Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C27H27N9O6S |
| Molecular Weight | 605.625 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
COC1=CC=CC=C1OC2=C(OCCO)N=C(N=C2NS(=O)(=O)C3=NC=C(C=C3)C(C)C)C4=CC(=NC=C4)C5=NN=NN5
InChI
InChIKey=TUYWTLTWNJOZNY-UHFFFAOYSA-N
InChI=1S/C27H27N9O6S/c1-16(2)18-8-9-22(29-15-18)43(38,39)34-26-23(42-21-7-5-4-6-20(21)40-3)27(41-13-12-37)31-24(30-26)17-10-11-28-19(14-17)25-32-35-36-33-25/h4-11,14-16,37H,12-13H2,1-3H3,(H,30,31,34)(H,32,33,35,36)
| Molecular Formula | C27H27N9O6S |
| Molecular Weight | 605.625 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
DescriptionCurator's Comment: The description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/15055997 | https://clinicaltrials.gov/ct2/show/NCT00524433 | https://www.ncbi.nlm.nih.gov/pubmed/14632537 | https://clinicaltrials.gov/ct2/show/NCT01077297 | https://www.ncbi.nlm.nih.gov/pubmed/22474738
Curator's Comment: The description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/15055997 | https://clinicaltrials.gov/ct2/show/NCT00524433 | https://www.ncbi.nlm.nih.gov/pubmed/14632537 | https://clinicaltrials.gov/ct2/show/NCT01077297 | https://www.ncbi.nlm.nih.gov/pubmed/22474738
Tezosentan (Veletri; Ro 61–0612) is a dual endothelin receptor antagonist that has been shown to improve cardiac output, decrease pulmonary capillary wedge pressure, and reduce pulmonary and systemic vascular resistance in initial clinical studies in acutely decompensated heart failure. Tezosentan is a water-soluble ET-1 receptor antagonist with high affinity to both ETA and ETB receptors but greater potency for the ETA receptor subtype. Clinical studies demonstrated mixed results for Tezosentan regarding its efficacy and tolerability in the management of decompensated heart failure. The side effects of Tezosentan include a headache, nausea, and hypotension.
Approval Year
PubMed
| Title | Date | PubMed |
|---|---|---|
| The development of new medical treatments for acute decompensated heart failure. | 2002 |
|
| The effect of tezosentan, a non-selective endothelin receptor antagonist, on shear stress-induced changes in arterial diameter of the anaesthetized dog. | 2002 Nov 1 |
|
| Tezosentan in patients with acute heart failure and acute coronary syndromes: design of the Randomized Intravenous Tezosentan study (RITZ-4). | 2002 Oct |
|
| Endothelins induce gallbladder contraction independent of elevated blood pressure in vivo in the Australian possum. | 2002 Sep-Oct |
|
| [Endothelin receptor blockers--one more agent for the treatment of pulmonary hypertension]. | 2003 |
|
| In vivo and in vitro disposition profile of tezosentan, an intravenous dual endothelin receptor antagonist, in humans. | 2003 Apr |
|
| Clinical trials update from the European Society of Cardiology Heart Failure meeting: COMET, COMPANION, Tezosentan and SHAPE. | 2003 Aug |
|
| Tezosentan in the treatment of acute heart failure. | 2003 Dec |
|
| Haemodynamic effects of endothelin receptor antagonist, tezosentan, in tumour necrosis factor-alpha treated anaesthetized rats. | 2003 Feb |
|
| Tezosentan in patients with acute heart failure and acute coronary syndromes: design of the fourth Randomized Intravenous Tezosentan Study (RITZ-4). | 2003 Feb |
|
| Dyspnea as an end point in clinical trials of therapies for acute decompensated heart failure. | 2003 Feb |
|
| RITZ-5: randomized intravenous TeZosentan (an endothelin-A/B antagonist) for the treatment of pulmonary edema: a prospective, multicenter, double-blind, placebo-controlled study. | 2003 Jan 15 |
|
| ETA and ETB receptor function in pancreatitis-associated microcirculatory failure, inflammation, and parenchymal injury. | 2003 Jul |
|
| Hemodynamic and clinical effects of tezosentan, an intravenous dual endothelin receptor antagonist, in patients hospitalized for acute decompensated heart failure. | 2003 Jul 2 |
|
| Determination of tezosentan, a parenteral endothelin receptor antagonist, in human plasma by liquid chromatography-tandem mass spectrometry. | 2003 Jul 25 |
|
| Effect of severe renal impairment on the pharmacokinetics and tolerability of the parenteral endothelin antagonist tezosentan. | 2003 Jun |
|
| Current status of endothelin blockade for the treatment of cardiovascular and pulmonary vascular disease. | 2003 Mar |
|
| Tezosentan. Actelion/Genentech. | 2003 Mar |
|
| Will endothelin receptor antagonists have a role in heart failure? | 2003 Mar |
|
| The neurohormonal paradigm: have we gone too far? | 2003 May 7 |
|
| Tezosentan in patients with acute heart failure and acute coronary syndromes: results of the Randomized Intravenous TeZosentan Study (RITZ-4). | 2003 May 7 |
|
| New and emerging drug therapies for the management of acute heart failure. | 2003 Nov |
|
| Effects of the endothelin-1 receptor antagonist tezosentan on renal blood flow and diuresis during prolonged increased intra-abdominal pressure. | 2003 Nov |
|
