U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C27H29N5O6S.H2O
Molecular Weight 569.6315
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of BOSENTAN

SMILES

CC(C)(C)c1ccc(cc1)S(=O)(=O)Nc2c(c(nc(-c3ncccn3)n2)OCCO)Oc4ccccc4OC.O

InChI

InChIKey=SXTRWVVIEPWAKM-UHFFFAOYSA-N
InChI=1S/C27H29N5O6S.H2O/c1-27(2,3)18-10-12-19(13-11-18)39(34,35)32-23-22(38-21-9-6-5-8-20(21)36-4)26(37-17-16-33)31-25(30-23)24-28-14-7-15-29-24;/h5-15,33H,16-17H2,1-4H3,(H,30,31,32);1H2

HIDE SMILES / InChI

Molecular Formula H2O
Molecular Weight 18.0153
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C27H29N5O6S
Molecular Weight 551.6162
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Bosentan is a dual endothelin receptor antagonist important in the treatment of pulmonary artery hypertension (PAH). It is licensed in the United States, the European Union and other countries by Actelion Pharmaceuticals for the management of PAH under the trade name Tracleer®. Bosentan is used to treat pulmonary hypertension by blocking the action of endothelin molecules that would otherwise promote narrowing of the blood vessels and lead to high blood pressure. Bosentan competitively antagonizes the binding of 125I-labeled ET-1 to human vascular smooth muscle cells (predominantly ETA receptors) with an inhibition constant (Ki ) of 4.7 nM and to human placenta membranes (predominantly ETB receptors) with a Ki of 95 nM. Furthermore, bosentan is specific for endothelin receptors and does not interfere with the binding of a variety of peptides, neurotransmitters, growth factors, or eicosanoids to their receptors.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
TRACLEER

Approved Use

Tracleer is an endothelin receptor antagonist indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve exercise ability and to decrease clinical worsening. Studies establishing effectiveness included predominantly patients with NYHA Functional Class II-IV symptoms and etiologies of idiopathic or heritable PAH (60%), PAH associated with connective tissue diseases (21%), and PAH associated with congenital heart disease with left-to-right shunts (18%) (1.1). Considerations for use: Consider whether benefits offset the risk of hepatotoxicity in WHO Class II patients. Early hepatotoxicity may preclude future use as disease progresses (1.1). 1.1 Pulmonary Arterial Hypertension Tracleer® is indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve exercise ability and to decrease clinical worsening. Studies establishing effectiveness included predominantly patients with NYHA Functional Class II-IV symptoms and etiologies of idiopathic or heritable PAH (60%), PAH associated with connective tissue diseases (21%), and PAH associated with congenital heart disease with left-to-right shunts (18%) [see Clinical Studies (14.1)

