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Details

Stereochemistry ACHIRAL
Molecular Formula C27H29N5O6S.H2O
Molecular Weight 569.629
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of BOSENTAN

SMILES

O.COC1=CC=CC=C1OC2=C(OCCO)N=C(N=C2NS(=O)(=O)C3=CC=C(C=C3)C(C)(C)C)C4=NC=CC=N4

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 C27H29N5O6S
Molecular Weight 551.614
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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

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

2001
PubMed

PubMed

TitleDatePubMed
Differential effects of the mixed ET(A)/ET(B)-receptor antagonist bosentan on endothelin-induced bronchoconstriction, vasoconstriction and prostacyclin release.
2000 Aug
Pharmacological regulation of postischemic sinusoidal diameters in rats--a new approach for reducing hepatic ischemia/reperfusion injury.
2001
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
Improvement of respiratory function by bosentan during endotoxic shock in the pig.
2001 Aug
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
Endothelin receptor antagonists in congestive heart failure: a new therapeutic principle for the future?
2001 May
Combined angiotensin and endothelin receptor blockade attenuates adverse cardiac remodeling post-myocardial infarction in the rat: possible role of transforming growth factor beta(1).
2001 May
Effects of the endothelin receptor antagonist bosentan on cardiac performance during porcine endotoxin shock.
2001 Nov
Endogenous endothelins mediate increased acidification in remnant kidneys.
2001 Sep
Growth factors in idiopathic pulmonary fibrosis: relative roles.
2002
In vivo and in vitro studies exploring the pharmacokinetic interaction between bosentan, a dual endothelin receptor antagonist, and glyburide.
2002 Apr
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
Direct left ventricular wall stretch activates GATA4 binding in perfused rat heart: involvement of autocrine/paracrine pathways.
2002 Jan
[The effects of endothelin blockade on renal expression of angiotensin II type 1 receptor in diabetic hypertensive rats].
2002 Jan 10
[Bosentan in pulmonary hypertension].
2002 Mar
Chronic endothelin receptor blockade prevents renal vasoconstriction and sodium retention in rats with chronic heart failure.
2002 Mar
Bosentan enters market with risk management program.
2002 Mar 15
Treatment of primary pulmonary hypertension -- the next generation.
2002 Mar 21
Bosentan therapy for pulmonary arterial hypertension.
2002 Mar 21
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 Mon Mar 31 18:01:21 GMT 2025
Edited
by admin
on Mon Mar 31 18:01:21 GMT 2025
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 MONOHYDRATE
EMA EPAR   MI   WHO-DD  
Preferred Name English
BOSENTAN [USP-RS]
Common Name English
BOSENTAN MONOHYDRATE [MI]
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 [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 Mon Mar 31 18:01:21 GMT 2025 , Edited by admin on Mon Mar 31 18:01:21 GMT 2025
WHO-VATC QC02KX01
Created by admin on Mon Mar 31 18:01:21 GMT 2025 , Edited by admin on Mon Mar 31 18:01:21 GMT 2025
FDA ORPHAN DRUG 134200
Created by admin on Mon Mar 31 18:01:21 GMT 2025 , Edited by admin on Mon Mar 31 18:01:21 GMT 2025
LIVERTOX NBK547999
Created by admin on Mon Mar 31 18:01:21 GMT 2025 , Edited by admin on Mon Mar 31 18:01:21 GMT 2025
EMA ASSESSMENT REPORTS STAYVEER (AUTHORIZED SCLERODERMA, SYSTEMIC
