FEBUXOSTAT

Details

Stereochemistry	ACHIRAL
Molecular Formula	C16H16N2O3S
Molecular Weight	316.375
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)COC1=C(C=C(C=C1)C2=NC(C)=C(S2)C(O)=O)C#N

InChI

InChIKey=BQSJTQLCZDPROO-UHFFFAOYSA-N

InChI=1S/C16H16N2O3S/c1-9(2)8-21-13-5-4-11(6-12(13)7-17)15-18-10(3)14(22-15)16(19)20/h4-6,9H,8H2,1-3H3,(H,19,20)

HIDE SMILES / InChI

Molecular Formula	C16H16N2O3S
Molecular Weight	316.375
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description

Febuxostat (ULORIC) is a novel, xanthine oxidase/dehydrogenase (XO/XDH) inhibitor being developed by Teijin, TAP Pharmaceuticals, and Ipsen for the treatment of gout. The currently available XO inhibitor, allopurinol, has been associated with serious instances of severe hypersensitivity, in some cases leading to fatalities. There is some suggestion that febuxostat is less prone to excacerbate systemic inflammatory events in animal studies. Febuxostat, a xanthine oxidase inhibitor, achieves its therapeutic effect by decreasing serum uric acid. Febuxostat is not expected to inhibit other enzymes involved in purine and pyrimidine synthesis and metabolism at therapeutic concentrations. Febuxostat is used for the treatment of hyperuricemia in patients with gout.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Xanthine dehydrogenase 27	Inhibitor 7468	Hyperuricemia	1.26 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hyperuricemia 6	Primary	Xanthine dehydrogenase	Approved 7883	Uloric
Kidney stones (in people with high uric acid levels) 1			Approved (off-label) 8