Launch Date

1.00621438E12
PubMed

PubMed

TitleDatePubMed
Endothelin antagonism with bosentan: a review of potential applications.
1999 Apr
Endothelin receptor antagonist activity of (R)-(-)-2-(benzo[1,3]dioxol-5-yl)-N-(4-isopropylphenylsulfonyl)-2-(6-methyl- 2-propylpyridin-3-yloxy)acetamide hydrochloride (PABSA) in rat aortic smooth muscle cells and isolated rat thoracic aorta.
2001
The loop diuretic torasemide interferes with endothelin-1 actions in the aorta of hypertensive rats.
2001
Chronic bosentan treatment improves renal artery vascular function in diabetes.
2001 Apr
The endothelin antagonist bosentan inhibits the canalicular bile salt export pump: a potential mechanism for hepatic adverse reactions.
2001 Apr
Effect of endothelin antagonism on the production of cytokines in eosinophilic airway inflammation.
2001 Apr
The underreporting of results and possible mechanisms of 'negative' drug trials in patients with chronic heart failure.
2001 Aug
Endothelin receptor blockade reduces ventricular dysfunction and injury after reoxygenation.
2001 Aug
Report From the 93rd Cardiovascular and Renal Drugs Advisory Committee Meeting, August 9-10, 2001.
2001 Aug 28
Pulmonary hypertension associated with COPD.
2001 Dec
Endothelin and heart failure.
2001 Dec
Hemodynamic effects of bosentan in patients with chronic heart failure.
2001 Dec
Endothelin antagonism in experimental ischemic heart failure: hemodynamic, structural and neurohumoral effects.
2001 Dec
Therapeutic role of bosentan in hypertension: lessons from the model of perinephritic hypertension.
2001 Dec
Role of endothelin and isoprostanes in slow pressor responses to angiotensin II.
2001 Feb
Regression of renal vascular fibrosis by endothelin receptor antagonism.
2001 Feb
Endothelin antagonism uncovers insulin-mediated vasorelaxation in vitro and in vivo.
2001 Feb
Combined blockade of endothelin-1 and thromboxane A(2) receptors against postischaemic contractile dysfunction in rat hearts.
2001 Jan
Endothelin receptor antagonist prevents parathyroid cell proliferation of low calcium diet-induced hyperparathyroidism in rats.
2001 Jan
Endothelin receptor blockade improves endothelial function in human internal mammary arteries.
2001 Jan
Long-term endothelin receptor blockade improves cardiovascular function in diabetes.
2001 Jul
Endothelin mediates some of the renal actions of acutely administered angiotensin II.
2001 Jul
Influence of nitric oxide synthase inhibition and endothelin-1 receptor blockade on acetylcholine-induced coronary artery contraction in vitro in dilated and ischemic cardiomyopathies.
2001 Jul
Effects of the endothelin receptor antagonist Bosentan on ischaemia/reperfusion injury in rat skeletal muscle.
2001 Jul 13
Differential effects of angiotensin II versus endothelin-1 inhibitions in hypertrophic left ventricular myocardium during transition to heart failure.
2001 Jul 31
Endothelium-dependent relaxation in response to low concentrations of bradykinin is enhanced by phosphoramidon, bosentan and BQ-123 in bovine coronary arteries in vitro.
2001 Jun
Aminoethyl-isothiourea inhibits the increase in plasma endothelin-1 caused by serogroup A streptococci and prolongs survival in rat peritoneal sepsis.
2001 Jun
The timing of endothelin and nitric oxide inhibition affects survival in a mice model of septic shock.
2001 Mar 2
Update in pharmacologic treatment of hypertension.
2001 May
Blockade of the renin-angiotensin and endothelin systems on progressive renal injury.
2001 May
Effects of the endothelin receptor antagonist bosentan on cardiac performance during porcine endotoxin shock.
2001 Nov
Renal tubulointerstitial damage caused by persistent proteinuria is attenuated in AT1-deficient mice: role of endothelin-1.
2001 Nov
Endothelin mediates phospholipase C stimulation in the proximal tubule during initiation of compensatory renal growth in adult rats.
2001 Oct
Ovarian hormones modulate endothelin-1 vascular reactivity and mRNA expression in DOCA-salt hypertensive rats.
2001 Sep
Endogenous endothelins mediate increased acidification in remnant kidneys.
2001 Sep
Growth factors in idiopathic pulmonary fibrosis: relative roles.
2002
Combined inhibition of neutral endopeptidase with angiotensin converting enzyme or endothelin converting enzyme in experimental diabetes.
2002 Apr
Bosentan (Tracleer) for pulmonary arterial hypertension.
2002 Apr 1
Tracleer. Tablets ease symptoms of rare lung disorder.
2002 Feb
Endothelin antagonists and heart failure.
2002 Feb
Human endothelin subtype A receptor enhancement during tissue culture via de novo transcription.
2002 Jan
Naftidrofuryl exerts antiserotonergic but no endothelin-receptor blocking effects in AS4.1 cells, juxtaglomerular cells and isolated perfused rat kidneys.
2002 Jan
[Bosentan in pulmonary hypertension].
2002 Mar
Bosentan enters market with risk management program.
2002 Mar 15
Patents

