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Details

Stereochemistry ACHIRAL
Molecular Formula C17H12Br2O3
Molecular Weight 424.0831
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of BENZBROMARONE

SMILES

CCc1c(c2ccccc2o1)C(=O)c3cc(c(c(c3)Br)O)Br

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
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 In 2003, the drug was withdrawn by Sanofi-Synthélabo, after reports of serious hepatotoxicity, although it is still marketed in several countries by other drug companies.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
Curative
EXURATE

Approved Use

For the chronic management of hyperuricemia in patients with gout.
PubMed

PubMed

TitleDatePubMed
Potentiation of anticoagulant effect of warfarin caused by enantioselective metabolic inhibition by the uricosuric agent benzbromarone.
1999 Dec
[Vesical uric acid lithiasis in a child with renal hypouricemia].
2001 Sep
Fulminant hepatic failure associated with benzbromarone treatment: a case report.
2002 May
Flavonoids as inhibitors of MRP1-like efflux activity in human erythrocytes. A structure-activity relationship study.
2003
[Drug therapy for idiopathic hyperuricemia--introduction, dose, and side effects].
2003 Jan
A new class of CYP2C9 inhibitors: probing 2C9 specificity with high-affinity benzbromarone derivatives.
2003 Jul
Effects of aspirin and/or salicylate on hydrolysis and glucuronidation of indomethacin in rat erythrocytes and hepatocytes.
2003 May
[Chronic gout. Case report of a severe course of disease].
2003 Nov 15
Management of acute and chronic gouty arthritis: present state-of-the-art.
2004
Clinical and molecular analysis of patients with renal hypouricemia in Japan-influence of URAT1 gene on urinary urate excretion.
2004 Jan
Spinal tophaceous gout mimicking a spinal tumor.
2004 Jul
Differential multidrug resistance-associated protein 1 through 6 isoform expression and function in human intestinal epithelial Caco-2 cells.
2004 Nov
Gout in solid organ transplantation: a challenging clinical problem.
2005
Mechanisms of benzarone and benzbromarone-induced hepatic toxicity.
2005 Apr
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
Involvement of uric acid transporter in increased renal clearance of the xanthine oxidase inhibitor oxypurinol induced by a uricosuric agent, benzbromarone.
2005 Dec
Phenothiazine maleates stimulate MRP1 transport activity in human erythrocytes.
2005 Dec 30
Inhibition of MRP1-mediated efflux in human erythrocytes by mono-anionic bile salts.
2005 Sep-Oct
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
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
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
Pseudotumor of gout in the patella of a kidney transplant recipient.
2007 Jun
Correctors promote maturation of cystic fibrosis transmembrane conductance regulator (CFTR)-processing mutants by binding to the protein.
2007 Nov 16
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
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
Modulation of sinusoidal and canalicular elimination of bilirubin-glucuronides by rifampicin and other cholestatic drugs in a sandwich culture of rat hepatocytes.
2008 Mar
Efficacy and tolerability of urate-lowering drugs in gout: a randomised controlled trial of benzbromarone versus probenecid after failure of allopurinol.
2009 Jan
Patents

Patents

Sample Use Guides

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 [EP MONOGRAPH]
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
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 Fri Jun 25 21:17:15 UTC 2021 , Edited by admin on Fri Jun 25 21:17:15 UTC 2021
WHO-VATC QM04AB03
Created by admin on Fri Jun 25 21:17:15 UTC 2021 , Edited by admin on Fri Jun 25 21:17:15 UTC 2021
LIVERTOX 96
Created by admin on Fri Jun 25 21:17:15 UTC 2021 , Edited by admin on Fri Jun 25 21:17:15 UTC 2021
NCI_THESAURUS C921
Created by admin on Fri Jun 25 21:17:15 UTC 2021 , Edited by admin on Fri Jun 25 21:17:15 UTC 2021
Code System Code Type Description
WIKIPEDIA
BENZBROMARONE
Created by admin on Fri Jun 25 21:17:15 UTC 2021 , Edited by admin on Fri Jun 25 21:17:15 UTC 2021
PRIMARY
DRUG BANK
DB12319
Created by admin on Fri Jun 25 21:17:15 UTC 2021 , Edited by admin on Fri Jun 25 21:17:15 UTC 2021
PRIMARY
DRUG CENTRAL
318
Created by admin on Fri Jun 25 21:17:15 UTC 2021 , Edited by admin on Fri Jun 25 21:17:15 UTC 2021
PRIMARY
EPA CompTox
3562-84-3
Created by admin on Fri Jun 25 21:17:15 UTC 2021 , Edited by admin on Fri Jun 25 21:17:15 UTC 2021
PRIMARY
ChEMBL
CHEMBL388590
Created by admin on Fri Jun 25 21:17:15 UTC 2021 , Edited by admin on Fri Jun 25 21:17:15 UTC 2021
PRIMARY
ECHA (EC/EINECS)
222-630-7
Created by admin on Fri Jun 25 21:17:15 UTC 2021 , Edited by admin on Fri Jun 25 21:17:15 UTC 2021
PRIMARY
CAS
3562-84-3
Created by admin on Fri Jun 25 21:17:15 UTC 2021 , Edited by admin on Fri Jun 25 21:17:15 UTC 2021
PRIMARY
MERCK INDEX
M2337
Created by admin on Fri Jun 25 21:17:15 UTC 2021 , Edited by admin on Fri Jun 25 21:17:15 UTC 2021
PRIMARY Merck Index
FDA UNII
4POG0RL69O
Created by admin on Fri Jun 25 21:17:15 UTC 2021 , Edited by admin on Fri Jun 25 21:17:15 UTC 2021
PRIMARY
PUBCHEM
2333
Created by admin on Fri Jun 25 21:17:15 UTC 2021 , Edited by admin on Fri Jun 25 21:17:15 UTC 2021
PRIMARY
EVMPD
SUB05743MIG
Created by admin on Fri Jun 25 21:17:15 UTC 2021 , Edited by admin on Fri Jun 25 21:17:15 UTC 2021
PRIMARY
RXCUI
1385
Created by admin on Fri Jun 25 21:17:15 UTC 2021 , Edited by admin on Fri Jun 25 21:17:15 UTC 2021
PRIMARY RxNorm
NCI_THESAURUS
C74412
Created by admin on Fri Jun 25 21:17:15 UTC 2021 , Edited by admin on Fri Jun 25 21:17:15 UTC 2021
PRIMARY
INN
1427
Created by admin on Fri Jun 25 21:17:15 UTC 2021 , Edited by admin on Fri Jun 25 21:17:15 UTC 2021
PRIMARY
MESH
D001553
Created by admin on Fri Jun 25 21:17:15 UTC 2021 , Edited by admin on Fri Jun 25 21:17:15 UTC 2021
PRIMARY