Created by admin on Mon Mar 31 18:01:21 GMT 2025 , Edited by admin on Mon Mar 31 18:01:21 GMT 2025
WHO-ATC C02KX01
Created by admin on Mon Mar 31 18:01:21 GMT 2025 , Edited by admin on Mon Mar 31 18:01:21 GMT 2025
EMA ASSESSMENT REPORTS TRACLEER (AUTHORIZED: PLUMONARY HYPERTENSION, SYSTEMATIC SCLERODERMA)
Created by admin on Mon Mar 31 18:01:21 GMT 2025 , Edited by admin on Mon Mar 31 18:01:21 GMT 2025
FDA ORPHAN DRUG 267608
Created by admin on Mon Mar 31 18:01:21 GMT 2025 , Edited by admin on Mon Mar 31 18:01:21 GMT 2025
FDA ORPHAN DRUG 292209
Created by admin on Mon Mar 31 18:01:21 GMT 2025 , Edited by admin on Mon Mar 31 18:01:21 GMT 2025
EU-Orphan Drug EU/3/03/139
Created by admin on Mon Mar 31 18:01:21 GMT 2025 , Edited by admin on Mon Mar 31 18:01:21 GMT 2025
Code System Code Type Description
MERCK INDEX
m2625
Created by admin on Mon Mar 31 18:01:21 GMT 2025 , Edited by admin on Mon Mar 31 18:01:21 GMT 2025
PRIMARY Merck Index
CAS
157212-55-0
Created by admin on Mon Mar 31 18:01:21 GMT 2025 , Edited by admin on Mon Mar 31 18:01:21 GMT 2025
PRIMARY
LACTMED
Bosentan
Created by admin on Mon Mar 31 18:01:21 GMT 2025 , Edited by admin on Mon Mar 31 18:01:21 GMT 2025
PRIMARY
PUBCHEM
185462
Created by admin on Mon Mar 31 18:01:21 GMT 2025 , Edited by admin on Mon Mar 31 18:01:21 GMT 2025
PRIMARY
RXCUI
498193
Created by admin on Mon Mar 31 18:01:21 GMT 2025 , Edited by admin on Mon Mar 31 18:01:21 GMT 2025
ALTERNATIVE
USAN
HH-16
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PRIMARY
RS_ITEM_NUM
1076115
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PRIMARY
EVMPD
SUB22249
Created by admin on Mon Mar 31 18:01:21 GMT 2025 , Edited by admin on Mon Mar 31 18:01:21 GMT 2025
PRIMARY
DAILYMED
Q326023R30
Created by admin on Mon Mar 31 18:01:21 GMT 2025 , Edited by admin on Mon Mar 31 18:01:21 GMT 2025
PRIMARY
SMS_ID
100000091512
Created by admin on Mon Mar 31 18:01:21 GMT 2025 , Edited by admin on Mon Mar 31 18:01:21 GMT 2025
PRIMARY
IUPHAR
3494
Created by admin on Mon Mar 31 18:01:21 GMT 2025 , Edited by admin on Mon Mar 31 18:01:21 GMT 2025
PRIMARY
EPA CompTox
DTXSID80873178
Created by admin on Mon Mar 31 18:01:21 GMT 2025 , Edited by admin on Mon Mar 31 18:01:21 GMT 2025
PRIMARY
WIKIPEDIA
BOSENTAN
Created by admin on Mon Mar 31 18:01:21 GMT 2025 , Edited by admin on Mon Mar 31 18:01:21 GMT 2025
PRIMARY
CHEBI
51450
Created by admin on Mon Mar 31 18:01:21 GMT 2025 , Edited by admin on Mon Mar 31 18:01:21 GMT 2025
PRIMARY
RXCUI
75207
Created by admin on Mon Mar 31 18:01:21 GMT 2025 , Edited by admin on Mon Mar 31 18:01:21 GMT 2025
PRIMARY
DRUG CENTRAL
392
Created by admin on Mon Mar 31 18:01:21 GMT 2025 , Edited by admin on Mon Mar 31 18:01:21 GMT 2025
PRIMARY
FDA UNII
Q326023R30
Created by admin on Mon Mar 31 18:01:21 GMT 2025 , Edited by admin on Mon Mar 31 18:01:21 GMT 2025
PRIMARY
MESH
C086232
Created by admin on Mon Mar 31 18:01:21 GMT 2025 , Edited by admin on Mon Mar 31 18:01:21 GMT 2025
PRIMARY
NCI_THESAURUS
C47417
Created by admin on Mon Mar 31 18:01:21 GMT 2025 , Edited by admin on Mon Mar 31 18:01:21 GMT 2025
PRIMARY
DRUG BANK
DB00559
Created by admin on Mon Mar 31 18:01:21 GMT 2025 , Edited by admin on Mon Mar 31 18:01:21 GMT 2025
PRIMARY
ChEMBL
CHEMBL957
Created by admin on Mon Mar 31 18:01:21 GMT 2025 , Edited by admin on Mon Mar 31 18:01:21 GMT 2025
PRIMARY
Related Record Type Details
TRANSPORTER -> INHIBITOR
BINDER->LIGAND
BINDING
PARENT -> SALT/SOLVATE
ANHYDROUS->SOLVATE
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC