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Details

Stereochemistry ACHIRAL
Molecular Formula C27H29N5O6S
Molecular Weight 551.614
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of BOSENTAN ANHYDROUS

SMILES

COC1=C(OC2=C(NS(=O)(=O)C3=CC=C(C=C3)C(C)(C)C)N=C(N=C2OCCO)C4=NC=CC=N4)C=CC=C1

InChI

InChIKey=GJPICJJJRGTNOD-UHFFFAOYSA-N
InChI=1S/C27H29N5O6S/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)

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

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
Differential effects of the mixed ET(A)/ET(B)-receptor antagonist bosentan on endothelin-induced bronchoconstriction, vasoconstriction and prostacyclin release.
2000 Aug
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
Activation of NF-kappaB in tubular epithelial cells of rats with intense proteinuria: role of angiotensin II and endothelin-1.
2001 Apr
Role of endothelin and vasopressin in DOCA-salt hypertension.
2001 Apr
Endothelin blockade in angiotensin II hypertension: prevention and treatment studies in the rat.
2001 Dec
Pulmonary hypertension associated with COPD.
2001 Dec
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
Role of endogenous endothelin on coronary reflow after cardioplegic arrest.
2001 Dec
Endothelin antagonist reduces hemodynamic responses to vasopressin in DOCA-salt hypertension.
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
Combined blockade of endothelin-1 and thromboxane A(2) receptors against postischaemic contractile dysfunction in rat hearts.
2001 Jan
Important role for endothelins in acute hepatic ischemia/reperfusion injury.
2001 Jan-Feb
New pharmacological strategies for the treatment of heart failure.
2001 Jul
Long-term endothelin receptor blockade improves cardiovascular function in diabetes.
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
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
Perceived benefit after participating in positive or negative/neutral heart failure trials: the patients' perspective.
2001 Mar
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
Neurogenic inflammation in the context of migraine.
2001 May 1
Acute endothelin a receptor blockade in heart failure.
2001 May 8
Bosentan, an endothelin antagonist, augments hepatic graft function by reducing graft circulatory impairment following ischemia/reperfusion injury.
2001 May-Jun
Effects of the endothelin receptor antagonist bosentan on cardiac performance during porcine endotoxin shock.
2001 Nov
Report from the 93rd Cardiovascular and Renal Drugs Advisory Committee Meeting, August 9-10, 2001.
2001 Oct 9
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
Tracleer. Tablets ease symptoms of rare lung disorder.
2002 Feb
Medical management of primary pulmonary hypertension.
2002 Feb
Crosstalk of endothelin-1 and platelet-derived growth factor in cardiac allograft arteriosclerosis.
2002 Feb 20
Endothelin is an important determinant of renal function in a rat model of acute liver and renal failure.
2002 Jan
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
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 Wed Jul 05 23:16:42 UTC 2023
Edited
by admin
on Wed Jul 05 23:16:42 UTC 2023
Record UNII
XUL93R30K2
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
