SITAXENTAN

Details

Stereochemistry	ACHIRAL
Molecular Formula	C18H15ClN2O6S2
Molecular Weight	454.9073
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cc1cc2c(cc1CC(=O)c3c(ccs3)S(=O)(=O)Nc4c(c(C)no4)Cl)OCO2

InChI

InChIKey=PHWXUGHIIBDVKD-UHFFFAOYSA-N

InChI=1S/C18H15ClN2O6S2/c1-9-5-13-14(26-8-25-13)7-11(9)6-12(22)17-15(3-4-28-17)29(23,24)21-18-16(19)10(2)20-27-18/h3-5,7,21H,6,8H2,1-2H3

HIDE SMILES / InChI

Molecular Formula	C18H15ClN2O6S2
Molecular Weight	454.9073
Charge	0
Count

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

Description
Sources: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000679/WC500037902.pdf
Curator's Comment:: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/9171878 | http://adisinsight.springer.com/drugs/800007312 | http://www.pfizer.com/news/press-release/press-release-detail/pfizer_stops_clinical_trials_of_thelin_and_initiates_voluntary_product_withdrawal_in_the_interest_of_patient_safety

Sitaxentan (TBC11251, trade name Thelin) is a potent and selective Endothelin A receptor antagonist. Sitaxentan was under development by Encysive Pharmaceuticals (now Pfizer) for use in the treatment of pulmonary hypertension, congestive heart failure and asthma. It was launched in the major markets of the European Union (EU) under name Thelin for the treatment of pulmonary arterial hypertension. In December 2010, Pfizer discontinued clinical trials of sitaxentan worldwide and initiated voluntary product withdrawal from markets where it is approved due to life-threatening idiosyncratic risk of liver injury.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Endothelin receptor ET-A 19 Target ID: CHEMBL252 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9171878/	Antagonist 2575		0.43 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Pulmonary arterial hypertension 34 Sources: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000679/WC500037902.pdf	Primary	Withdrawn	THELIN Approved Use Treatment of patients with pulmonary arterial hypertension (PAH) classified as WHO functional class III, to improve exercise capacity. Efficacy has been shown in primary pulmonary hypertension and in pulmonary hypertension associated with connective tissue disease. Launch Date 1.16017922E12
Heart failure 83 Sources: http://adisinsight.springer.com/drugs/800007312	Primary	Phase II 1101	THELIN Approved Use Treatment of patients with pulmonary arterial hypertension (PAH) classified as WHO functional class III, to improve exercise capacity. Efficacy has been shown in primary pulmonary hypertension and in pulmonary hypertension associated with connective tissue disease. Launch Date 1.16017922E12
Asthma 227 Sources: http://adisinsight.springer.com/drugs/800007312	Primary	Phase II 1101	THELIN Approved Use Treatment of patients with pulmonary arterial hypertension (PAH) classified as WHO functional class III, to improve exercise capacity. Efficacy has been shown in primary pulmonary hypertension and in pulmonary hypertension associated with connective tissue disease. Launch Date 1.16017922E12

PubMed

Title	Date	PubMed
Discovery of TBC11251, a potent, long acting, orally active endothelin receptor-A selective antagonist.	1997 May 23	9171878
High glucose-induced, endothelin-dependent fibronectin synthesis is mediated via NF-kappa B and AP-1.	2003 Feb	12388107
Clinical trials and basic research: defining mechanisms and improving treatment in connective tissue disease.	2007	17767739
Inhibition of endothelin receptors in the treatment of pulmonary arterial hypertension: does selectivity matter?	2008 Aug	18562303
Sitaxentan: new drug. Pulmonary hypertension: better to continue to use bosentan.	2008 Jun	18630348
[Systemic sclerosis].	2008 May	18552072
[Specific drugs for the treatment of pulmonary arterial hypertension - current status].	2008 Oct	18814092
Pulmonary arterial hypertension: on the way to a manageable disease.	2008 Sep	18729002
Cost-utility of treatments for pulmonary arterial hypertension: a Markov state-transition decision analysis model.	2009	19715380
Bosentan in the treatment of pulmonary arterial hypertension with the focus on the mildly symptomatic patient.	2009	19688101
[Endothelin receptor antagonists - their role in pulmonary medicine].	2009 Dec	20032843
Integrated care and optimal management of pulmonary arterial hypertension.	2009 May 12	21197349
Early intervention in pulmonary arterial hypertension associated with systemic sclerosis: an essential component of disease management.	2010 Dec	21119190
Long term combination treatment for severe idiopathic pulmonary arterial hypertension.	2010 Mar 26	21160759
The emergence of oral tadalafil as a once-daily treatment for pulmonary arterial hypertension.	2010 May 6	20479949

Patents

Sample Use Guides

In Vivo Use Guide

Thelin is to be taken orally as a dose of 100 mg once daily.

Route of Administration: Oral

In Vitro Use Guide

Unknown

Substance Class	Chemical Created by `admin` on `Fri Jun 25 21:31:40 UTC 2021` Edited by `admin` on `Fri Jun 25 21:31:40 UTC 2021`
Record UNII	J9QH779MEM
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

SITAXENTAN

Official Name

English

IPI-1040

Code

English

SITAXENTAN [WHO-DD]

Common Name

English

SITAXENTAN [INN]

Common Name

English

SITAXSENTAN

Common Name

English

SITAXENTAN [USAN]

Common Name

English

TBC-11251

Code

English

N-(4-CHLORO-3-METHYL-5-ISOXAZOLYL)-2-(3,4-(METHYLENEDIOXY)-6-METHYL)PHENYLACETYL-3-THIOPHENESULFONAMIDE

Common Name

English

N-(4-CHLORO-3-METHYL-5-ISOXAZOLYL)-2-((4,5-(METHYLENEDIOXY)-O-TOLY)ACETYL)-3-THIOPHENESULFONAMIDE

Common Name

English

SITAXSENTAN [MI]

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

793420