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Details

Stereochemistry ACHIRAL
Molecular Formula C27H29N5O6S
Molecular Weight 551.6162
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of BOSENTAN ANHYDROUS

SMILES

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

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 551.6162
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
Bosentan reduces blood pressure and the target-organ damage induced by a high-fructose diet in rats.
1999 Dec
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 endothelin antagonist bosentan inhibits the canalicular bile salt export pump: a potential mechanism for hepatic adverse reactions.
2001 Apr
Pharmacologic characterization of S-1255, a highly potent and orally active endothelin A receptor antagonist.
2001 Apr
Improvement of respiratory function by bosentan during endotoxic shock in the pig.
2001 Aug
Endothelin receptor blockade reduces ventricular dysfunction and injury after reoxygenation.
2001 Aug
Endothelin blockade in angiotensin II hypertension: prevention and treatment studies in the rat.
2001 Dec
Small bowel review: diseases of the small intestine.
2001 Dec
Endothelin and heart failure.
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
Augmentation of endothelial function by endothelin antagonism in human saphenous vein conduits.
2001 Feb
Endothelin synthesis and receptors in porcine kidney.
2001 Jan
Endothelin receptor blockade improves endothelial function in human internal mammary arteries.
2001 Jan
New pharmacological strategies for the treatment of heart failure.
2001 Jul
Long-term endothelin receptor blockade improves cardiovascular function in diabetes.
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
Aminoethyl-isothiourea inhibits the increase in plasma endothelin-1 caused by serogroup A streptococci and prolongs survival in rat peritoneal sepsis.
2001 Jun
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
Endothelin receptor antagonists in congestive heart failure: a new therapeutic principle for the future?
2001 May
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 dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomized placebo-controlled study].
2001 Nov
Rationale and perspective of endothelin-1 antagonism in acute heart failure.
2001 Nov
Renal tubulointerstitial damage caused by persistent proteinuria is attenuated in AT1-deficient mice: role of endothelin-1.
2001 Nov
Endothelin-1 decreases glutamate uptake in primary cultured rat astrocytes.
2001 Nov
Endothelin mediates phospholipase C stimulation in the proximal tubule during initiation of compensatory renal growth in adult rats.
2001 Oct
Endothelin-receptor antagonists in pulmonary hypertension.
2001 Oct 6
Ovarian hormones modulate endothelin-1 vascular reactivity and mRNA expression in DOCA-salt hypertensive rats.
2001 Sep
In vivo and in vitro studies exploring the pharmacokinetic interaction between bosentan, a dual endothelin receptor antagonist, and glyburide.
2002 Apr
Bosentan (Tracleer) for pulmonary arterial hypertension.
2002 Apr 1
Medical management of primary pulmonary hypertension.
2002 Feb
Endothelin antagonists and heart failure.
2002 Feb
Human endothelin subtype A receptor enhancement during tissue culture via de novo transcription.
2002 Jan
Hyperhexosemia induced functional and structural changes in the kidneys: role of endothelins.
2002 Jan
[The effects of endothelin blockade on renal expression of angiotensin II type 1 receptor in diabetic hypertensive rats].
2002 Jan 10
Tracleer (bosentan).
2002 Jan-Feb
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 12:43:47 UTC 2021
Edited
by admin
on Sat Jun 26 12:43:47 UTC 2021
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 Sat Jun 26 12:43:48 UTC 2021 , Edited by admin on Sat Jun 26 12:43:48 UTC 2021
NDF-RT N0000175364
Created by admin on Sat Jun 26 12:43:48 UTC 2021 , Edited by admin on Sat Jun 26 12:43:48 UTC 2021
WHO-ATC C02KX01
Created by admin on Sat Jun 26 12:43:48 UTC 2021 , Edited by admin on Sat Jun 26 12:43:48 UTC 2021
Code System Code Type Description
NCI_THESAURUS
C81107
Created by admin on Sat Jun 26 12:43:48 UTC 2021 , Edited by admin on Sat Jun 26 12:43:48 UTC 2021
PRIMARY
CAS
147536-97-8
Created by admin on Sat Jun 26 12:43:48 UTC 2021 , Edited by admin on Sat Jun 26 12:43:48 UTC 2021
PRIMARY
MERCK INDEX
M2625
Created by admin on Sat Jun 26 12:43:48 UTC 2021 , Edited by admin on Sat Jun 26 12:43:48 UTC 2021
PRIMARY Merck Index
EVMPD
SUB05877MIG
Created by admin on Sat Jun 26 12:43:48 UTC 2021 , Edited by admin on Sat Jun 26 12:43:48 UTC 2021
PRIMARY
EVMPD
SUB25414
Created by admin on Sat Jun 26 12:43:48 UTC 2021 , Edited by admin on Sat Jun 26 12:43:48 UTC 2021
PRIMARY
EPA CompTox
147536-97-8
Created by admin on Sat Jun 26 12:43:48 UTC 2021 , Edited by admin on Sat Jun 26 12:43:48 UTC 2021
PRIMARY
DRUG BANK
DB00559
Created by admin on Sat Jun 26 12:43:48 UTC 2021 , Edited by admin on Sat Jun 26 12:43:48 UTC 2021
PRIMARY
FDA UNII
XUL93R30K2
Created by admin on Sat Jun 26 12:43:48 UTC 2021 , Edited by admin on Sat Jun 26 12:43:48 UTC 2021
PRIMARY
RXCUI
1468845
Created by admin on Sat Jun 26 12:43:48 UTC 2021 , Edited by admin on Sat Jun 26 12:43:48 UTC 2021
PRIMARY RxNorm
PUBCHEM
104865
Created by admin on Sat Jun 26 12:43:48 UTC 2021 , Edited by admin on Sat Jun 26 12:43:48 UTC 2021
PRIMARY
INN
7195
Created by admin on Sat Jun 26 12:43:48 UTC 2021 , Edited by admin on Sat Jun 26 12:43:48 UTC 2021
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
BINDER->LIGAND
BINDING
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