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Details

Stereochemistry ACHIRAL
Molecular Formula C17H12Br2O3
Molecular Weight 424.083
Optical Activity UNSPECIFIED
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of BENZBROMARONE

SMILES

CCC1=C(C(=O)C2=CC(Br)=C(O)C(Br)=C2)C3=C(O1)C=CC=C3

InChI

InChIKey=WHQCHUCQKNIQEC-UHFFFAOYSA-N
InChI=1S/C17H12Br2O3/c1-2-13-15(10-5-3-4-6-14(10)22-13)16(20)9-7-11(18)17(21)12(19)8-9/h3-8,21H,2H2,1H3

HIDE SMILES / InChI

Description

Benzbromarone (INN) is a uricosuric agent and non-competitive inhibitor of xanthine oxidase used in the treatment of gout, especially when the first line treatment, allopurinol, fails or produces intolerable adverse effects. It is structurally related to the antiarrhythmic amiodarone. Benzbromarone was introduced in the 1970s and was viewed as having few associated serious adverse reactions. It was registered in about 20 countries throughout Asia, South America and Europe. In 2003, the drug was withdrawn by Sanofi-Synthélabo, after reports of serious hepatotoxicity, although it is still marketed in several countries by other drug companies. The withdrawal has greatly limited its availability around the world and increased difficulty in accessing it in other countries where it has never been available. Standard dosages of benzbromarone (100 mg/day) tend to produce greater hypouricaemic effects than standard doses of allopourinol (300 mg/day) or probenecid (1000 mg/day). Adverse effects associated with benzbromarone are relatively infrequent but potentially severe. Four cases of benzbromarone-induced hepatotoxicity were identified from primary literature, and eleven cases have been reported by Sanofi-Synthélabo but details are not available in the public domain. Only one of the four publicly published cases demonstrated a clear relationship between the drug and liver injury as demonstrated by rechallenge. The other three cases lacked incontrovertible evidence to support a diagnosis of benzbromarone-induced hepatotoxicity. If all the reported cases are assumed to be due to benzbromarone, the estimated risk of hepatotoxicity in Europe was approximately 1 in 17 000 patients but may be higher in Japan. Benzbromarone is a very potent inhibitor of CYP2C9. The mechanism of benzbromarone hepatotoxicity is believed to be due to its hepatic metabolism by CYP2C9 and possible effects of the parent compound or its metabolites on mitochondrial function. Benzbromarone is a benzofuran and shares structural similarities with benzarone and amiodarone, all three of which affect mitochondrial function.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
EXURATE
PubMed