Sample Use Guides

Initiate at 62.5 mg twice daily with or without food for 4 weeks, and then increase to 125 mg twice daily
Route of Administration: Oral
In Vitro Use Guide
Curator's Comment:: In vitro, bosentan inhibits the contractions of isolated rat trachea induced by ET-1 in a concentration-dependent manner (1-100 uM). https://www.ncbi.nlm.nih.gov/pubmed/18729040
Competition studies show that, in the absence of human serum albumin, the IC50 value of Bosentan was 5.7 nM. Addition of increasing doses of human serum albumin incrementally decreased the potency of Bosentan to 122.7 nM.
Substance Class Chemical
Created
by admin
on Sat Jun 26 02:56:55 UTC 2021
Edited
by admin
on Sat Jun 26 02:56:55 UTC 2021
Record UNII
Q326023R30
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
BOSENTAN
ORANGE BOOK   USAN   USP-RS   VANDF  
USAN  
Official Name English
BOSENTAN [USP-RS]
Common Name English
BOSENTAN MONOHYDRATE [MI]
Common Name English
BOSENTAN MONOHYDRATE [WHO-DD]
Common Name English
RO-47-0203-029
Code English
P-TERT-BUTYL-N-(6-(2-HYDROXYETHOXY)-5-(O-METHOXYPHENOXY)-2-(2-PYRIMIDINYL)-4-PYRIMIDINYL)BENZENESULFONAMIDE MONOHYDRATE
Common Name English
BOSENTAN [USAN]
Common Name English
BOSENTAN MONOHYDRATE [EMA EPAR]
Common Name English
RO 47-0203/029
Code English
RO-470203029
Code English
TRACLEER
Brand Name English
BENZENESULFONAMIDE, 4-(1,1-DIMETHYLETHYL)-N-(6-(2-HYDROXYETHOXY)-5-(2-METHOXYPHENOXY)(2,2'BIPYRIMIDIN)-4-YL)-, MONOHYDRATE
Systematic Name English
BOSENTAN [VANDF]
Common Name English
BOSENTAN HYDRATE [JAN]
Common Name English
BOSENTAN [ORANGE BOOK]
Common Name English
BOSENTAN MONOHYDRATE
EMA EPAR   MI   WHO-DD  
Common Name English
BOSENTAN HYDRATE
JAN  
Common Name English
RO-47-0203/029
Code English
Classification Tree Code System Code
NDF-RT N0000175581
Created by admin on Sat Jun 26 02:56:55 UTC 2021 , Edited by admin on Sat Jun 26 02:56:55 UTC 2021
WHO-VATC QC02KX01
Created by admin on Sat Jun 26 02:56:55 UTC 2021 , Edited by admin on Sat Jun 26 02:56:55 UTC 2021
FDA ORPHAN DRUG 134200
Created by admin on Sat Jun 26 02:56:55 UTC 2021 , Edited by admin on Sat Jun 26 02:56:55 UTC 2021
LIVERTOX 119
Created by admin on Sat Jun 26 02:56:55 UTC 2021 , Edited by admin on Sat Jun 26 02:56:55 UTC 2021
EMA ASSESSMENT REPORTS STAYVEER (AUTHORIZED SCLERODERMA, SYSTEMIC
Created by admin on Sat Jun 26 02:56:55 UTC 2021 , Edited by admin on Sat Jun 26 02:56:55 UTC 2021
WHO-ATC C02KX01
Created by admin on Sat Jun 26 02:56:55 UTC 2021 , Edited by admin on Sat Jun 26 02:56:55 UTC 2021
EMA ASSESSMENT REPORTS TRACLEER (AUTHORIZED: PLUMONARY HYPERTENSION, SYSTEMATIC SCLERODERMA)
