BOSENTAN ANHYDROUS

Details

Stereochemistry	ACHIRAL
Molecular Formula	C27H29N5O6S
Molecular Weight	551.614
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=C(OC2=C(NS(=O)(=O)C3=CC=C(C=C3)C(C)(C)C)N=C(N=C2OCCO)C4=NC=CC=N4)C=CC=C1

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	551.614
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 2778
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 2778	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 2778	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 8429	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
Endothelin antagonism with bosentan: a review of potential applications.	1999 Apr	10353441
Adrenocorticotrophic hormone-induced hypertension in the rat: effects of the endothelin antagonist bosentan.	1999 Aug	10474778
Differential effects of the mixed ET(A)/ET(B)-receptor antagonist bosentan on endothelin-induced bronchoconstriction, vasoconstriction and prostacyclin release.	2000 Aug	10961375
Influence of several methodological procedures utilized to obtain in vitro vascular preparations on endothelial activity.	2001	11824475
The loop diuretic torasemide interferes with endothelin-1 actions in the aorta of hypertensive rats.	2001	11369815
Pulmonary hypertension associated with COPD.	2001 Dec	11737906
Role of endogenous endothelin on coronary reflow after cardioplegic arrest.	2001 Dec	11726892
Endothelin antagonist reduces hemodynamic responses to vasopressin in DOCA-salt hypertension.	2001 Dec	11709418
Endothelin resets renal blood flow autoregulatory efficiency during acute blockade of NO in the rat.	2001 Dec	11704565
Endothelin receptor antagonist prevents parathyroid cell proliferation of low calcium diet-induced hyperparathyroidism in rats.	2001 Jan	11145604
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
Endothelium-dependent relaxation in response to low concentrations of bradykinin is enhanced by phosphoramidon, bosentan and BQ-123 in bovine coronary arteries in vitro.	2001 Jun	11459133
Aminoethyl-isothiourea inhibits the increase in plasma endothelin-1 caused by serogroup A streptococci and prolongs survival in rat peritoneal sepsis.	2001 Jun	11386616
Update in pharmacologic treatment of hypertension.	2001 May	11407110
Endothelin receptor antagonists in congestive heart failure: a new therapeutic principle for the future?	2001 May	11345356
[Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomized placebo-controlled study].	2001 Nov	11826707
Rationale and perspective of endothelin-1 antagonism in acute heart failure.	2001 Nov	11811379
Renal tubulointerstitial damage caused by persistent proteinuria is attenuated in AT1-deficient mice: role of endothelin-1.	2001 Nov	11696450
Endothelin-1 decreases glutamate uptake in primary cultured rat astrocytes.	2001 Nov	11600412
Chronic blockade of endothelin receptors improves ischemia-induced angiogenesis in rat hindlimbs through activation of vascular endothelial growth factor-no pathway.	2001 Oct	11597932
In vivo and in vitro studies exploring the pharmacokinetic interaction between bosentan, a dual endothelin receptor antagonist, and glyburide.	2002 Apr	11956508
Bosentan (Tracleer) for pulmonary arterial hypertension.	2002 Apr 1	11941267
Tracleer. Tablets ease symptoms of rare lung disorder.	2002 Feb	11924160
Medical management of primary pulmonary hypertension.	2002 Feb	11829729
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
Tracleer (bosentan).	2002 Jan-Feb	11821645
[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

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 15 15:48:14 GMT 2023` Edited by `admin` on `Fri Dec 15 15:48:14 GMT 2023`
Record UNII	XUL93R30K2
Record Status	`Validated (UNII)`
Record Version

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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