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
Differential effects of the mixed ET(A)/ET(B)-receptor antagonist bosentan on endothelin-induced bronchoconstriction, vasoconstriction and prostacyclin release.	2000 Aug	10961375
Pharmacological regulation of postischemic sinusoidal diameters in rats--a new approach for reducing hepatic ischemia/reperfusion injury.	2001	11564912
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	11505783
Improvement of respiratory function by bosentan during endotoxic shock in the pig.	2001 Aug	11545627
Endothelin receptor blockade improves endothelial function in human internal mammary arteries.	2001 Jan	11121806
Long-term endothelin receptor blockade improves cardiovascular function in diabetes.	2001 Jul	11465653
Endothelin mediates some of the renal actions of acutely administered angiotensin II.	2001 Jul	11463769
Endothelin receptor antagonists in congestive heart failure: a new therapeutic principle for the future?	2001 May	11345356
Combined angiotensin and endothelin receptor blockade attenuates adverse cardiac remodeling post-myocardial infarction in the rat: possible role of transforming growth factor beta(1).	2001 May	11343419
Effects of the endothelin receptor antagonist bosentan on cardiac performance during porcine endotoxin shock.	2001 Nov	11736680
Endogenous endothelins mediate increased acidification in remnant kidneys.	2001 Sep	11518775
Growth factors in idiopathic pulmonary fibrosis: relative roles.	2002	11806848
In vivo and in vitro studies exploring the pharmacokinetic interaction between bosentan, a dual endothelin receptor antagonist, and glyburide.	2002 Apr	11956508
Combined inhibition of neutral endopeptidase with angiotensin converting enzyme or endothelin converting enzyme in experimental diabetes.	2002 Apr	11910307
Bosentan (Tracleer) for pulmonary arterial hypertension.	2002 Apr 1	11941267
Tracleer. Tablets ease symptoms of rare lung disorder.	2002 Feb	11924160
Direct left ventricular wall stretch activates GATA4 binding in perfused rat heart: involvement of autocrine/paracrine pathways.	2002 Jan	11810204
[The effects of endothelin blockade on renal expression of angiotensin II type 1 receptor in diabetic hypertensive rats].	2002 Jan 10	11953118
[Bosentan in pulmonary hypertension].	2002 Mar	11925765
Chronic endothelin receptor blockade prevents renal vasoconstriction and sodium retention in rats with chronic heart failure.	2002 Mar	11922906
Bosentan enters market with risk management program.	2002 Mar 15	11908242
Treatment of primary pulmonary hypertension -- the next generation.	2002 Mar 21	11907295
Bosentan therapy for pulmonary arterial hypertension.	2002 Mar 21	11907289

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

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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