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 |
|---|---|---|
| Tezosentan (an intravenous endothelin receptor A/B antagonist) reduces peripheral resistance and increases cardiac power therefore preventing a steep decrease in blood pressure in patients with congestive heart failure. | 2001 Aug |
|
| Endothelin-1 blockade corrects mesenteric hypoperfusion in a porcine low cardiac output model. | 2001 Aug |
|
| A pilot safety trial of prolonged (48 h) infusion of the dual endothelin-receptor antagonist tezosentan in patients with advanced heart failure. | 2001 Aug |
|
| Endothelin mediates the altered renal hemodynamics associated with experimental congestive heart failure. | 2001 Aug |
|
| The dual endothelin receptor antagonist tezosentan acutely improves hemodynamic parameters in patients with advanced heart failure. | 2001 Aug |
|
| Clinical trials update: highlights of the scientific sessions of the XXIII Congress of the European Society of Cardiology--WARIS II, ESCAMI, PAFAC, RITZ-1 and TIME. | 2001 Dec |
|
| Effects of tezosentan, a dual endothelin receptor antagonist, on the cardiovascular and renal systems of neonatal piglets. | 2001 Dec |
|
| Role of endogenous endothelin on coronary reflow after cardioplegic arrest. | 2001 Dec |
|
| Endogenous endothelin and vasopressin support blood pressure during epidural anesthesia in conscious dogs. | 2001 Dec |
|
| Endothelin receptor blockade improves oxygenation in contralateral TRAM flap tissue in pigs. | 2001 Jul |
|
| Additional effects of endothelin receptor blockade and angiotensin converting enzyme inhibition in rats with chronic heart failure. | 2001 Jun |
|
| Clinical Trials Update: CAPRICORN, COPERNICUS, MIRACLE, STAF, RITZ-2, RECOVER and RENAISSANCE and cachexia and cholesterol in heart failure. Highlights of the Scientific Sessions of the American College of Cardiology, 2001. | 2001 Jun |
|
| Endothelin-1 induces contraction of human and Australian possum gallbladder in vitro. | 2001 Oct 15 |
|
| Endothelin receptor blockade in congestive heart failure. | 2001 Oct 30 |
|
| The development of new medical treatments for acute decompensated heart failure. | 2002 |
|
| Tezosentan inhibits both equinatoxin II and endotelin-1 induced contractions of isolated porcine coronary artery in a similar way. | 2002 Aug |
|
| Short-term endothelin receptor blockade with tezosentan has both immediate and long-term beneficial effects in rats with myocardial infarction. | 2002 Jan 2 |
|
| Endothelin in the mechanism of endothelial injury and neutrophil adhesion in the post-ischemic guinea-pig heart. | 2002 Jan 2 |
|
| [Treatment of heart failure: an update]. | 2002 Jul |
|
| Cyclosporin increases the exposure to tezosentan, an intravenous dual endothelin receptor antagonist. | 2002 Jul |
|
| Entry-into-humans study with tezosentan, an intravenous dual endothelin receptor antagonist. | 2002 Jun |
|
| Endothelin-3 induces both human and opossum gallbladder contraction mediated mainly by endothelin-B receptor subtype in vitro. | 2002 Mar |
|
| 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 |
|
| 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 |
|
| Effects of the endothelin-1 receptor antagonist tezosentan on renal blood flow and diuresis during prolonged increased intra-abdominal pressure. | 2003 Nov |
|
| Pharmacological therapy of acute cardiogenic pulmonary oedema in the emergency department. | 2004 Feb |
|
| Novel endothelin receptor antagonist attenuates endotoxin-induced lung injury in sheep. | 2004 Mar |
|
| Differentiated and dose-related cardiovascular effects of a dual endothelin receptor antagonist in endotoxin shock. | 2004 May |
|
| Clinical trials update from the American College of Cardiology meeting: CARE-HF and the remission of heart failure, Women's Health Study, TNT, COMPASS-HF, VERITAS, CANPAP, PEECH and PREMIER. | 2005 Aug |
|
| Combination pharmacologic therapies for heart failure: what next after angiotensin-converting enzyme inhibitors and beta-blockers? | 2005 Aug |
|
| Contribution of endothelin to coronary vasomotor tone is abolished after myocardial infarction. | 2005 Feb |
|
| Nitric oxide blunts the endothelin-mediated pulmonary vasoconstriction in exercising swine. | 2005 Oct 15 |
|
| Overview of randomized clinical trials in acute heart failure syndromes. | 2005 Sep 19 |
|
| Endothelin-2 in ovarian follicle rupture. | 2006 Apr |
|
| Tezosentan decreases pulmonary artery pressure and improves survival rate in an animal model of meconium aspiration. | 2006 Jan |
|
| 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 |
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
Sat Dec 16 17:06:08 GMT 2023
by
admin
on
Sat Dec 16 17:06:08 GMT 2023
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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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