SIBENADET

Details

Stereochemistry	ACHIRAL
Molecular Formula	C22H28N2O5S2
Molecular Weight	464.598
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC1=C2NC(=O)SC2=C(CCNCCS(=O)(=O)CCCOCCC3=CC=CC=C3)C=C1

InChI

InChIKey=DBCKRBGYGMVSTI-UHFFFAOYSA-N

InChI=1S/C22H28N2O5S2/c25-19-8-7-18(21-20(19)24-22(26)30-21)9-11-23-12-16-31(27,28)15-4-13-29-14-10-17-5-2-1-3-6-17/h1-3,5-8,23,25H,4,9-16H2,(H,24,26)

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Description
Sources: https://adisinsight.springer.com/drugs/800009719 | https://www.ncbi.nlm.nih.gov/pubmed/12564607

AstraZeneca R&D Charnwood (formerly Astra Charnwood, a subsidiary of AstraZeneca) was developing sibenadet (Viozan, AR-C68397AA) for the potential treatment of chronic obstructive pulmonary disease and asthma. Sibenadet is a dual D2 dopamine receptor, beta2-adrenoceptor agonist that combines bronchodilator activity with the sensory afferent modulating effects associated with D2-receptor agonism. Development of sibenadet has been discontinued due to disappointing efficacy findings.

Originator

Approval Year

PubMed

Title	Date	PubMed
Inhibition by viozan of extravasation induced in rat trachea by capsaicin is mediated exclusively by beta 2-adrenoceptors.	2001 Dec	11770013
Dynamic modelling of a challenge-escalation cross-over study of treatment of capsaicin-induced coughing.	2002 Oct 30	12369079
Conclusion. Lessons from the novel D2 dopamine receptor, beta2-adrenoceptor agonist, Viozan: chronic obstructive pulmonary disease and drug development implications.	2003 Jan	12564613
Evaluating symptoms in chronic obstructive pulmonary disease: validation of the Breathlessness, Cough and Sputum Scale.	2003 Jan	12564612
Utilization of health care services by patients with chronic obstructive pulmonary disease.	2003 Jan	12564611
Long-term use of Viozan (sibenadet HCl) in patients with chronic obstructive pulmonary disease: results of a 1-year study.	2003 Jan	12564610
Symptoms are an important outcome in chronic obstructive pulmonary disease clinical trials: results of a 3-month comparative study using the Breathlessness, Cough and Sputum Scale (BCSS).	2003 Jan	12564609
The role of the novel D2/beta2-agonist, Viozan (sibenadet HCl), in the treatment of symptoms of chronic obstructive pulmonary disease: results of a large-scale clinical investigation.	2003 Jan	12564608
Early clinical investigation of Viozan (sibenadet HCl), a novel D2 dopamine receptor, beta2-adrenoceptor agonist for the treatment of chronic obstructive pulmonary disease symptoms.	2003 Jan	12564607
Dual dopamine D2 receptor and beta2-adrenoceptor agonists for the treatment of chronic obstructive pulmonary disease: the pre-clinical rationale.	2003 Jan	12564606
Introduction. The symposium that never occurred: pre-clinical and clinical development of sibenadet.	2003 Jan	12564605
Suppression of histamine-induced tachypnoea in the rhesus monkey by sibenadet: no role for dopamine D2 receptors.	2004 Jan	15307823
Multivariate estimation of the relative dose potency.	2004 Jul 30	15236424
Mucociliary clearance in COPD can be increased by both a D2/beta2 and a standard beta2 agonists.	2005 Feb	15715181
Understanding the polymorphic behavior of sibenadet hydrochloride through detailed studies integrating structural and dynamical assessment.	2005 Nov	16200581
Lack of correlation between exercise and sibenadet-induced changes in heart rate corrected measurement of the QT interval.	2007 Mar	17380588

Patents

Sample Use Guides

In Vivo Use Guide

701 patients were randomized to one of three sibenadet dose groups (400, 600 or 1000 ug ex valve), salbutamol 200 ug, ipratropium bromide (IB) 40 ug or placebo, all three times daily via pressurized metered dose inhaler (pMDI) for 4 weeks. Once the results of Study 1 had been evaluated, a dose-ranging, study (Study 2) involving 872 patients randomized to receive sibenadet (45, 270, or 495 ug ex actuator), or placebo all three times daily via pMDI, for 6 weeks commenced.

Route of Administration: Respiratory

In Vitro Use Guide

Sibenadet is a weak R1-adrenoceptor agonist (R1(REA): p[A]50 6.08, IA 0.08). It is a dual D2-receptor agonist (D2(REA): p[A]50 8.94, IA 0.90; essentially a full agonist at the D2-receptor) and beta2-adrenoceptor partial agonist (beta2(GPT): p[A]50 7.95

Name

Type

Language

SIBENADET

Official Name

English

4-HYDROXY-7-(2-((2-((3-(2-PHENYLETHOXY)PROPYL)SULFONYL)ETHYL)AMINO)ETHYL)-1,3-BENZOTHIAZOL-2(3H)-ONE

Systematic Name

English

2(3H)-BENZOTHIAZOLONE, 4-HYDROXY-7-(2-((2-((3-(2-PHENYLETHOXY)PROPYL)SULFONYL)ETHYL)AMINO)ETHYL)-

Systematic Name

English

sibenadet [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C48149