Tezosentan

This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

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Name
Tezosentan
Accession Number
DB06558
Type
Small Molecule
Groups
Investigational
Description

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.

Structure
Thumb
Synonyms
Not Available
External IDs
ACT-050089
Categories
UNII
64J9J55263
CAS number
180384-57-0
Weight
Average: 605.625
Monoisotopic: 605.180500331
Chemical Formula
C27H27N9O6S
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

Pharmacology

Indication

Investigated for use/treatment in congestive heart failure, liver disease, and heart disease.

Pharmacodynamics
Not Available
Mechanism of action
TargetActionsOrganism
UEndothelin-1 receptorNot AvailableHumans
UEndothelin B receptorNot AvailableHumans
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
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
Patent BlueThe therapeutic efficacy of Tezosentan can be decreased when used in combination with Patent Blue.
Additional Data Available
  • Extended Description
    Extended Description

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

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  • Action
    Action

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Food Interactions
Not Available

References

General References
  1. 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. [PubMed:11511432]
  2. 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. [PubMed:12021573]
External Links
PubChem Compound
151174
ChemSpider
133242
BindingDB
50143800
ChEMBL
CHEMBL61780
Wikipedia
Tezosentan

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2TerminatedSupportive CarePulmonary Arterial Hypertension (PAH)1
2TerminatedTreatmentPulmonary Arterial Hypertension (PAH)1
3CompletedTreatmentAcute Decompensation of Chronic Heart Failure / Acute Heart Failure (AHF) / New Onset of Heart Failure2
3TerminatedTreatmentHeart Diseases / Pulmonary Hypertension (PH)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
PropertyValueSource
Water Solubility0.0298 mg/mLALOGPS
logP2.96ALOGPS
logP4.34ChemAxon
logS-4.3ALOGPS
pKa (Strongest Acidic)5.2ChemAxon
pKa (Strongest Basic)2.11ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count12ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area200.11 Å2ChemAxon
Rotatable Bond Count11ChemAxon
Refractivity178.23 m3·mol-1ChemAxon
Polarizability61.25 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.8053
Blood Brain Barrier-0.8147
Caco-2 permeable-0.782
P-glycoprotein substrateNon-substrate0.6576
P-glycoprotein inhibitor INon-inhibitor0.6773
P-glycoprotein inhibitor IINon-inhibitor0.5604
Renal organic cation transporterNon-inhibitor0.885
CYP450 2C9 substrateNon-substrate0.6555
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.5
CYP450 1A2 substrateNon-inhibitor0.6946
CYP450 2C9 inhibitorInhibitor0.5761
CYP450 2D6 inhibitorNon-inhibitor0.8573
CYP450 2C19 inhibitorNon-inhibitor0.5
CYP450 3A4 inhibitorInhibitor0.8754
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8735
Ames testNon AMES toxic0.5826
CarcinogenicityNon-carcinogens0.6159
BiodegradationNot ready biodegradable0.9944
Rat acute toxicity2.3904 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9497
hERG inhibition (predictor II)Non-inhibitor0.6165
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

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
Pyridinylpyrimidine / Diaryl ether / Pyridine-2-sulfonamide / Phenoxy compound / Anisole / Phenol ether / Methoxybenzene / Alkyl aryl ether / Monocyclic benzene moiety / Pyridine
show 23 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available

Targets

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
  1. 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. [PubMed:15542526]
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
  1. 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. [PubMed:15542526]

Drug created on March 19, 2008 10:36 / Updated on June 04, 2019 06:25