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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 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 551.614
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
Adrenocorticotrophic hormone-induced hypertension in the rat: effects of the endothelin antagonist bosentan.
1999 Aug
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
Endothelin receptor blockade reduces ventricular dysfunction and injury after reoxygenation.
2001 Aug
Angiotensin II activates collagen type I gene in the renal cortex and aorta of transgenic mice through interaction with endothelin and TGF-beta.
2001 Dec
Endothelin and heart failure.
2001 Dec
Endothelin antagonism in experimental ischemic heart failure: hemodynamic, structural and neurohumoral effects.
2001 Dec
Coronary and aortic vasoreactivity protection with endothelin receptor antagonist, bosentan, after ischemia and hypoxia in aged rats.
2001 Dec 7
Endothelin antagonism uncovers insulin-mediated vasorelaxation in vitro and in vivo.
2001 Feb
Pressure overload increases GATA4 binding activity via endothelin-1.
2001 Feb 6
New pharmacological strategies for the treatment of heart failure.
2001 Jul
Endothelin mediates some of the renal actions of acutely administered angiotensin II.
2001 Jul
Aminoethyl-isothiourea inhibits the increase in plasma endothelin-1 caused by serogroup A streptococci and prolongs survival in rat peritoneal sepsis.
2001 Jun
Perceived benefit after participating in positive or negative/neutral heart failure trials: the patients' perspective.
2001 Mar
Subarachnoid haemorrhage-induced sympathoexcitation in rats is reversed by bosentan or sodium nitroprusside.
2001 Mar
A new era in the treatment of primary pulmonary hypertension.
2001 Mar
The timing of endothelin and nitric oxide inhibition affects survival in a mice model of septic shock.
2001 Mar 2
Endothelin receptor antagonists in congestive heart failure: a new therapeutic principle for the future?
2001 May
Effects of the endothelin receptor antagonist bosentan on cardiac performance during porcine endotoxin shock.
2001 Nov
Endothelin mediates phospholipase C stimulation in the proximal tubule during initiation of compensatory renal growth in adult rats.
2001 Oct
Tracleer. Tablets ease symptoms of rare lung disorder.
2002 Feb
Endothelin antagonists and heart failure.
2002 Feb
Crosstalk of endothelin-1 and platelet-derived growth factor in cardiac allograft arteriosclerosis.
2002 Feb 20
Human endothelin subtype A receptor enhancement during tissue culture via de novo transcription.
2002 Jan
Direct left ventricular wall stretch activates GATA4 binding in perfused rat heart: involvement of autocrine/paracrine pathways.
2002 Jan
Hyperhexosemia induced functional and structural changes in the kidneys: role of endothelins.
2002 Jan
[Bosentan in pulmonary hypertension].
2002 Mar
Chronic endothelin receptor blockade prevents renal vasoconstriction and sodium retention in rats with chronic heart failure.
2002 Mar
Influence of food intake and formulation on the pharmacokinetics and metabolism of bosentan, a dual endothelin receptor antagonist.
2002 Mar
Treatment of primary pulmonary hypertension -- the next generation.
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 Wed Jul 05 23:03:21 UTC 2023
Edited
by admin
on Wed Jul 05 23:03:21 UTC 2023
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
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 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 Wed Jul 05 23:03:21 UTC 2023 , Edited by admin on Wed Jul 05 23:03:21 UTC 2023
WHO-VATC QC02KX01
Created by admin on Wed Jul 05 23:03:21 UTC 2023 , Edited by admin on Wed Jul 05 23:03:21 UTC 2023
FDA ORPHAN DRUG 134200
