CLAZOSENTAN

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=CC=CC=C1OC2=C(OCCO)N=C(N=C2NS(=O)(=O)C3=NC=C(C)C=C3)C4=CC=NC(=C4)C5=NN=NN5

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
Inhibition of endothelin-1 by the competitive ET(A) receptor antagonist Ro 61-1790 reduces lesion volume after cold injury in the rat.	2001 Mar	11316270
Effects of endothelin-1 and endothelin-1-receptor blockade on renal function in humans.	2004 Nov	15328386
Pathophysiological plasma ET-1 levels antagonize beta-adrenergic dilation of coronary resistance vessels in conscious dogs.	2004 Oct	15205173
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 Jul	16121967
Vasospasm.	2005 Jul	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 Jun	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 Jun	16028770
Profile of past and current clinical trials involving endothelin receptor antagonists: the novel "-sentan" class of drug.	2006 Jun	16740981
Endothelin receptor antagonists.	2006 Jun	16219361
Clazosentan (Actelion).	2006 Mar	16555688
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
Tolerability, pharmacokinetics, and pharmacodynamics of clazosentan, a parenteral endothelin receptor antagonist.	2007 Feb	16636870
Effect of delayed cerebral vasospasm on cerebrovascular endothelin A receptor expression and function.	2007 Jul	17639881
Cerebral vasospasm: looking beyond vasoconstriction.	2007 Jun	17466386
Cerebral vasospasm after subarachnoid hemorrhage: the emerging revolution.	2007 May	17479073
[Systemic treatments of the vasospasm].	2007 Nov	17933488
Influence of ethnic origin and sex on the pharmacokinetics of clazosentan.	2007 Nov	17906281
Vasospasm after aneurysmal subarachnoid hemorrhage: need for further study.	2008	19066110
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 Dec	19035733
IL-33 mediates antigen-induced cutaneous and articular hypernociception in mice.	2008 Feb 19	18250323
Clazosentan: an endothelin receptor antagonist for treatment of vasospasm after subarachnoid hemorrhage.	2008 Nov	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 Nov	18688013
Diagnosis and management of vasospasm.	2009 Apr 29	20948747
Effect of endothelin-receptor antagonists on delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage remains unclear.	2009 Dec	19875735
Delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage: is angiographic vasospasm an epiphenomenon?	2009 Feb	19074477
Cortical spreading ischaemia is a novel process involved in ischaemic damage in patients with aneurysmal subarachnoid haemorrhage.	2009 Jul	19420089
In vitro and in vivo pharmacokinetic characteristics of clazosentan, an intravenous endothelin receptor antagonist, in humans.	2009 Mar	19281726
Therapeutic approaches to cerebral vasospasm complicating ruptured aneurysm.	2009 Nov 16	21577350
Preventing vasospasm improves outcome after aneurysmal subarachnoid hemorrhage: rationale and design of CONSCIOUS-2 and CONSCIOUS-3 trials.	2010 Dec	20838933
Patient age and vasospasm after subarachnoid hemorrhage.	2010 Oct	20881555
Impact of systemic inflammatory response syndrome on vasospasm, cerebral infarction, and outcome after subarachnoid hemorrhage: exploratory analysis of CONSCIOUS-1 database.	2010 Oct	20593247

Patents

Substance Class	Chemical Created by `admin` on `Sat Dec 16 17:48:25 UTC 2023` Edited by `admin` on `Sat Dec 16 17:48:25 UTC 2023`
Record UNII	3DRR0X4728
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

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

AXV-034343

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