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	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

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 2737
Endothelin receptor ET-A 19 Target ID: CHEMBL4566 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10353441 \| https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021290s012lbl.pdf	Antagonist 2737	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 2737	95.0 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pulmonary arterial hypertension 35 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/21290se8-001_tracleer_lbl.pdf	Primary		Approved 8307	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

Title	Date	PubMed
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
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
The loop diuretic torasemide interferes with endothelin-1 actions in the aorta of hypertensive rats.	2001	11369815
Activation of NF-kappaB in tubular epithelial cells of rats with intense proteinuria: role of angiotensin II and endothelin-1.	2001 Apr	11304520
Pharmacologic characterization of S-1255, a highly potent and orally active endothelin A receptor antagonist.	2001 Apr	11300660
Endothelin antagonist reduces hemodynamic responses to vasopressin in DOCA-salt hypertension.	2001 Dec	11709418
Therapeutic role of bosentan in hypertension: lessons from the model of perinephritic hypertension.	2001 Dec	11447300
Regression of renal vascular fibrosis by endothelin receptor antagonism.	2001 Feb	11230324
Augmentation of endothelial function by endothelin antagonism in human saphenous vein conduits.	2001 Feb	11213966
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	11444506
Neurogenic inflammation in the context of migraine.	2001 May 1	11301492
Bosentan, an endothelin antagonist, augments hepatic graft function by reducing graft circulatory impairment following ischemia/reperfusion injury.	2001 May-Jun	11360057
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	11585441
Endothelin receptor blockade in congestive heart failure.	2001 Oct 30	11684644
Report from the 93rd Cardiovascular and Renal Drugs Advisory Committee Meeting, August 9-10, 2001.	2001 Oct 9	11591605
Ovarian hormones modulate endothelin-1 vascular reactivity and mRNA expression in DOCA-salt hypertensive rats.	2001 Sep	11566958
Growth factors in idiopathic pulmonary fibrosis: relative roles.	2002	11806848
Hyperhexosemia induced functional and structural changes in the kidneys: role of endothelins.	2002 Jan	11744810
[Physical endurance improves markedly. New therapy approach in pulmonary hypertension].	2002 Jan 17	11847889
Tracleer (bosentan).	2002 Jan-Feb	11821645
Influence of food intake and formulation on the pharmacokinetics and metabolism of bosentan, a dual endothelin receptor antagonist.	2002 Mar	11865964

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 `Fri Dec 16 17:27:53 UTC 2022` Edited by `admin` on `Fri Dec 16 17:27:53 UTC 2022`
Record UNII	Q326023R30
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

BOSENTAN

Official 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 MONOHYDRATE

Common Name

English

BOSENTAN HYDRATE

Common Name

English

RO-47-0203/029

Code

English

Classification Tree Code System Code

NDF-RT

N0000175581