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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
Influence of several methodological procedures utilized to obtain in vitro vascular preparations on endothelial activity.
2001
Current management of primary pulmonary hypertension.
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
The loop diuretic torasemide interferes with endothelin-1 actions in the aorta of hypertensive rats.
2001
Activation of NF-kappaB in tubular epithelial cells of rats with intense proteinuria: role of angiotensin II and endothelin-1.
2001 Apr
Pharmacologic characterization of S-1255, a highly potent and orally active endothelin A receptor antagonist.
2001 Apr
Endothelin antagonist reduces hemodynamic responses to vasopressin in DOCA-salt hypertension.
2001 Dec
Therapeutic role of bosentan in hypertension: lessons from the model of perinephritic hypertension.
2001 Dec
Regression of renal vascular fibrosis by endothelin receptor antagonism.
2001 Feb
Augmentation of endothelial function by endothelin antagonism in human saphenous vein conduits.
2001 Feb
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
Neurogenic inflammation in the context of migraine.
2001 May 1
Bosentan, an endothelin antagonist, augments hepatic graft function by reducing graft circulatory impairment following ischemia/reperfusion injury.
2001 May-Jun
Potent and selective ET-A antagonists. 1. Syntheses and structure-activity relationships of N-(6-(2-(aryloxy)ethoxy)-4-pyrimidinyl)sulfonamide derivatives.
2001 Oct 11
Endothelin receptor blockade in congestive heart failure.
2001 Oct 30
Report from the 93rd Cardiovascular and Renal Drugs Advisory Committee Meeting, August 9-10, 2001.
2001 Oct 9
Ovarian hormones modulate endothelin-1 vascular reactivity and mRNA expression in DOCA-salt hypertensive rats.
2001 Sep
Growth factors in idiopathic pulmonary fibrosis: relative roles.
2002
Hyperhexosemia induced functional and structural changes in the kidneys: role of endothelins.
2002 Jan
[Physical endurance improves markedly. New therapy approach in pulmonary hypertension].
2002 Jan 17
Tracleer (bosentan).
2002 Jan-Feb
Influence of food intake and formulation on the pharmacokinetics and metabolism of bosentan, a dual endothelin receptor antagonist.
2002 Mar
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 Fri Dec 16 17:27:53 UTC 2022
Edited
by admin
on Fri Dec 16 17:27:53 UTC 2022
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 Fri Dec 16 17:27:53 UTC 2022 , Edited by admin on Fri Dec 16 17:27:53 UTC 2022
WHO-VATC QC02KX01
Created by admin on Fri Dec 16 17:27:53 UTC 2022 , Edited by admin on Fri Dec 16 17:27:53 UTC 2022
FDA ORPHAN DRUG 134200
Created by admin on Fri Dec 16 17:27:53 UTC 2022 , Edited by admin on Fri Dec 16 17:27:53 UTC 2022
LIVERTOX NBK547999
Created by admin on Fri Dec 16 17:27:53 UTC 2022 , Edited by admin on Fri Dec 16 17:27:53 UTC 2022
EMA ASSESSMENT REPORTS STAYVEER (AUTHORIZED SCLERODERMA, SYSTEMIC
Created by admin on Fri Dec 16 17:27:53 UTC 2022 , Edited by admin on Fri Dec 16 17:27:53 UTC 2022
WHO-ATC C02KX01
Created by admin on Fri Dec 16 17:27:53 UTC 2022 , Edited by admin on Fri Dec 16 17:27:53 UTC 2022