BOSENTAN ANHYDROUS
Common Name English
BOSENTAN [MI]
Common Name English
ANHYDROUS BOSENTAN
Common Name English
bosentan [INN]
Common Name English
P-TERT-BUTYL-N-(6-(2-HYDROXYETHOXY)-5-(O-METHOXYPHENOXY)-2-(2-PYRIMIDINYL)-4-PYRIMIDINYL)BENZENESULFONAMIDE
Common Name English
Bosentan [WHO-DD]
Common Name English
BENZENESULFONAMIDE, 4-(1,1-DIMETHYLETHYL)-N-(6-(2-HYDROXYETHOXY)-5-(2-METHOXYPHENOXY)(2,2'-BIPYRIMIDIN)-4-YL)-
Systematic Name English
Classification Tree Code System Code
NDF-RT N0000175581
Created by admin on Wed Jul 05 23:16:42 UTC 2023 , Edited by admin on Wed Jul 05 23:16:42 UTC 2023
NDF-RT N0000175364
Created by admin on Wed Jul 05 23:16:42 UTC 2023 , Edited by admin on Wed Jul 05 23:16:42 UTC 2023
WHO-ATC C02KX01
Created by admin on Wed Jul 05 23:16:42 UTC 2023 , Edited by admin on Wed Jul 05 23:16:42 UTC 2023
Code System Code Type Description
NCI_THESAURUS
C81107
Created by admin on Wed Jul 05 23:16:42 UTC 2023 , Edited by admin on Wed Jul 05 23:16:42 UTC 2023
PRIMARY
CAS
147536-97-8
Created by admin on Wed Jul 05 23:16:42 UTC 2023 , Edited by admin on Wed Jul 05 23:16:42 UTC 2023
PRIMARY
MERCK INDEX
M2625
Created by admin on Wed Jul 05 23:16:42 UTC 2023 , Edited by admin on Wed Jul 05 23:16:42 UTC 2023
PRIMARY Merck Index
EVMPD
SUB05877MIG
Created by admin on Wed Jul 05 23:16:42 UTC 2023 , Edited by admin on Wed Jul 05 23:16:42 UTC 2023
PRIMARY
EVMPD
SUB25414
Created by admin on Wed Jul 05 23:16:42 UTC 2023 , Edited by admin on Wed Jul 05 23:16:42 UTC 2023
PRIMARY
CHEBI
51450
Created by admin on Wed Jul 05 23:16:42 UTC 2023 , Edited by admin on Wed Jul 05 23:16:42 UTC 2023
PRIMARY
EPA CompTox
DTXSID7046627
Created by admin on Wed Jul 05 23:16:42 UTC 2023 , Edited by admin on Wed Jul 05 23:16:42 UTC 2023
PRIMARY
DRUG BANK
DB00559
Created by admin on Wed Jul 05 23:16:42 UTC 2023 , Edited by admin on Wed Jul 05 23:16:42 UTC 2023
PRIMARY
FDA UNII
XUL93R30K2
Created by admin on Wed Jul 05 23:16:42 UTC 2023 , Edited by admin on Wed Jul 05 23:16:42 UTC 2023
PRIMARY
DAILYMED
XUL93R30K2
Created by admin on Wed Jul 05 23:16:42 UTC 2023 , Edited by admin on Wed Jul 05 23:16:42 UTC 2023
PRIMARY
RXCUI
1468845
Created by admin on Wed Jul 05 23:16:42 UTC 2023 , Edited by admin on Wed Jul 05 23:16:42 UTC 2023
PRIMARY RxNorm
PUBCHEM
104865
Created by admin on Wed Jul 05 23:16:42 UTC 2023 , Edited by admin on Wed Jul 05 23:16:42 UTC 2023
PRIMARY
SMS_ID
100000085262
Created by admin on Wed Jul 05 23:16:42 UTC 2023 , Edited by admin on Wed Jul 05 23:16:42 UTC 2023
PRIMARY
INN
7195
Created by admin on Wed Jul 05 23:16:42 UTC 2023 , Edited by admin on Wed Jul 05 23:16:42 UTC 2023
PRIMARY
Related Record Type Details
EXCRETED UNCHANGED
INTRAVENOUS ADMINISTRATION
AMOUNT EXCRETED
URINE
EXCRETED UNCHANGED
ORAL ADMINISTRATION
AMOUNT EXCRETED
FECAL
METABOLIC ENZYME -> SUBSTRATE
MAJOR
SALT/SOLVATE -> PARENT
METABOLIC ENZYME -> SUBSTRATE
MAJOR
SOLVATE->ANHYDROUS
BINDER->LIGAND
BINDING
Related Record Type Details
METABOLITE ACTIVE -> PARENT
Major metabolite.
MAJOR
FECAL; PLASMA; URINE
METABOLITE -> PARENT
METABOLITE -> PARENT
Minor metabolite.
MINOR
FECAL; PLASMA; URINE
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC
Tmax PHARMACOKINETIC ORAL ADMINISTRATION

SINGLE DOSE

Biological Half-life PHARMACOKINETIC