Clazosentan Sodium

Details

Stereochemistry	ACHIRAL
Molecular Formula	C25H21N9O6S.2Na
Molecular Weight	621.535
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[Na+].[Na+].COC1=C(OC2=C([N-]S(=O)(=O)C3=NC=C(C)C=C3)N=C(N=C2OCCO)C4=CC(=NC=C4)C5=NN=N[N-]5)C=CC=C1

InChI

InChIKey=PZNSONUYVNYXJZ-UHFFFAOYSA-N

InChI=1S/C25H21N9O6S.2Na/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;;/q-2;2*+1

HIDE SMILES / InChI

Molecular Formula	C25H22N9O6S
Molecular Weight	576.564
Charge	-1
Count

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

Molecular Formula	Na
Molecular Weight	22.9898
Charge	1
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
Effect of Ro 61-1790, a selective endothelin-A receptor antagonist, on systemic and uterine hemodynamics and fetal oxygenation in sheep.	2002 Jan	11810085
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 clinically effective for the treatment of cerebral vasospasm. Part I: inhibitory effect on endothelin(A) receptor-mediated contraction.	2005 Jun	16028770
Clazosentan (Actelion).	2006 Mar	16555688
Effect of gender on the tolerability, safety and pharmacokinetics of clazosentan following long-term infusion.	2007	17914898
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
Effect of delayed cerebral vasospasm on cerebrovascular endothelin A receptor expression and function.	2007 Jul	17639881
Cerebral vasospasm after subarachnoid hemorrhage: the emerging revolution.	2007 May	17479073
[Systemic treatments of the vasospasm].	2007 Nov	17933488
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
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 `Fri Dec 15 16:37:20 GMT 2023` Edited by `admin` on `Fri Dec 15 16:37:20 GMT 2023`
Record UNII	0L77PK62L1
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

Clazosentan Sodium

Official Name

English

CLAZOSENTAN SODIUM [USAN]

Common Name

English

Clazosentan sodium [WHO-DD]

Common Name

English

CLAZOSENTAN SODIUM [JAN]

Common Name

English

CLAZOSENTAN DISODIUM SALT

Common Name

English

Disodium N-{2-[2-(1H-tetrazol-5-yl)pyridin-4-yl]-6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)pyrimidin-4-yl}-5-methylpyridine-2-sulfonamide

Systematic Name

English

CLAZOSENTAN DISODIUM SALT [MI]

Common Name

English

2-Pyridinesulfonamide, N-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-[2-(1Htetrazol-5-yl)-4-pyridinyl]-4-pyrimidinyl]-5-(1-methyl)-, disodium salt (1:2)

Common Name

English

ACT-108475A

Code

English

Classification Tree Code System Code

EU-Orphan Drug

EU/3/03/182