| Endothelin in neurohormonal activation in heart failure. | 2003 Nov |
|
| Contribution of endothelin and its receptors to the regulation of vascular tone during exercise is different in the systemic, coronary and pulmonary circulation. | 2003 Sep 1 |
|
| Tezosentan, an endothelin receptor antagonist, limits liver injury in endotoxin challenged cirrhotic rats. | 2004 Dec |
|
| Endogenous endothelin increases gallbladder tone and leads to acute cholecystitis in the Australian possum. | 2004 Feb |
|
| Role of endothelin-1 and thromboxane A2 in the pulmonary hypertension induced by heparin-protamine interaction in anesthetized dogs. | 2004 Jan |
|
| Comparison of the role of endothelin, vasopressin and angiotensin in arterial pressure regulation during sevoflurane anaesthesia in dogs. | 2004 Jan |
|
| Acute cardiopulmonary effects of a dual-endothelin receptor antagonist on oleic acid-induced pulmonary arterial hypertension in dogs. | 2004 Jan-Feb |
|
| Usefulness of an elevated troponin-I in predicting clinical events in patients admitted with acute heart failure and acute coronary syndrome (from the RITZ-4 trial). | 2004 Jun 1 |
|
| Novel endothelin receptor antagonist attenuates endotoxin-induced lung injury in sheep. | 2004 Mar |
|
| Nitric oxide synthase inhibition and elevated endothelin increase oxygen consumption but do not affect glucose and palmitate oxidation in the isolated rat heart. | 2004 Mar |
|
| Influence of mild liver impairment on the pharmacokinetics of tezosentan, a drug excreted unchanged into bile. | 2004 Mar |
|
| Contribution of endothelin to coronary vasomotor tone is abolished after myocardial infarction. | 2005 Feb |
|
| Medical and ventilatory treatment of acute heart failure: new insights. | 2006 |
|
| Effects of endothelin antagonist tezosentan on orthodontic tooth movement in rats. | 2006 Apr |
|
| Comparison of the pharmacokinetics, pharmacodynamics and tolerability of tezosentan between caucasian and Japanese subjects. | 2006 Apr |
|
| Endothelin-2 in ovarian follicle rupture. | 2006 Apr |
|
| Newer approaches to the pharmacological management of heart failure. | 2006 Feb |
|
| Tezosentan decreases pulmonary artery pressure and improves survival rate in an animal model of meconium aspiration. | 2006 Jan |
|
| Nebulized therapies for childhood pulmonary hypertension: an in vitro model. | 2006 Jul |
|
| Role of endothelin receptor activation in secondary pulmonary hypertension in awake swine after myocardial infarction. | 2006 Jul 15 |
|
| Effects of endothelin receptor antagonism on acute lung injury induced by chlorine gas. | 2006 Jun |
|
| Endothelin receptor antagonists. | 2006 Jun |
|
| The role of indomethacin and tezosentan on renal effects induced by Bothrops moojeni Lys49 myotoxin I. | 2006 Jun 15 |
|
| Optimizing outcomes in the patient with acute decompensated heart failure. | 2006 Mar |
|
| The role of endothelin-1 in hyperoxia-induced lung injury in mice. | 2006 Mar 27 |
|
| [Medical and ventilatory treatment of acute heart failure]. | 2006 Mar 9 |
|
| Nitric oxide-endothelin-1 interactions after surgically induced acute increases in pulmonary blood flow in intact lambs. | 2006 May |
Patents
Sample Use Guides
single infusion of tezosentan 5mg/h over 30 min corresponding to 2.5 mg
Route of Administration:
Intravenous
Aortic valves were obtained from 16 patients at the time of aortic valve replacement surgery. After surgical removal, each valve was divided approximately into 15 pieces. Valve pieces (4 mm diameter) of normal and sclerotic aortic valves were cultured in αMEM (Gibco, Paisley, UK), supplemented with 10% heat-inactivated fetal bovine serum (FBS; Autogen Bioclear, Wiltshire, UK), 20 mM HEPES (Gibco) 100 U/ml penicillin, 0.1 mg/ml streptomycin (Gibco) and 2 mM L-glutamine (Gibco) at 37°C in 5% CO2 and 95% air. For the measurement of radioactivity in cell culture experiments, valve pieces from two normal patients (resulting in 30 valve pieces) as well as six stenotic patients (resulting in 90 valve pieces) were inserted into the 24-well plates, the medium was changed, and the test drugs (125I-ET-1, 10 nmol/l; ET-1, 100 µmol/l; tezosentan, 10 nmol/l) were added on the second day of culture. After 20 min and 3 h of incubation, the valves were washed three times with DPBS (BioWhittaker, Lonza, Belgium). Radioactivity was measured using a Wallac Multigamma counter (Wallac, Turku, Finland) and results were expressed as counts per minute.
| Substance Class |
Chemical
Created
by
admin
on
Edited
Wed Apr 02 08:44:41 GMT 2025
by
admin
on
Wed Apr 02 08:44:41 GMT 2025
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| Record UNII |
64J9J55263
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| Record Status |
Validated (UNII)
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| Record Version |
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Tezosentan
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