PubMed

Title	Date	PubMed
Gateways to clinical trials.	2007 Dec	18200333
Febuxostat: a novel non-purine selective inhibitor of xanthine oxidase for the treatment of hyperuricemia in gout.	2007 Feb	19075968
Developments in the scientific and clinical understanding of gout.	2008	18947374
Febuxostat : a viewpoint by N. Lawrence Edwards.	2008	18729540
Febuxostat : a viewpoint by Naomi Schlesinger.	2008	18729539
Febuxostat: a viewpoint by H. Ralph Schumacher Jr and Lan X. Chen.	2008	18729538
Febuxostat.	2008	18729537
A benefit-risk assessment of benzbromarone in the treatment of gout. Was its withdrawal from the market in the best interest of patients?	2008	18636784
Effect of febuxostat on the progression of renal disease in 5/6 nephrectomy rats with and without hyperuricemia.	2008	18434753
Gateways to clinical trials.	2008 Apr	18597009
[New antihyperuricemic medicine: febuxostat, Puricase, etc].	2008 Apr	18409528
[Inhibitors of xanthine oxidoreductase].	2008 Apr	18409526
Effects of febuxostat on metabolic and renal alterations in rats with fructose-induced metabolic syndrome.	2008 Apr	18216151
Treatment with the xanthine oxidase inhibitor febuxostat lowers uric acid and alleviates systemic and glomerular hypertension in experimental hyperuricaemia.	2008 Apr	18048425
Febuxostat in the management of hyperuricemia and chronic gout: a review.	2008 Dec	19337428
Crystal structures of mammalian xanthine oxidoreductase bound with various inhibitors: allopurinol, febuxostat, and FYX-051.	2008 Feb	18360072
Chronic xanthine oxidase inhibition following myocardial infarction in rabbits: effects of early versus delayed treatment.	2008 Feb 27	18215719
Determinants of the clinical outcomes of gout during the first year of urate-lowering therapy.	2008 Jun	18600509
Refractory gout: what is it and what to do about it?	2008 Mar	18349751
Effect of food or antacid on pharmacokinetics and pharmacodynamics of febuxostat in healthy subjects.	2008 Mar	17953718
In vitro drug-drug interaction studies with febuxostat, a novel non-purine selective inhibitor of xanthine oxidase: plasma protein binding, identification of metabolic enzymes and cytochrome P450 inhibition.	2008 May	18421623
Xanthine oxidase inhibition with febuxostat attenuates systolic overload-induced left ventricular hypertrophy and dysfunction in mice.	2008 Nov	18995179
Effects of febuxostat versus allopurinol and placebo in reducing serum urate in subjects with hyperuricemia and gout: a 28-week, phase III, randomized, double-blind, parallel-group trial.	2008 Nov 15	18975369
Gout management: let's get it right this time.	2008 Nov 15	18975368
Gateways to clinical trials.	2008 Oct	19088949
The effect of age and gender on pharmacokinetics, pharmacodynamics, and safety of febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase.	2008 Sep	18635756
The role of urate and xanthine oxidase in vascular oxidative stress: future directions.	2009	19851527
Gout. Hyperuricemia and cardiovascular disease: how strong is the evidence for a causal link?	2009	19725932
Gout. Novel therapies for treatment of gout and hyperuricemia.	2009	19664185
Role of urate, xanthine oxidase and the effects of allopurinol in vascular oxidative stress.	2009	19436671
Febuxostat: new drug. Hyperuricaemia: risk of gout attacks.	2009 Apr	19585722
Gateways to clinical trials.	2009 Apr	19536362
Febuxostat: a new agent for lowering serum urate.	2009 Apr	19499090
A critical reappraisal of allopurinol dosing, safety, and efficacy for hyperuricemia in gout.	2009 Apr	19296886
New gout treatment approved.	2009 Apr 1	19299362
Nickel-catalyzed biaryl coupling of heteroarenes and aryl halides/triflates.	2009 Apr 16	19296639
Febuxostat in the treatment of gout: 5-yr findings of the FOCUS efficacy and safety study.	2009 Feb	19141576
Gout Study Group: update on hyperuricemia and gout.	2009 Jul	19559637
Gout--what are the treatment options?	2009 Jun	19463070
Clinical efficacy and safety of successful longterm urate lowering with febuxostat or allopurinol in subjects with gout.	2009 Jun	19286847
Update on emerging urate-lowering therapies.	2009 Mar	19339925
Febuxostat.	2009 Mar	19247302
Febuxostat: a new treatment for hyperuricaemia in gout.	2009 May	19447778
Febuxostat (Uloric) for chronic treatment of gout.	2009 May 18	19448587
New drugs: Febuxostat, lacosamide, and rufinamide.	2009 May-Jun	19443330
Approach to the treatment of hyperuricemia.	2009 Nov	19999894
[Crystal-induced activation of the inflammasome: gout and pseudogout].	2009 Nov	19838718
Febuxostat for the treatment of hyperuricaemia in people with gout: a single technology appraisal.	2009 Oct	19846027
Update on gout and hyperuricemia.	2010 Feb	19909378
Update on gout: new therapeutic strategies and options.	2010 Jan	20046204

Patents

Sample Use Guides

In Vivo Use Guide

For treatment of hyperuricemia in patients with gout, the recommended dose is 40 mg or 80 mg once daily.

Route of Administration: Oral

In Vitro Use Guide

Febuxostat (200uM) inhibited cholesterol crystal-induced ROS formation and inflammatory cytokine release in murine macrophages.

Substance Class	Chemical Created by `admin` on `Mon Oct 21 20:28:10 UTC 2019` Edited by `admin` on `Mon Oct 21 20:28:10 UTC 2019`
Record UNII	101V0R1N2E
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

FEBUXOSTAT

Official Name

English

FEBUXOSTAT [VANDF]

Common Name

English

TMX-67

Code

English

2-(3-CYANO-4-ISOBUTOXYPHENYL)-4-METHYL-1,3-THIAZOLE-5-CARBOXYLIC ACID

Systematic Name

English

FEBUXOSTAT [USAN]

Common Name

English

FEBUXOSTAT [MI]

Common Name

English

FEBUXOSTAT [INN]

Common Name

English

ADENURIC

Brand Name

English

5-THIAZOLECARBOXYLIC ACID, 2-(3-CYANO-4-(2-METHYLPROPOXY)PHENYL)-4-METHYL-

Systematic Name

English

FEBUXOSTAT [JAN]

Common Name

English

FEBUXOSTAT [EMA EPAR]

Common Name

English

FEBUXOSTAT [MART.]

Common Name

English

FEBUXOSTAT [WHO-DD]

Common Name

English

ULORIC

Brand Name

English

FEBUXOSTAT [ORANGE BOOK]

Common Name

English

Classification Tree Code System Code

LIVERTOX

400