PubMed

TitleDatePubMed
Toxicological studies on a benzofurane derivative. I. A comparative study with phenobarbital on rat liver.
1990 Dec
Charge and substituent effects on affinity and metabolism of benzbromarone-based CYP2C19 inhibitors.
2004 Dec 30
Gout in solid organ transplantation: a challenging clinical problem.
2005
Sulfasalazine transport in in-vitro, ex-vivo and in-vivo absorption models: contribution of efflux carriers and their modulation by co-administration of synthetic nature-identical fruit extracts.
2005 Dec
Phenothiazine maleates stimulate MRP1 transport activity in human erythrocytes.
2005 Dec 30
Optimal management of chronic gout: attempting to render the (t)issues crystal-clear.
2005 Jun 24
Benzbromarone therapy in management of refractory gout.
2005 Jun 24
Prediction of CYP2C9-mediated drug-drug interactions: a comparison using data from recombinant enzymes and human hepatocytes.
2005 Nov
[Clinical observation on electroacupuncture combined with medicine for treatment of acute gouty arthritis].
2005 Oct
Uric acid causes vascular smooth muscle cell proliferation by entering cells via a functional urate transporter.
2005 Sep-Oct
Inhibition of MRP1-mediated efflux in human erythrocytes by mono-anionic bile salts.
2005 Sep-Oct
Recent developments in our understanding of the renal basis of hyperuricemia and the development of novel antihyperuricemic therapeutics.
2006
A concise history of gout and hyperuricemia and their treatment.
2006
Ciprofloxacin permeability and its active secretion through rat small intestine in vitro.
2006 Apr 26
Profiling of gene expression in rat liver and rat primary cultured hepatocytes treated with peroxisome proliferators.
2006 Dec
Utilization of a one-dimensional score for surveying chemical-induced changes in expression levels of multiple biomarker gene sets using a large-scale toxicogenomics database.
2006 Dec
[Molecular mechanism in biological transport in the kidney: Urate transporter URAT1].
2006 Feb
The evaluation of some pharmaceutically acceptable excipients as permeation enhancers for amoxicillin.
2006 Feb 3
Effect of fenofibrate in combination with urate lowering agents in patients with gout.
2006 Jun
A convergent synthetic study of biologically active benzofuran derivatives.
2006 Jun
Micellar electrokinetic capillary chromatographic method for the quantitative analysis of uricosuric and antigout drugs in pharmaceutical preparations.
2006 Jun
A causal role for uric acid in fructose-induced metabolic syndrome.
2006 Mar
Antihyperuricemic lignans from the leaves of Phyllanthus niruri.
2006 Nov
[The inhibition of CYP2C9 isoenzyme in Cunninghamella blakesleeana AS 3. 910].
2006 Oct
Amiodarone analog-dependent effects on CYP2C9-mediated metabolism and kinetic profiles.
2006 Oct
EULAR evidence based recommendations for gout. Part II: Management. Report of a task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT).
2006 Oct
Using serum urate levels to determine the period free of gouty symptoms after withdrawal of long-term urate-lowering therapy: a prospective study.
2006 Oct 15
Activating effect of benzbromarone, a uricosuric drug, on peroxisome proliferator-activated receptors.
2007
Emerging therapies in the long-term management of hyperuricaemia and gout.
2007 Apr
Block of CFTR-dependent chloride currents by inhibitors of multidrug resistance-associated proteins.
2007 Apr 10
Sequential metabolism and bioactivation of the hepatotoxin benzbromarone: formation of glutathione adducts from a catechol intermediate.
2007 Dec
Morin (3,5,7,2',4'-pentahydroxyflavone) exhibits potent inhibitory actions on urate transport by the human urate anion transporter (hURAT1) expressed in human embryonic kidney cells.
2007 Jun
Correctors promote maturation of cystic fibrosis transmembrane conductance regulator (CFTR)-processing mutants by binding to the protein.
2007 Nov 16
Gene expression profiling of rat liver treated with serum triglyceride-decreasing compounds.
2007 Oct
Biochemical effectiveness of allopurinol and allopurinol-probenecid in previously benzbromarone-treated gout patients.
2007 Sep
Excellent response to the clinical treatment of tophaceous gout.
2007 Sep
Flow cytometric monitoring of multidrug drug resistance protein 1 (MRP1/ABCC1) -mediated transport of 2',7'-bis-(3-carboxypropyl)-5-(and-6)- carboxyfluorescein (BCPCF) into human erythrocyte membrane inside-out vesicles.
2007 Sep-Dec
A benefit-risk assessment of benzbromarone in the treatment of gout. Was its withdrawal from the market in the best interest of patients?
2008
[Usefulness of combination treatment using allopurinol and benzbromarone for gout and hyperuricemia accompanying renal dysfunction: kinetic analysis of oxypurinol].
2008
[New antihyperuricemic medicine: febuxostat, Puricase, etc].
2008 Apr
[Uricosuric agent].
2008 Apr
[Establishment of therapeutic goal and plan of gout and asymptomatic hyperuricemia].
2008 Apr
Modeling and synthesis of novel tight-binding inhibitors of cytochrome P450 2C9.
2008 Apr 1
Effect of hypouricaemic and hyperuricaemic drugs on the renal urate efflux transporter, multidrug resistance protein 4.
2008 Dec
Gout in the UK and Germany: prevalence, comorbidities and management in general practice 2000-2005.
2008 Jul
[Stage-based treatment of gouty arthritis by combination therapy of traditional Chinese and Western medicines: a randomized controlled trial].
2008 Jun
Modulation of sinusoidal and canalicular elimination of bilirubin-glucuronides by rifampicin and other cholestatic drugs in a sandwich culture of rat hepatocytes.
2008 Mar
Uricosuric action of losartan via the inhibition of urate transporter 1 (URAT 1) in hypertensive patients.
2008 Oct
Efficacy and tolerability of urate-lowering drugs in gout: a randomised controlled trial of benzbromarone versus probenecid after failure of allopurinol.
2009 Jan
A randomised controlled trial on the efficacy and tolerability with dose escalation of allopurinol 300-600 mg/day versus benzbromarone 100-200 mg/day in patients with gout.
2009 Jun
Patents

