Saturday, 13 December 2014

FEBUXOSTAT........WO2011141933 PATENT REVIEW

Febuxostat

Febuxostat

Febuxostat
Febuxostat.svg
Systematic (IUPAC) name
2-(3-cyano-4-isobutoxyphenyl)-4-methyl-
1,3-thiazole-5-carboxylic acid
Clinical data
Trade namesUloric, Adenuric, Atenurix
AHFS/Drugs.commonograph
MedlinePlusa609020
Licence dataEMA:LinkUS FDA:link
Pregnancy cat.
Legal status
RoutesOral
Pharmacokinetic data
Bioavailability~49% absorbed
Protein binding~99% to albumin
Metabolismvia CYP1A22C82C9,UGT1A11A31A92B7
Half-life~5-8 hours
ExcretionUrine (~49% mostly as metabolites, 3% as unchanged drug); feces (~45% mostly as metabolites, 12% as unchanged drug)
Identifiers
CAS number144060-53-7 
ATC codeM04AA03
PubChemCID 134018
ChemSpider118173 Yes
UNII101V0R1N2E Yes
KEGGD01206 Yes
ChEMBLCHEMBL1164729 Yes
Chemical data
FormulaC16H16N2O3S 
Mol. mass316.374 g/mol


MORE................
Febuxostat is an inhibitor of xanthine oxidase, and was developed by Teijin pharma. This compound is known as a new drug that is effective against gout and hyperuricemia, and it has been 40 years since the last time a drug of this kind of drug was developed.
Febuxostat has therefore gained a lot of popularity and it has already been accepted as a drug in Europe, USA, Korea and Japan. The synthesis of this molecule have been reported in patents by Teijin pharma as shown below.[1,2]

2014-04-20_05-03-25
Recently, Itami group was reported the rapoid synthesis of febxostat by using Ni-catalyzed direct coupling of azoles and arylhalides[3]
  • References

Sorbera, L.A.; Castaner, J.; Rabasseda, X.; Revel, L.; TMX-67. Drugs Fut 2001, 26, 1, 32
[1] Hasegawa, M.; A facile one-pot synthesis of 4-alkoxy-1,3-benzenedicarbonitrile. Heterocycles 1998, 47, 2, 857. [2] Hasegawa, M.;  Hasegawa, M.; Komoriya, K. (Teijin Ltd.); Cyano cpds. and their preparation method. JP 1994345724 . [3] “Nickel-Catalyzed Biaryl Coupling of Heteroarenes and Aryl Halides/Triflates”
Canivet, J.; Yamaguchi, J.; Ban, I.; Itami, K. Org. Lett. 200911, 1733-1736. DOI: 10.1021/ol9001587
ol-2009-001587_0001
Ni-based catalytic systems for the arylation of heteroarenes with aryl halides and triflates have been established. Ni(OAc)2/bipy is a general catalyst for aryl bromides/iodides, and Ni(OAc)2/dppf is effective for aryl chlorides/triflates. Thiazole, benzothiazole, oxazole, benzoxazole, and benzimidazole are applicable as heteroarene coupling partners. A rapid synthesis of febuxostat, a drug for gout and hyperuricemia, is also demonstrated.
SEE,,,,,,,,http://www.allfordrugs.com/2016/07/10/febuxostat/

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