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 |
|---|---|---|
| NO and prostanoids blunt endothelin-mediated coronary vasoconstrictor influence in exercising swine. | 2006-11 |
|
| Role of endothelin receptor activation in secondary pulmonary hypertension in awake swine after myocardial infarction. | 2006-07-15 |
|
| Nebulized therapies for childhood pulmonary hypertension: an in vitro model. | 2006-07 |
|
| The role of indomethacin and tezosentan on renal effects induced by Bothrops moojeni Lys49 myotoxin I. | 2006-06-15 |
|
| Endothelin receptors in light-induced retinal degeneration. | 2006-06 |
|
| Effects of endothelin receptor antagonism on acute lung injury induced by chlorine gas. | 2006-06 |
|
| Endothelin receptor antagonists. | 2006-06 |
|
| Nitric oxide-endothelin-1 interactions after surgically induced acute increases in pulmonary blood flow in intact lambs. | 2006-05 |
|
| Effects of endothelin antagonist tezosentan on orthodontic tooth movement in rats. | 2006-04 |
|
| Comparison of the pharmacokinetics, pharmacodynamics and tolerability of tezosentan between caucasian and Japanese subjects. | 2006-04 |
|
| Endothelin-2 in ovarian follicle rupture. | 2006-04 |
|
| The role of endothelin-1 in hyperoxia-induced lung injury in mice. | 2006-03-27 |
|
| [Medical and ventilatory treatment of acute heart failure]. | 2006-03-09 |
|
| Optimizing outcomes in the patient with acute decompensated heart failure. | 2006-03 |
|
| Newer approaches to the pharmacological management of heart failure. | 2006-02 |
|
| Tezosentan decreases pulmonary artery pressure and improves survival rate in an animal model of meconium aspiration. | 2006-01 |
|
| Year in review 2005: Critical Care--respirology: mechanical ventilation, infection, monitoring, and education. | 2006 |
|
| Medical and ventilatory treatment of acute heart failure: new insights. | 2006 |
|
| Nitric oxide blunts the endothelin-mediated pulmonary vasoconstriction in exercising swine. | 2005-10-15 |
|
| Carbon monoxide, but not endothelin-1, plays a major role for the hepatic microcirculation in a murine model of early systemic inflammation. | 2005-10 |
|
| Endothelin-1 causes systemic vasodilatation in anaesthetised turtles (Trachemys scripta) through activation of ETB-receptors. | 2005-10 |
|
| Pharmacology of new agents for acute heart failure syndromes. | 2005-09-19 |
|
| Overview of randomized clinical trials in acute heart failure syndromes. | 2005-09-19 |
|
| Renal blood flow in sepsis. | 2005-08 |
|
| 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. | 2005-08 |
|
| Echocardiographic ejection fraction in patients with acute heart failure: correlations with hemodynamic, clinical, and neurohormonal measures and short-term outcome. | 2005-08 |
|
| Combination pharmacologic therapies for heart failure: what next after angiotensin-converting enzyme inhibitors and beta-blockers? | 2005-08 |
|
| Tezosentan in patients with acute heart failure: design of the Value of Endothelin Receptor Inhibition with Tezosentan in Acute heart failure Study (VERITAS). | 2005-07 |
|
| Endothelin antagonists: new bullets against lung injury? | 2005-06 |
|
| Tezosentan-induced attenuation of lung injury in endotoxemic sheep is associated with reduced activation of protein kinase C. | 2005-06 |
|
| Role of endothelin in alpha-adrenoceptor coronary vasoconstriction. | 2005-04 |
|
| Effects of a dual endothelin-1 receptor antagonist on airway obstruction and acute lung injury in sheep following smoke inhalation and burn injury. | 2005-03 |
|
| Contribution of endothelin to coronary vasomotor tone is abolished after myocardial infarction. | 2005-02 |
|
| Tezosentan reduces the microvascular filtration coefficient in isolated lungs from rats subjected to cecum ligation and puncture. | 2005 |
|
| Tezosentan in the management of decompensated heart failure. | 2004-12-15 |
|
| Tezosentan, an endothelin receptor antagonist, limits liver injury in endotoxin challenged cirrhotic rats. | 2004-12 |
|
| Tezosentan, another selective selection for pulmonary hypertension, or not? | 2004-11 |
|
| Tezosentan, a combined parenteral endothelin receptor antagonist, produces pulmonary vasodilation in lambs with acute and chronic pulmonary hypertension. | 2004-11 |
|
| The hemodynamic and neurohormonal effects of low doses of tezosentan (an endothelin A/B receptor antagonist) in patients with acute heart failure. | 2004-08 |
|
| 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). | 2004-06-01 |
|
| Tezosentan counteracts endotoxin-induced pulmonary edema and improves gas exchange. | 2004-06 |
|
| Differentiated and dose-related cardiovascular effects of a dual endothelin receptor antagonist in endotoxin shock. | 2004-05 |
|
| Novel endothelin receptor antagonist attenuates endotoxin-induced lung injury in sheep. | 2004-03 |
|
| Nitric oxide synthase inhibition and elevated endothelin increase oxygen consumption but do not affect glucose and palmitate oxidation in the isolated rat heart. | 2004-03 |
|
| Influence of mild liver impairment on the pharmacokinetics of tezosentan, a drug excreted unchanged into bile. | 2004-03 |
|
| Acute cardiopulmonary effects of a dual-endothelin receptor antagonist on oleic acid-induced pulmonary arterial hypertension in dogs. | 2004-02-18 |
|
| Pharmacological therapy of acute cardiogenic pulmonary oedema in the emergency department. | 2004-02 |
|
| Endogenous endothelin increases gallbladder tone and leads to acute cholecystitis in the Australian possum. | 2004-02 |
|
| Role of endothelin-1 and thromboxane A2 in the pulmonary hypertension induced by heparin-protamine interaction in anesthetized dogs. | 2004-01 |
|
| Comparison of the role of endothelin, vasopressin and angiotensin in arterial pressure regulation during sevoflurane anaesthesia in dogs. | 2004-01 |
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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