Created by admin on Wed Jul 05 23:03:21 UTC 2023 , Edited by admin on Wed Jul 05 23:03:21 UTC 2023
LIVERTOX NBK547999
Created by admin on Wed Jul 05 23:03:21 UTC 2023 , Edited by admin on Wed Jul 05 23:03:21 UTC 2023
EMA ASSESSMENT REPORTS STAYVEER (AUTHORIZED SCLERODERMA, SYSTEMIC
Created by admin on Wed Jul 05 23:03:21 UTC 2023 , Edited by admin on Wed Jul 05 23:03:21 UTC 2023
WHO-ATC C02KX01
Created by admin on Wed Jul 05 23:03:21 UTC 2023 , Edited by admin on Wed Jul 05 23:03:21 UTC 2023
EMA ASSESSMENT REPORTS TRACLEER (AUTHORIZED: PLUMONARY HYPERTENSION, SYSTEMATIC SCLERODERMA)
Created by admin on Wed Jul 05 23:03:21 UTC 2023 , Edited by admin on Wed Jul 05 23:03:21 UTC 2023
FDA ORPHAN DRUG 267608
Created by admin on Wed Jul 05 23:03:21 UTC 2023 , Edited by admin on Wed Jul 05 23:03:21 UTC 2023
FDA ORPHAN DRUG 292209
Created by admin on Wed Jul 05 23:03:21 UTC 2023 , Edited by admin on Wed Jul 05 23:03:21 UTC 2023
EU-Orphan Drug EU/3/03/139
Created by admin on Wed Jul 05 23:03:21 UTC 2023 , Edited by admin on Wed Jul 05 23:03:21 UTC 2023
Code System Code Type Description
MERCK INDEX
M2625
Created by admin on Wed Jul 05 23:03:21 UTC 2023 , Edited by admin on Wed Jul 05 23:03:21 UTC 2023
PRIMARY Merck Index
CAS
157212-55-0
Created by admin on Wed Jul 05 23:03:21 UTC 2023 , Edited by admin on Wed Jul 05 23:03:21 UTC 2023
PRIMARY
LACTMED
Bosentan
Created by admin on Wed Jul 05 23:03:21 UTC 2023 , Edited by admin on Wed Jul 05 23:03:21 UTC 2023
PRIMARY
PUBCHEM
185462
Created by admin on Wed Jul 05 23:03:21 UTC 2023 , Edited by admin on Wed Jul 05 23:03:21 UTC 2023
PRIMARY
RXCUI
498193
Created by admin on Wed Jul 05 23:03:21 UTC 2023 , Edited by admin on Wed Jul 05 23:03:21 UTC 2023
ALTERNATIVE
USAN
HH-16
Created by admin on Wed Jul 05 23:03:21 UTC 2023 , Edited by admin on Wed Jul 05 23:03:21 UTC 2023
PRIMARY
RS_ITEM_NUM
1076115
Created by admin on Wed Jul 05 23:03:21 UTC 2023 , Edited by admin on Wed Jul 05 23:03:21 UTC 2023
PRIMARY
EVMPD
SUB22249
Created by admin on Wed Jul 05 23:03:21 UTC 2023 , Edited by admin on Wed Jul 05 23:03:21 UTC 2023
PRIMARY
DAILYMED
Q326023R30
Created by admin on Wed Jul 05 23:03:21 UTC 2023 , Edited by admin on Wed Jul 05 23:03:21 UTC 2023
PRIMARY
SMS_ID
100000091512
Created by admin on Wed Jul 05 23:03:21 UTC 2023 , Edited by admin on Wed Jul 05 23:03:21 UTC 2023
PRIMARY
IUPHAR
3494
Created by admin on Wed Jul 05 23:03:21 UTC 2023 , Edited by admin on Wed Jul 05 23:03:21 UTC 2023
PRIMARY
EPA CompTox
DTXSID80873178
Created by admin on Wed Jul 05 23:03:21 UTC 2023 , Edited by admin on Wed Jul 05 23:03:21 UTC 2023
PRIMARY
WIKIPEDIA
BOSENTAN
Created by admin on Wed Jul 05 23:03:21 UTC 2023 , Edited by admin on Wed Jul 05 23:03:21 UTC 2023
PRIMARY
CHEBI
51450
Created by admin on Wed Jul 05 23:03:21 UTC 2023 , Edited by admin on Wed Jul 05 23:03:21 UTC 2023
PRIMARY
RXCUI
75207
Created by admin on Wed Jul 05 23:03:21 UTC 2023 , Edited by admin on Wed Jul 05 23:03:21 UTC 2023
PRIMARY
DRUG CENTRAL
392
Created by admin on Wed Jul 05 23:03:21 UTC 2023 , Edited by admin on Wed Jul 05 23:03:21 UTC 2023
PRIMARY
FDA UNII
Q326023R30
Created by admin on Wed Jul 05 23:03:21 UTC 2023 , Edited by admin on Wed Jul 05 23:03:21 UTC 2023
PRIMARY
MESH
C086232
Created by admin on Wed Jul 05 23:03:21 UTC 2023 , Edited by admin on Wed Jul 05 23:03:21 UTC 2023
PRIMARY
NCI_THESAURUS
C47417
Created by admin on Wed Jul 05 23:03:21 UTC 2023 , Edited by admin on Wed Jul 05 23:03:21 UTC 2023
PRIMARY
DRUG BANK
DB00559
Created by admin on Wed Jul 05 23:03:21 UTC 2023 , Edited by admin on Wed Jul 05 23:03:21 UTC 2023
PRIMARY
ChEMBL
CHEMBL957
Created by admin on Wed Jul 05 23:03:21 UTC 2023 , Edited by admin on Wed Jul 05 23:03:21 UTC 2023
PRIMARY
Related Record Type Details
BINDER->LIGAND
BINDING
TRANSPORTER -> INHIBITOR
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