Patents

Sample Use Guides

In Vivo Use Guide
The usual dose: 100mg per day 50 – 200 mg per day may be used
Route of Administration: Oral
In Vitro Use Guide
Microsomes from human livers were preincubated with benzbromarone and NADPH, followed by evaluation of CYP2C9 and CYP3A4 activities.
Name Type Language
BENZBROMARONE
EP   INN   MART.   MI   USAN   WHO-DD  
USAN   INN  
Official Name English
MJ-10061
Code English
BENZBROMARONE [USAN]
Common Name English
3,5-DIBROMO-4-HYDROXYPHENYL-2-ETHYL-3-BENZOFURANYL KETONE
Systematic Name English
BENZBROMARON
Common Name English
BENZBROMARONE [INN]
Common Name English
BENZPROMARONE
Common Name English
MJ 10061
Code English
L-2214
Code English
BENZBROMARONE [MI]
Common Name English
BENZBROMARONE [JAN]
Common Name English
METHANONE, (3,5-DIBROMO-4-HYDROXYPHENYL)(2-ETHYL-3-BENZOFURANYL)-
Systematic Name English
BENZBROMARONE [EP]
Common Name English
UROLEAP
Brand Name English
BENZBROMARONE [WHO-DD]
Common Name English
NSC-85433
Code English
BENZBROMARONE [MART.]
Common Name English
Classification Tree Code System Code
WHO-ATC M04AB03
Created by admin on Tue Oct 22 06:11:32 UTC 2019 , Edited by admin on Tue Oct 22 06:11:32 UTC 2019
WHO-VATC QM04AB03
Created by admin on Tue Oct 22 06:11:32 UTC 2019 , Edited by admin on Tue Oct 22 06:11:32 UTC 2019
LIVERTOX 96
Created by admin on Tue Oct 22 06:11:32 UTC 2019 , Edited by admin on Tue Oct 22 06:11:32 UTC 2019
NCI_THESAURUS C921
Created by admin on Tue Oct 22 06:11:32 UTC 2019 , Edited by admin on Tue Oct 22 06:11:32 UTC 2019
Code System Code Type Description
WIKIPEDIA
BENZBROMARONE
Created by admin on Tue Oct 22 06:11:32 UTC 2019 , Edited by admin on Tue Oct 22 06:11:32 UTC 2019
PRIMARY
EPA CompTox
3562-84-3
Created by admin on Tue Oct 22 06:11:32 UTC 2019 , Edited by admin on Tue Oct 22 06:11:32 UTC 2019
PRIMARY
ChEMBL
CHEMBL388590
Created by admin on Tue Oct 22 06:11:32 UTC 2019 , Edited by admin on Tue Oct 22 06:11:32 UTC 2019
PRIMARY
ECHA (EC/EINECS)
222-630-7
Created by admin on Tue Oct 22 06:11:32 UTC 2019 , Edited by admin on Tue Oct 22 06:11:32 UTC 2019
PRIMARY
CAS
3562-84-3
Created by admin on Tue Oct 22 06:11:32 UTC 2019 , Edited by admin on Tue Oct 22 06:11:32 UTC 2019
PRIMARY
MERCK INDEX
M2337
Created by admin on Tue Oct 22 06:11:32 UTC 2019 , Edited by admin on Tue Oct 22 06:11:32 UTC 2019
PRIMARY Merck Index
PUBCHEM
2333
Created by admin on Tue Oct 22 06:11:32 UTC 2019 , Edited by admin on Tue Oct 22 06:11:32 UTC 2019
PRIMARY
EVMPD
SUB05743MIG
Created by admin on Tue Oct 22 06:11:32 UTC 2019 , Edited by admin on Tue Oct 22 06:11:32 UTC 2019
PRIMARY
RXCUI
1385
Created by admin on Tue Oct 22 06:11:32 UTC 2019 , Edited by admin on Tue Oct 22 06:11:32 UTC 2019
PRIMARY RxNorm
NCI_THESAURUS
C74412
Created by admin on Tue Oct 22 06:11:32 UTC 2019 , Edited by admin on Tue Oct 22 06:11:32 UTC 2019
PRIMARY
INN
1427
Created by admin on Tue Oct 22 06:11:32 UTC 2019 , Edited by admin on Tue Oct 22 06:11:32 UTC 2019
PRIMARY
MESH
D001553
Created by admin on Tue Oct 22 06:11:32 UTC 2019 , Edited by admin on Tue Oct 22 06:11:32 UTC 2019
PRIMARY