Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C27H29N5O6S |
| Molecular Weight | 551.6162 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CC(C)(C)c1ccc(cc1)S(=O)(=O)Nc2c(c(nc(-c3ncccn3)n2)OCCO)Oc4ccccc4OC
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)
| Molecular Formula | C27H29N5O6S |
| Molecular Weight | 551.6162 |
| 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 |
|---|---|---|---|
Target ID: CHEMBL2096678 |
|||
| 4.7 nM [Ki] | |||
| 95.0 nM [Ki] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| 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 |
|---|---|---|
| Endothelin antagonism with bosentan: a review of potential applications. | 1999 Apr |
|
| Bosentan reduces blood pressure and the target-organ damage induced by a high-fructose diet in rats. | 1999 Dec |
|
| Influence of several methodological procedures utilized to obtain in vitro vascular preparations on endothelial activity. | 2001 |
|
| Current management of primary pulmonary hypertension. | 2001 |
|
| 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 |
|
| The endothelin antagonist bosentan inhibits the canalicular bile salt export pump: a potential mechanism for hepatic adverse reactions. | 2001 Apr |
|
| Pharmacologic characterization of S-1255, a highly potent and orally active endothelin A receptor antagonist. | 2001 Apr |
|
| Improvement of respiratory function by bosentan during endotoxic shock in the pig. | 2001 Aug |
|
| Endothelin receptor blockade reduces ventricular dysfunction and injury after reoxygenation. | 2001 Aug |
|
| Endothelin blockade in angiotensin II hypertension: prevention and treatment studies in the rat. | 2001 Dec |
|
| Small bowel review: diseases of the small intestine. | 2001 Dec |
|
| Endothelin and heart failure. | 2001 Dec |
|
| Coronary and aortic vasoreactivity protection with endothelin receptor antagonist, bosentan, after ischemia and hypoxia in aged rats. | 2001 Dec 7 |
|
| Endothelin antagonism uncovers insulin-mediated vasorelaxation in vitro and in vivo. | 2001 Feb |
|
| Augmentation of endothelial function by endothelin antagonism in human saphenous vein conduits. | 2001 Feb |
|
| Endothelin synthesis and receptors in porcine kidney. | 2001 Jan |
|
| Endothelin receptor blockade improves endothelial function in human internal mammary arteries. | 2001 Jan |
|
| New pharmacological strategies for the treatment of heart failure. | 2001 Jul |
|
| Long-term endothelin receptor blockade improves cardiovascular function in diabetes. | 2001 Jul |
|
| Effects of the endothelin receptor antagonist Bosentan on ischaemia/reperfusion injury in rat skeletal muscle. | 2001 Jul 13 |
|
| Differential effects of angiotensin II versus endothelin-1 inhibitions in hypertrophic left ventricular myocardium during transition to heart failure. | 2001 Jul 31 |
|
| Aminoethyl-isothiourea inhibits the increase in plasma endothelin-1 caused by serogroup A streptococci and prolongs survival in rat peritoneal sepsis. | 2001 Jun |
|
| Subarachnoid haemorrhage-induced sympathoexcitation in rats is reversed by bosentan or sodium nitroprusside. | 2001 Mar |
|
| A new era in the treatment of primary pulmonary hypertension. | 2001 Mar |
|
| Endothelin receptor antagonists in congestive heart failure: a new therapeutic principle for the future? | 2001 May |
|
| Acute endothelin a receptor blockade in heart failure. | 2001 May 8 |
|
| Bosentan, an endothelin antagonist, augments hepatic graft function by reducing graft circulatory impairment following ischemia/reperfusion injury. | 2001 May-Jun |
|
| [Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomized placebo-controlled study]. | 2001 Nov |
|
| Rationale and perspective of endothelin-1 antagonism in acute heart failure. | 2001 Nov |
|
| Renal tubulointerstitial damage caused by persistent proteinuria is attenuated in AT1-deficient mice: role of endothelin-1. | 2001 Nov |
|
| Endothelin-1 decreases glutamate uptake in primary cultured rat astrocytes. | 2001 Nov |
|
| Endothelin mediates phospholipase C stimulation in the proximal tubule during initiation of compensatory renal growth in adult rats. | 2001 Oct |
