quality:

99% ^*data from raw suppliers

Febuxostat ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antigout Agents/Gout Suppressants
• Canonical SMILES: CC1=C(SC(=N1)C2=CC(=C(C=C2)OCC(C)C)C#N)C(=O)O
• Recent ClinicalTrials: A Therapeutic Confirmatory Study of Epaminurad Versus Febuxostat in Gout Patients
• Recent EU Clinical Trials: The Gout TrEatment STrategy Project (GO TEST) Overture trial
• Recent NIPH Clinical Trials: PK & PD of coadministration of XOR inhibitor and inosine
• Mechanism of Action: Febuxostat is a xanthine oxidase inhibitor that decreases uric acid production in the body.
• Approval and Dosages: Approved by regulatory authorities such as the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) for managing gout.; Dosages approved by EMA: 80 and 120 mg/day.; Dosages approved by FDA: 40 and 80 mg/day, based on an additional review of the CONFIRMS trial.
• Safety and Efficacy: Febuxostat demonstrated better safety outcomes compared to allopurinol, showing a reduction in urgent coronary revascularization and stroke.; Non-inferior to allopurinol therapy in terms of primary cardiovascular endpoint, with no increased risk of death or serious adverse events associated with long-term use.
• Comparative Efficacy and Safety: Febuxostat, a non-purine selective inhibitor of xanthine oxidase, is more effective than allopurinol in lowering uric acid levels in patients with hyperuricemia and gout.; Regulatory trials compared fixed doses of febuxostat against a maximum fixed dose of 300 mg of allopurinol, rather than employing a titrate-to-target approach as recommended by guidelines.; Febuxostat's labeling provides guidance on use in chronic kidney disease patients, whereas allopurinol's labeling does not.; FDA issued a boxed warning regarding febuxostat's cardiovascular safety based on the Cardiovascular Safety of Febuxostat and Allopurinol in Patients with Gout (CARES) trial results.

Technology Process of Febuxostat

There total 70 articles about Febuxostat 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: 100.0%

tert-butyl 2-(3’-cyano-4’-isobutoxyphenyl)-4-methylthiazole-5-carboxylate (1139901-88-4) → febuxostat (144060-53-7)

Guidance literature:

With trifluoroacetic acid; In dichloromethane; at 20 ℃; for 5h;

DOI:10.1021/ol9001587

Reference yield: 98.71%

Isobutyl bromide (78-77-3) + ethyl 2‐(3‐formyl‐4‐hydroxyphenyl)‐4‐methylthiazole‐5‐carboxylate (161798-01-2) → febuxostat (144060-53-7)

Guidance literature:

With potassium carbonate; N,N-dimethyl-formamide; In toluene; at 105 ℃; for 4h;

Reference yield: 98.0%

2-(3-cyano-4-isobutyloxyphenyl)-4-methylthiazole-5-carboxylic acid ethyl ester (160844-75-7) → febuxostat (144060-53-7)

Guidance literature:

With water; sodium hydroxide; In tetrahydrofuran; ethanol; at 40 ℃; for 5h;

DOI:10.1021/acs.oprd.8b00164

upstream raw materials:

2-(3-cyano-4-isobutyloxyphenyl)-4-methylthiazole-5-carboxylic acid ethyl ester

4-isobutoxyisophthalonitrile

3-cyanoisobutoxybenzothioamide

4-nitrobenzonitrile

Refernces

• 1、 Sam Daniel Prabu,Lakshmanan, Sivalingam,Thirumurugan,Ramalakshmi,Arul Antony. "Synthesis, molecular docking, DFT study of novel N-benzyl-2-(3-cyano-4-isobutoxyphenyl)-4-methylthiazole-5-carboxamide derivatives and their antibacterial activity". . p. 619 - 626. Retrieved 2020.
• 2、 -. "New preparation method of febuxostat intermediate". Paragraph 0129-0131. . Retrieved 2020/03/06.