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
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
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.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
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Target ID: CHEMBL2096678 |
|||
Target ID: CHEMBL4566 |
4.7 nM [Ki] | ||
Target ID: CHEMBL1785 |
95.0 nM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | TRACLEER Approved UseTracleer 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 Date1.00621438E12 |
PubMed
Title | Date | PubMed |
---|---|---|
Influence of several methodological procedures utilized to obtain in vitro vascular preparations on endothelial activity. | 2001 |
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Current management of primary pulmonary hypertension. | 2001 |
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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 |
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The loop diuretic torasemide interferes with endothelin-1 actions in the aorta of hypertensive rats. | 2001 |
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Activation of NF-kappaB in tubular epithelial cells of rats with intense proteinuria: role of angiotensin II and endothelin-1. | 2001 Apr |
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Pharmacologic characterization of S-1255, a highly potent and orally active endothelin A receptor antagonist. | 2001 Apr |
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Endothelin antagonist reduces hemodynamic responses to vasopressin in DOCA-salt hypertension. | 2001 Dec |
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Therapeutic role of bosentan in hypertension: lessons from the model of perinephritic hypertension. | 2001 Dec |
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Regression of renal vascular fibrosis by endothelin receptor antagonism. | 2001 Feb |
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Augmentation of endothelial function by endothelin antagonism in human saphenous vein conduits. | 2001 Feb |
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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 |
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Neurogenic inflammation in the context of migraine. | 2001 May 1 |
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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 |
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Report from the 93rd Cardiovascular and Renal Drugs Advisory Committee Meeting, August 9-10, 2001. | 2001 Oct 9 |
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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 |
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[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 |
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/8637410
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
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admin
on
Edited
Fri Dec 16 17:27:53 UTC 2022
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on
Fri Dec 16 17:27:53 UTC 2022
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Record UNII |
Q326023R30
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Record Status |
Validated (UNII)
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NDF-RT |
N0000175581
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WHO-VATC |
QC02KX01
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FDA ORPHAN DRUG |
134200
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LIVERTOX |
NBK547999
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EMA ASSESSMENT REPORTS |
STAYVEER (AUTHORIZED SCLERODERMA, SYSTEMIC
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WHO-ATC |
C02KX01
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EMA ASSESSMENT REPORTS |
TRACLEER (AUTHORIZED: PLUMONARY HYPERTENSION, SYSTEMATIC SCLERODERMA)
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FDA ORPHAN DRUG |
267608
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FDA ORPHAN DRUG |
292209
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EU-Orphan Drug |
EU/3/03/139
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157212-55-0
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Related Record | Type | Details | ||
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BINDER->LIGAND |
BINDING
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PARENT -> SALT/SOLVATE | |||
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TRANSPORTER -> INHIBITOR | |||
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ANHYDROUS->SOLVATE |
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IMPURITY -> PARENT |
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IMPURITY -> PARENT | |||
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IMPURITY -> PARENT |
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IMPURITY -> PARENT |
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ACTIVE MOIETY |
Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Biological Half-life | PHARMACOKINETIC |
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Volume of Distribution | PHARMACOKINETIC |
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