This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.
Identification
- Generic Name
- Tezosentan
- DrugBank Accession Number
- DB06558
- Background
Tezosentan is an intravenous endothelin receptor A/B antagonist. Tezosentan was initially developed for vasodilation in patients with acute heart failure but studies have shown that it does not assist in the treatment of dyspnea or prevent cardiovascular events.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
Structure for Tezosentan (DB06558)
- Weight
- Average: 605.625
Monoisotopic: 605.180500331 - Chemical Formula
- C27H27N9O6S
- Synonyms
- Tezosentan
- External IDs
- ACT-050089
Pharmacology
- Indication
Investigated for use/treatment in congestive heart failure, liver disease, and heart disease.
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Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Not Available
- Mechanism of action
Target Actions Organism UEndothelin-1 receptor Not Available Humans UEndothelin B receptor Not Available Humans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
A pronounced and rapid disposition phase (half-life 6 min), accounting for the major part of the elimination, was followed by a slower phase (half-life 3 h), probably caused by distribution from tissues.
- Clearance
Not Available
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareIloprost Iloprost may increase the hypotensive activities of Tezosentan. Isosorbide mononitrate Tezosentan may increase the vasodilatory activities of Isosorbide mononitrate. Patent Blue The therapeutic efficacy of Tezosentan can be decreased when used in combination with Patent Blue. - Food Interactions
- Not Available
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as pyridinylpyrimidines. These are compounds containing a pyridinylpyrimidine skeleton, which consists of a pyridine linked (not fused) to a pyrimidine by a bond.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Diazines
- Sub Class
- Pyrimidines and pyrimidine derivatives
- Direct Parent
- Pyridinylpyrimidines
- Alternative Parents
- Diarylethers / Pyridinesulfonamides / Anisoles / Methoxybenzenes / Phenoxy compounds / Alkyl aryl ethers / Imidolactams / Organosulfonamides / Aminosulfonyl compounds / Heteroaromatic compounds show 7 more
- Substituents
- Alcohol / Alkyl aryl ether / Aminosulfonyl compound / Anisole / Aromatic heteromonocyclic compound / Azacycle / Azole / Benzenoid / Diaryl ether / Ether show 23 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 64J9J55263
- CAS number
- 180384-57-0
- InChI Key
- TUYWTLTWNJOZNY-UHFFFAOYSA-N
- InChI
- 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)
- IUPAC Name
- N-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-[2-(2H-1,2,3,4-tetrazol-5-yl)pyridin-4-yl]pyrimidin-4-yl]-5-(propan-2-yl)pyridine-2-sulfonamide
- SMILES
- COC1=CC=CC=C1OC1=C(NS(=O)(=O)C2=NC=C(C=C2)C(C)C)N=C(N=C1OCCO)C1=CC(=NC=C1)C1=NNN=N1
References
- General References
- Cotter G, Kiowski W, Kaluski E, Kobrin I, Milovanov O, Marmor A, Jafari J, Reisin L, Krakover R, Vered Z, Caspi A: 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. Eur J Heart Fail. 2001 Aug;3(4):457-61. [Article]
- Dingemanse J, Clozel M, van Giersbergen PL: Entry-into-humans study with tezosentan, an intravenous dual endothelin receptor antagonist. J Cardiovasc Pharmacol. 2002 Jun;39(6):795-802. [Article]
- External Links
- PubChem Compound
- 151174
- ChemSpider
- 133242
- BindingDB
- 50143800
- ChEMBL
- CHEMBL61780
- ZINC
- ZINC000003954692
- Wikipedia
- Tezosentan
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 3 Completed Treatment Acute Decompensation of Chronic Heart Failure / Acute Heart Failure (AHF) / New Onset of Heart Failure 2 3 Terminated Treatment Cardiovascular Disease (CVD) / Pulmonary Hypertension (PH) 1 2 Terminated Supportive Care Pulmonary Arterial Hypertension (PAH) 1 2 Terminated Treatment Pulmonary Arterial Hypertension (PAH) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.0298 mg/mL ALOGPS logP 2.96 ALOGPS logP 4.34 Chemaxon logS -4.3 ALOGPS pKa (Strongest Acidic) 5 Chemaxon pKa (Strongest Basic) 3.1 Chemaxon Physiological Charge -2 Chemaxon Hydrogen Acceptor Count 12 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 200.11 Å2 Chemaxon Rotatable Bond Count 11 Chemaxon Refractivity 178.23 m3·mol-1 Chemaxon Polarizability 61.25 Å3 Chemaxon Number of Rings 5 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.8053 Blood Brain Barrier - 0.8147 Caco-2 permeable - 0.782 P-glycoprotein substrate Non-substrate 0.6576 P-glycoprotein inhibitor I Non-inhibitor 0.6773 P-glycoprotein inhibitor II Non-inhibitor 0.5604 Renal organic cation transporter Non-inhibitor 0.885 CYP450 2C9 substrate Non-substrate 0.6555 CYP450 2D6 substrate Non-substrate 0.9116 CYP450 3A4 substrate Non-substrate 0.5 CYP450 1A2 substrate Non-inhibitor 0.6946 CYP450 2C9 inhibitor Inhibitor 0.5761 CYP450 2D6 inhibitor Non-inhibitor 0.8573 CYP450 2C19 inhibitor Non-inhibitor 0.5 CYP450 3A4 inhibitor Inhibitor 0.8754 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.8735 Ames test Non AMES toxic 0.5826 Carcinogenicity Non-carcinogens 0.6159 Biodegradation Not ready biodegradable 0.9944 Rat acute toxicity 2.3904 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9497 hERG inhibition (predictor II) Non-inhibitor 0.6165
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 264.6787886 predictedDarkChem Lite v0.1.0 [M-H]- 223.07042 predictedDeepCCS 1.0 (2019) [M+H]+ 265.0853886 predictedDarkChem Lite v0.1.0 [M+H]+ 225.27022 predictedDeepCCS 1.0 (2019) [M+Na]+ 265.3068886 predictedDarkChem Lite v0.1.0 [M+Na]+ 231.18274 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Phosphatidylinositol phospholipase c activity
- Specific Function
- Receptor for endothelin-1. Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of binding affinities for ET-A is:...
- Gene Name
- EDNRA
- Uniprot ID
- P25101
- Uniprot Name
- Endothelin-1 receptor
- Molecular Weight
- 48721.76 Da
References
- Urbanowicz W, Sogni P, Moreau R, Tazi KA, Barriere E, Poirel O, Martin A, Guimont MC, Cazals-Hatem D, Lebrec D: Tezosentan, an endothelin receptor antagonist, limits liver injury in endotoxin challenged cirrhotic rats. Gut. 2004 Dec;53(12):1844-9. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Peptide hormone binding
- Specific Function
- Non-specific receptor for endothelin 1, 2, and 3. Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system.
- Gene Name
- EDNRB
- Uniprot ID
- P24530
- Uniprot Name
- Endothelin B receptor
- Molecular Weight
- 49643.255 Da
References
- Urbanowicz W, Sogni P, Moreau R, Tazi KA, Barriere E, Poirel O, Martin A, Guimont MC, Cazals-Hatem D, Lebrec D: Tezosentan, an endothelin receptor antagonist, limits liver injury in endotoxin challenged cirrhotic rats. Gut. 2004 Dec;53(12):1844-9. [Article]
Drug created at March 19, 2008 16:36 / Updated at February 21, 2021 18:52