EMA ASSESSMENT REPORTS TRACLEER (AUTHORIZED: PLUMONARY HYPERTENSION, SYSTEMATIC SCLERODERMA)
Created by admin on Fri Dec 16 17:27:53 UTC 2022 , Edited by admin on Fri Dec 16 17:27:53 UTC 2022
FDA ORPHAN DRUG 267608
Created by admin on Fri Dec 16 17:27:53 UTC 2022 , Edited by admin on Fri Dec 16 17:27:53 UTC 2022
FDA ORPHAN DRUG 292209
Created by admin on Fri Dec 16 17:27:53 UTC 2022 , Edited by admin on Fri Dec 16 17:27:53 UTC 2022
EU-Orphan Drug EU/3/03/139
Created by admin on Fri Dec 16 17:27:53 UTC 2022 , Edited by admin on Fri Dec 16 17:27:53 UTC 2022
Code System Code Type Description
MERCK INDEX
M2625
Created by admin on Fri Dec 16 17:27:53 UTC 2022 , Edited by admin on Fri Dec 16 17:27:53 UTC 2022
PRIMARY Merck Index
CAS
157212-55-0
Created by admin on Fri Dec 16 17:27:53 UTC 2022 , Edited by admin on Fri Dec 16 17:27:53 UTC 2022
PRIMARY
LACTMED
Bosentan
Created by admin on Fri Dec 16 17:27:53 UTC 2022 , Edited by admin on Fri Dec 16 17:27:53 UTC 2022
PRIMARY
PUBCHEM
185462
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PRIMARY
RXCUI
498193
Created by admin on Fri Dec 16 17:27:53 UTC 2022 , Edited by admin on Fri Dec 16 17:27:53 UTC 2022
ALTERNATIVE
USAN
HH-16
Created by admin on Fri Dec 16 17:27:53 UTC 2022 , Edited by admin on Fri Dec 16 17:27:53 UTC 2022
PRIMARY
RS_ITEM_NUM
1076115
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PRIMARY
EVMPD
SUB22249
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PRIMARY
DAILYMED
Q326023R30
Created by admin on Fri Dec 16 17:27:53 UTC 2022 , Edited by admin on Fri Dec 16 17:27:53 UTC 2022
PRIMARY
IUPHAR
3494
Created by admin on Fri Dec 16 17:27:53 UTC 2022 , Edited by admin on Fri Dec 16 17:27:53 UTC 2022
PRIMARY
EPA CompTox
DTXSID80873178
Created by admin on Fri Dec 16 17:27:53 UTC 2022 , Edited by admin on Fri Dec 16 17:27:53 UTC 2022
PRIMARY
WIKIPEDIA
BOSENTAN
Created by admin on Fri Dec 16 17:27:53 UTC 2022 , Edited by admin on Fri Dec 16 17:27:53 UTC 2022
PRIMARY
CHEBI
51450
Created by admin on Fri Dec 16 17:27:53 UTC 2022 , Edited by admin on Fri Dec 16 17:27:53 UTC 2022
PRIMARY
RXCUI
75207
Created by admin on Fri Dec 16 17:27:53 UTC 2022 , Edited by admin on Fri Dec 16 17:27:53 UTC 2022
PRIMARY
DRUG CENTRAL
392
Created by admin on Fri Dec 16 17:27:53 UTC 2022 , Edited by admin on Fri Dec 16 17:27:53 UTC 2022
PRIMARY
FDA UNII
Q326023R30
Created by admin on Fri Dec 16 17:27:53 UTC 2022 , Edited by admin on Fri Dec 16 17:27:53 UTC 2022
PRIMARY
MESH
C086232
Created by admin on Fri Dec 16 17:27:53 UTC 2022 , Edited by admin on Fri Dec 16 17:27:53 UTC 2022
PRIMARY
NCI_THESAURUS
C47417
Created by admin on Fri Dec 16 17:27:53 UTC 2022 , Edited by admin on Fri Dec 16 17:27:53 UTC 2022
PRIMARY
DRUG BANK
DB00559
Created by admin on Fri Dec 16 17:27:53 UTC 2022 , Edited by admin on Fri Dec 16 17:27:53 UTC 2022
PRIMARY
ChEMBL
CHEMBL957
Created by admin on Fri Dec 16 17:27:53 UTC 2022 , Edited by admin on Fri Dec 16 17:27:53 UTC 2022
PRIMARY
Related Record Type Details
BINDER->LIGAND
BINDING
PARENT -> SALT/SOLVATE
TRANSPORTER -> INHIBITOR
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