BOSENTAN

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 Search

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	C27H29N5O6S
Molecular Weight	551.614
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021290s012lbl.pdf | https://www.drugbank.ca/drugs/DB00559 | https://www.ncbi.nlm.nih.gov/pubmed/10353441

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	Potency
Endothelin receptor, ET-A/ET-B 3 Target ID: CHEMBL2096678 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021290s012lbl.pdf	Antagonist 2849
Endothelin receptor ET-A 22 Target ID: CHEMBL4566 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10353441 \| https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021290s012lbl.pdf	Antagonist 2849	4.7 nM [Ki]
Endothelin receptor ET-B 11 Target ID: CHEMBL1785 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10353441 \| https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021290s012lbl.pdf	Antagonist 2849	95.0 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pulmonary arterial hypertension 36 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/21290se8-001_tracleer_lbl.pdf	Primary		Approved 8583	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 2001

PubMed

Title	Date	PubMed
Bosentan (Tracleer) for pulmonary arterial hypertension.	2002-04-01	11941267
In vivo and in vitro studies exploring the pharmacokinetic interaction between bosentan, a dual endothelin receptor antagonist, and glyburide.	2002-04	11956508
Combined inhibition of neutral endopeptidase with angiotensin converting enzyme or endothelin converting enzyme in experimental diabetes.	2002-04	11910307
Treatment of primary pulmonary hypertension -- the next generation.	2002-03-21	11907295
Bosentan therapy for pulmonary arterial hypertension.	2002-03-21	11907289
Bosentan enters market with risk management program.	2002-03-15	11908242
[Bosentan in pulmonary hypertension].	2002-03	11925765
Chronic endothelin receptor blockade prevents renal vasoconstriction and sodium retention in rats with chronic heart failure.	2002-03	11922906
Influence of food intake and formulation on the pharmacokinetics and metabolism of bosentan, a dual endothelin receptor antagonist.	2002-03	11865964
Crosstalk of endothelin-1 and platelet-derived growth factor in cardiac allograft arteriosclerosis.	2002-02-20	11849873
Tracleer (bosentan).	2002-02-01	11821645
Tracleer. Tablets ease symptoms of rare lung disorder.	2002-02	11924160
Medical management of primary pulmonary hypertension.	2002-02	11829729
Endothelin antagonists and heart failure.	2002-02	11790297
[Physical endurance improves markedly. New therapy approach in pulmonary hypertension].	2002-01-17	11847889
[The effects of endothelin blockade on renal expression of angiotensin II type 1 receptor in diabetic hypertensive rats].	2002-01-10	11953118
Human endothelin subtype A receptor enhancement during tissue culture via de novo transcription.	2002-01	11844243
Direct left ventricular wall stretch activates GATA4 binding in perfused rat heart: involvement of autocrine/paracrine pathways.	2002-01	11810204
Endothelin is an important determinant of renal function in a rat model of acute liver and renal failure.	2002-01	11772977
Hyperhexosemia induced functional and structural changes in the kidneys: role of endothelins.	2002-01	11744810
Naftidrofuryl exerts antiserotonergic but no endothelin-receptor blocking effects in AS4.1 cells, juxtaglomerular cells and isolated perfused rat kidneys.	2002-01	11743222
Growth factors in idiopathic pulmonary fibrosis: relative roles.	2002	11806848
Endothelin-1, a regulator of angiogenesis in the chick chorioallantoic membrane.	2001-12-12	11740152
Coronary and aortic vasoreactivity protection with endothelin receptor antagonist, bosentan, after ischemia and hypoxia in aged rats.	2001-12-07	11740953
Endothelin blockade in angiotensin II hypertension: prevention and treatment studies in the rat.	2001-12	11903325
Small bowel review: diseases of the small intestine.	2001-12	11768246
Pulmonary hypertension associated with COPD.	2001-12	11737906
Angiotensin II activates collagen type I gene in the renal cortex and aorta of transgenic mice through interaction with endothelin and TGF-beta.	2001-12	11729239
Role of endogenous endothelin on coronary reflow after cardioplegic arrest.	2001-12	11726892
Endothelin antagonist reduces hemodynamic responses to vasopressin in DOCA-salt hypertension.	2001-12	11709418
Endothelin resets renal blood flow autoregulatory efficiency during acute blockade of NO in the rat.	2001-12	11704565
[Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomized placebo-controlled study].	2001-11	11826707
Rationale and perspective of endothelin-1 antagonism in acute heart failure.	2001-11	11811379
Effects of the endothelin receptor antagonist bosentan on cardiac performance during porcine endotoxin shock.	2001-11	11736680
Renal tubulointerstitial damage caused by persistent proteinuria is attenuated in AT1-deficient mice: role of endothelin-1.	2001-11	11696450
Endothelin-1 decreases glutamate uptake in primary cultured rat astrocytes.	2001-11	11600412
Endothelin receptor blockade in congestive heart failure.	2001-10-30	11684644
Potent and selective ET-A antagonists. 1. Syntheses and structure-activity relationships of N-(6-(2-(aryloxy)ethoxy)-4-pyrimidinyl)sulfonamide derivatives.	2001-10-11	11585441
Report from the 93rd Cardiovascular and Renal Drugs Advisory Committee Meeting, August 9-10, 2001.	2001-10-09	11591605
Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo-controlled study.	2001-10-06	11597664
Endothelin-receptor antagonists in pulmonary hypertension.	2001-10-06	11597660
Endothelin receptor blockade and nitric oxide bioactivity.	2001-10	11715916
Chronic blockade of endothelin receptors improves ischemia-induced angiogenesis in rat hindlimbs through activation of vascular endothelial growth factor-no pathway.	2001-10	11597932
Endothelin mediates phospholipase C stimulation in the proximal tubule during initiation of compensatory renal growth in adult rats.	2001-10	11593498
Endothelin involvement in respiratory centre activity.	2001-09	11728166
Ovarian hormones modulate endothelin-1 vascular reactivity and mRNA expression in DOCA-salt hypertensive rats.	2001-09	11566958
New pharmacological strategies for the treatment of heart failure.	2001-07	11757792
Influence of several methodological procedures utilized to obtain in vitro vascular preparations on endothelial activity.	2001	11824475
Current management of primary pulmonary hypertension.	2001	11708765
Pharmacological regulation of postischemic sinusoidal diameters in rats--a new approach for reducing hepatic ischemia/reperfusion injury.	2001	11564912

Patents

Sample Use Guides

In Vivo Use Guide

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

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 `Mon Mar 31 18:01:21 GMT 2025` Edited by `admin` on `Mon Mar 31 18:01:21 GMT 2025`
Record UNII	Q326023R30
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

BOSENTAN

Official Name

English

BOSENTAN MONOHYDRATE

Preferred 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 HYDRATE

Common Name

English

RO-47-0203/029

Code

English

Classification Tree Code System Code

NDF-RT

N0000175581