|
| Endothelin-receptor antagonists in pulmonary hypertension. | 2001 Oct 6 |
|
| Ovarian hormones modulate endothelin-1 vascular reactivity and mRNA expression in DOCA-salt hypertensive rats. | 2001 Sep |
|
| In vivo and in vitro studies exploring the pharmacokinetic interaction between bosentan, a dual endothelin receptor antagonist, and glyburide. | 2002 Apr |
|
| Bosentan (Tracleer) for pulmonary arterial hypertension. | 2002 Apr 1 |
|
| Medical management of primary pulmonary hypertension. | 2002 Feb |
|
| Endothelin antagonists and heart failure. | 2002 Feb |
|
| Human endothelin subtype A receptor enhancement during tissue culture via de novo transcription. | 2002 Jan |
|
| Hyperhexosemia induced functional and structural changes in the kidneys: role of endothelins. | 2002 Jan |
|
| [The effects of endothelin blockade on renal expression of angiotensin II type 1 receptor in diabetic hypertensive rats]. | 2002 Jan 10 |
|
| Tracleer (bosentan). | 2002 Jan-Feb |
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
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
by
admin
on
Edited
Sat Jun 26 12:43:47 UTC 2021
by
admin
on
Sat Jun 26 12:43:47 UTC 2021
|
| Record UNII |
XUL93R30K2
|
| Record Status |
Validated (UNII)
|
| Record Version |
|
-
Download
| Name | Type | Language | ||
|---|---|---|---|---|
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Systematic Name | English |
| Classification Tree | Code System | Code | ||
|---|---|---|---|---|
|
NDF-RT |
N0000175581
Created by
admin on Sat Jun 26 12:43:48 UTC 2021 , Edited by admin on Sat Jun 26 12:43:48 UTC 2021
|
||
|
NDF-RT |
N0000175364
Created by
admin on Sat Jun 26 12:43:48 UTC 2021 , Edited by admin on Sat Jun 26 12:43:48 UTC 2021
|
||
|
WHO-ATC |
C02KX01
Created by
admin on Sat Jun 26 12:43:48 UTC 2021 , Edited by admin on Sat Jun 26 12:43:48 UTC 2021
|
| Code System | Code | Type | Description | ||
|---|---|---|---|---|---|
|
C81107
Created by
admin on Sat Jun 26 12:43:48 UTC 2021 , Edited by admin on Sat Jun 26 12:43:48 UTC 2021
|
PRIMARY | |||
|
147536-97-8
Created by
admin on Sat Jun 26 12:43:48 UTC 2021 , Edited by admin on Sat Jun 26 12:43:48 UTC 2021
|
PRIMARY | |||
|
M2625
Created by
admin on Sat Jun 26 12:43:48 UTC 2021 , Edited by admin on Sat Jun 26 12:43:48 UTC 2021
|
PRIMARY | Merck Index | ||
|
SUB05877MIG
Created by
admin on Sat Jun 26 12:43:48 UTC 2021 , Edited by admin on Sat Jun 26 12:43:48 UTC 2021
|
PRIMARY | |||
|
SUB25414
Created by
admin on Sat Jun 26 12:43:48 UTC 2021 , Edited by admin on Sat Jun 26 12:43:48 UTC 2021
|
PRIMARY | |||
|
147536-97-8
Created by
admin on Sat Jun 26 12:43:48 UTC 2021 , Edited by admin on Sat Jun 26 12:43:48 UTC 2021
|
PRIMARY | |||
|
DB00559
Created by
admin on Sat Jun 26 12:43:48 UTC 2021 , Edited by admin on Sat Jun 26 12:43:48 UTC 2021
|
PRIMARY | |||
|
XUL93R30K2
Created by
admin on Sat Jun 26 12:43:48 UTC 2021 , Edited by admin on Sat Jun 26 12:43:48 UTC 2021
|
PRIMARY | |||
|
1468845
Created by
admin on Sat Jun 26 12:43:48 UTC 2021 , Edited by admin on Sat Jun 26 12:43:48 UTC 2021
|
PRIMARY | RxNorm | ||
|
104865
Created by
admin on Sat Jun 26 12:43:48 UTC 2021 , Edited by admin on Sat Jun 26 12:43:48 UTC 2021
|
PRIMARY | |||
|
7195
Created by
admin on Sat Jun 26 12:43:48 UTC 2021 , Edited by admin on Sat Jun 26 12:43:48 UTC 2021
|
PRIMARY |
| Related Record | Type | Details | ||
|---|---|---|---|---|
|
EXCRETED UNCHANGED |
INTRAVENOUS ADMINISTRATION
AMOUNT EXCRETED
URINE
|
||
|
EXCRETED UNCHANGED |
ORAL ADMINISTRATION
AMOUNT EXCRETED
FECAL
|
||
|
METABOLIC ENZYME -> SUBSTRATE |
MAJOR
|
||
|
|
SALT/SOLVATE -> PARENT | |||
|
METABOLIC ENZYME -> SUBSTRATE |
MAJOR
|
||
|
BINDER->LIGAND |
BINDING
|
| Related Record | Type | Details | ||
|---|---|---|---|---|
|
|
ACTIVE MOIETY |
| Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
|---|---|---|---|---|---|---|
| Volume of Distribution | PHARMACOKINETIC |
|
|
|||
| Tmax | PHARMACOKINETIC |
|
ORAL ADMINISTRATION |
|
||
| Biological Half-life | PHARMACOKINETIC |
|
|
|||