Created by admin on Sat Jun 26 02:56:55 UTC 2021 , Edited by admin on Sat Jun 26 02:56:55 UTC 2021
FDA ORPHAN DRUG 267608
Created by admin on Sat Jun 26 02:56:55 UTC 2021 , Edited by admin on Sat Jun 26 02:56:55 UTC 2021
FDA ORPHAN DRUG 292209
Created by admin on Sat Jun 26 02:56:55 UTC 2021 , Edited by admin on Sat Jun 26 02:56:55 UTC 2021
EU-Orphan Drug EU/3/03/139
Created by admin on Sat Jun 26 02:56:55 UTC 2021 , Edited by admin on Sat Jun 26 02:56:55 UTC 2021
Code System Code Type Description
MERCK INDEX
M2625
Created by admin on Sat Jun 26 02:56:55 UTC 2021 , Edited by admin on Sat Jun 26 02:56:55 UTC 2021
PRIMARY Merck Index
CAS
157212-55-0
Created by admin on Sat Jun 26 02:56:55 UTC 2021 , Edited by admin on Sat Jun 26 02:56:55 UTC 2021
PRIMARY
LACTMED
Bosentan
Created by admin on Sat Jun 26 02:56:55 UTC 2021 , Edited by admin on Sat Jun 26 02:56:55 UTC 2021
PRIMARY
PUBCHEM
185462
Created by admin on Sat Jun 26 02:56:55 UTC 2021 , Edited by admin on Sat Jun 26 02:56:55 UTC 2021
PRIMARY
RXCUI
498193
Created by admin on Sat Jun 26 02:56:55 UTC 2021 , Edited by admin on Sat Jun 26 02:56:55 UTC 2021
ALTERNATIVE
EVMPD
SUB22249
Created by admin on Sat Jun 26 02:56:55 UTC 2021 , Edited by admin on Sat Jun 26 02:56:55 UTC 2021
PRIMARY
IUPHAR
3494
Created by admin on Sat Jun 26 02:56:55 UTC 2021 , Edited by admin on Sat Jun 26 02:56:55 UTC 2021
PRIMARY
WIKIPEDIA
BOSENTAN
Created by admin on Sat Jun 26 02:56:55 UTC 2021 , Edited by admin on Sat Jun 26 02:56:55 UTC 2021
PRIMARY
RXCUI
75207
Created by admin on Sat Jun 26 02:56:55 UTC 2021 , Edited by admin on Sat Jun 26 02:56:55 UTC 2021
PRIMARY
DRUG CENTRAL
392
Created by admin on Sat Jun 26 02:56:55 UTC 2021 , Edited by admin on Sat Jun 26 02:56:55 UTC 2021
PRIMARY
FDA UNII
Q326023R30
Created by admin on Sat Jun 26 02:56:55 UTC 2021 , Edited by admin on Sat Jun 26 02:56:55 UTC 2021
PRIMARY
MESH
C086232
Created by admin on Sat Jun 26 02:56:55 UTC 2021 , Edited by admin on Sat Jun 26 02:56:55 UTC 2021
PRIMARY
NCI_THESAURUS
C47417
Created by admin on Sat Jun 26 02:56:55 UTC 2021 , Edited by admin on Sat Jun 26 02:56:55 UTC 2021
PRIMARY
USP_CATALOG
1076115
Created by admin on Sat Jun 26 02:56:55 UTC 2021 , Edited by admin on Sat Jun 26 02:56:55 UTC 2021
PRIMARY USP-RS
DRUG BANK
DB00559
Created by admin on Sat Jun 26 02:56:55 UTC 2021 , Edited by admin on Sat Jun 26 02:56:55 UTC 2021
PRIMARY
ChEMBL
CHEMBL957
Created by admin on Sat Jun 26 02:56:55 UTC 2021 , Edited by admin on Sat Jun 26 02:56:55 UTC 2021
PRIMARY
Related Record Type Details
TRANSPORTER -> INHIBITOR
BINDER->LIGAND
BINDING
PARENT -> SALT/SOLVATE
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC