CLAZOSENTAN

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C25H23N9O6S
Molecular Weight	577.572
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=C(OC2=C(OCCO)N=C(N=C2NS(=O)(=O)C3=CC=C(C)C=N3)C4=CC=NC(=C4)C5=NN=NN5)C=CC=C1

InChI

InChIKey=LFWCJABOXHSRGC-UHFFFAOYSA-N

InChI=1S/C25H23N9O6S/c1-15-7-8-20(27-14-15)41(36,37)32-24-21(40-19-6-4-3-5-18(19)38-2)25(39-12-11-35)29-22(28-24)16-9-10-26-17(13-16)23-30-33-34-31-23/h3-10,13-14,35H,11-12H2,1-2H3,(H,28,29,32)(H,30,31,33,34)

HIDE SMILES / InChI

Molecular Formula	C25H23N9O6S
Molecular Weight	577.572
Charge	0
Count

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

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21640651 | https://clinicaltrials.gov/ct2/show/NCT03585270 | https://www.ncbi.nlm.nih.gov/pubmed/9399983 | https://www.idorsia.com/about-idorsia/idorsia-today/our-pipeline

Clazosentan is an endothelin receptor antagonist, developed by the Swiss pharmaceutical company Actelion, and licensed to its spin-off, Idorsia. The drug was designed to inhibit endothelin-mediated cerebral vasospasm and associated delayed ischaemic neurological deficit. The drug has been investigated in a phase III clinical trials in patients with aneurysmal subarachnoid hemorrhage. Clazosentan at 5 mg/h had no significant effect on mortality and vasospasm-related morbidity or functional outcome. Clinical investigation of a higher dose of the drug is underway.

Approval Year

PubMed

Title	Date	PubMed
Preventing vasospasm improves outcome after aneurysmal subarachnoid hemorrhage: rationale and design of CONSCIOUS-2 and CONSCIOUS-3 trials.	2010-12	20838933
Patient age and vasospasm after subarachnoid hemorrhage.	2010-10	20881555
Impact of systemic inflammatory response syndrome on vasospasm, cerebral infarction, and outcome after subarachnoid hemorrhage: exploratory analysis of CONSCIOUS-1 database.	2010-10	20593247
Effect of endothelin-receptor antagonists on delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage remains unclear.	2009-12	19875735
Therapeutic approaches to cerebral vasospasm complicating ruptured aneurysm.	2009-11-16	21577350
Cortical spreading ischaemia is a novel process involved in ischaemic damage in patients with aneurysmal subarachnoid haemorrhage.	2009-07	19420089
Diagnosis and management of vasospasm.	2009-04-29	20948747
In vitro and in vivo pharmacokinetic characteristics of clazosentan, an intravenous endothelin receptor antagonist, in humans.	2009-03	19281726
Delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage: is angiographic vasospasm an epiphenomenon?	2009-02	19074477
Clazosentan, an endothelin receptor antagonist, prevents early hypoperfusion during the acute phase of massive experimental subarachnoid hemorrhage: a laser Doppler flowmetry study in rats.	2008-12	19035733
Clazosentan: an endothelin receptor antagonist for treatment of vasospasm after subarachnoid hemorrhage.	2008-11	18922111
Clazosentan to overcome neurological ischemia and infarction occurring after subarachnoid hemorrhage (CONSCIOUS-1): randomized, double-blind, placebo-controlled phase 2 dose-finding trial.	2008-11	18688013
IL-33 mediates antigen-induced cutaneous and articular hypernociception in mice.	2008-02-19	18250323
Vasospasm after aneurysmal subarachnoid hemorrhage: need for further study.	2008	19066110
[Systemic treatments of the vasospasm].	2007-11	17933488
Influence of ethnic origin and sex on the pharmacokinetics of clazosentan.	2007-11	17906281
Effect of delayed cerebral vasospasm on cerebrovascular endothelin A receptor expression and function.	2007-07	17639881
Cerebral vasospasm: looking beyond vasoconstriction.	2007-06	17466386
Cerebral vasospasm after subarachnoid hemorrhage: the emerging revolution.	2007-05	17479073
Tolerability, pharmacokinetics, and pharmacodynamics of clazosentan, a parenteral endothelin receptor antagonist.	2007-02	16636870
Effect of gender on the tolerability, safety and pharmacokinetics of clazosentan following long-term infusion.	2007	17914898
Clinical review: Prevention and therapy of vasospasm in subarachnoid hemorrhage.	2007	17705883
Effects of the selective endothelin A (ET(A)) receptor antagonist Clazosentan on cerebral perfusion and cerebral oxygenation following severe subarachnoid hemorrhage - preliminary results from a randomized clinical series.	2007	17700991
Profile of past and current clinical trials involving endothelin receptor antagonists: the novel "-sentan" class of drug.	2006-06	16740981
Endothelin receptor antagonists.	2006-06	16219361
Clazosentan (Actelion).	2006-03	16555688
Clazosentan (AXV-034343), a selective endothelin A receptor antagonist, in the prevention of cerebral vasospasm following severe aneurysmal subarachnoid hemorrhage: results of a randomized, double-blind, placebo-controlled, multicenter phase IIa study.	2005-07	16121967
Vasospasm.	2005-07	16121964
Cerebrovascular characterization of clazosentan, the first nonpeptide endothelin receptor antagonist shown to be clinically effective for the treatment of cerebral vasospasm. Part II: effect on endothelin(B) receptor-mediated relaxation.	2005-06	16028771
Cerebrovascular characterization of clazosentan, the first nonpeptide endothelin receptor antagonist clinically effective for the treatment of cerebral vasospasm. Part I: inhibitory effect on endothelin(A) receptor-mediated contraction.	2005-06	16028770
Effects of endothelin-1 and endothelin-1-receptor blockade on renal function in humans.	2004-11	15328386
Pathophysiological plasma ET-1 levels antagonize beta-adrenergic dilation of coronary resistance vessels in conscious dogs.	2004-10	15205173
Effects of endothelin-1 and endothelin-1 receptor blockade on cardiac output, aortic pressure, and pulse wave velocity in humans.	2003-06	12743011
Effect of Ro 61-1790, a selective endothelin-A receptor antagonist, on systemic and uterine hemodynamics and fetal oxygenation in sheep.	2002-01	11810085
Inhibition of endothelin-1 by the competitive ET(A) receptor antagonist Ro 61-1790 reduces lesion volume after cold injury in the rat.	2001-03	11316270

Patents

Substance Class	Chemical Created by `admin` on `Wed Apr 02 09:33:06 GMT 2025` Edited by `admin` on `Wed Apr 02 09:33:06 GMT 2025`
Record UNII	3DRR0X4728
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

AXV-034343

Preferred Name

English

CLAZOSENTAN

Official Name

English

RO-61-1790

Code

English

AXV-343434

Code

English

2-PYRIDINESULFONAMIDE, N-(6-(2-HYDROXYETHOXY)-5-(2-METHOXYPHENOXY)-2-(2-(1H-TETRAZOL-5-YL)-4-PYRIDINYL)-4-PYRIMIDINYL)-5-METHYL-

Systematic Name

English

Clazosentan [WHO-DD]

Common Name

English

RO 61-1790

Code

English

CLAZOSENTAN [USAN]

Common Name

English

clazosentan [INN]

Common Name

English

CLAZOSENTAN [MI]

Common Name

English

N-(6-(2-HYDROXYETHOXY)-5-(2-METHOXYPHENOXY)-2-(2-(1H-TETRAZOL-5-YL)PYRIDIN-4-YL)PYRIMIDIN-4-YL)-5-METHYLPYRIDINE-2-SULFONAMIDE

Systematic Name

English

VML-588

Code

English

ACT-108475

Code

English

Classification Tree Code System Code

FDA ORPHAN DRUG

217105