Identification

Name
Tasosartan
Accession Number
DB01349
Type
Small Molecule
Groups
Experimental
Description

Tasosartan is a long-acting angiotensin II (AngII) receptor blocker. Its long duration of action has been attributed to its active metabolite enoltasosartan. It is used to treat patients with essential hypertension

Structure
Thumb
Synonyms
  • Tasosartan
  • WAY-ana-756
External IDs
ANA-756
Categories
UNII
48G92V856H
CAS number
145733-36-4
Weight
Average: 411.4591
Monoisotopic: 411.180758329
Chemical Formula
C23H21N7O
InChI Key
ADXGNEYLLLSOAR-UHFFFAOYSA-N
InChI
InChI=1S/C23H21N7O/c1-14-18-11-12-21(31)30(23(18)25-15(2)24-14)13-16-7-9-17(10-8-16)19-5-3-4-6-20(19)22-26-28-29-27-22/h3-10H,11-13H2,1-2H3,(H,26,27,28,29)
IUPAC Name
2,4-dimethyl-8-({4-[2-(2H-1,2,3,4-tetrazol-5-yl)phenyl]phenyl}methyl)-5H,6H,7H,8H-pyrido[2,3-d]pyrimidin-7-one
SMILES
CC1=NC(C)=C2CCC(=O)N(CC3=CC=C(C=C3)C3=CC=CC=C3C3=NNN=N3)C2=N1

Pharmacology

Indication

Tasosartan is infrequently in the treatment of hypertension and heart failure.

Pharmacodynamics

By blocking the angiotensin II (AT1) receptor, the drug ultimately causes vasodilation, reduced secretion of vasopressin (ADH), reduced production and secretion of aldosterone, amongst other actions leading to the combined effect of a reduction of blood pressure.

Mechanism of action

Tasosartan is a selective, potent, orally active and long-acting nonpeptide Angiotensin II type 1 (AT1) receptor antagonist. Tasosartan blocks the renin-angiotensin-aldosterone system (RAAS) at the level of the AT1 receptor that mediates most, if not all, of the important actions of Ang II. Tasosartan binds reversibly to the AT1 receptors in vascular smooth muscle and the adrenal gland. As angiotensin II is a vasoconstrictor, which also stimulates the synthesis and release of aldosterone, blockage of its effects results in decreases in systemic vascular resistance. AT1 receptor antagonists avoid the nonspecificity of the Ang I converting enzyme (ACE) inhibitors.

TargetActionsOrganism
AType-1 angiotensin II receptor
antagonist
Human
UType-2 angiotensin II receptor
antagonist
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(4R)-limoneneThe risk or severity of adverse effects can be increased when Tasosartan is combined with (4R)-limonene.
AcebutololThe risk or severity of hyperkalemia can be increased when Tasosartan is combined with Acebutolol.
AceclofenacThe risk or severity of adverse effects can be increased when Tasosartan is combined with Aceclofenac.
AcemetacinThe risk or severity of adverse effects can be increased when Tasosartan is combined with Acemetacin.
Acetyl sulfisoxazoleThe metabolism of Tasosartan can be decreased when combined with Acetyl sulfisoxazole.
Acetylsalicylic acidThe risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Tasosartan is combined with Acetylsalicylic acid.
AlclofenacThe risk or severity of adverse effects can be increased when Tasosartan is combined with Alclofenac.
AliskirenAliskiren may increase the hyperkalemic activities of Tasosartan.
AlminoprofenThe risk or severity of adverse effects can be increased when Tasosartan is combined with Alminoprofen.
AmilorideThe risk or severity of hyperkalemia can be increased when Tasosartan is combined with Amiloride.
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0015439
PubChem Compound
60919
PubChem Substance
46504809
ChemSpider
54890
BindingDB
50040439
ChEBI
135666
ChEMBL
CHEMBL432162
Therapeutic Targets Database
DAP001258
PharmGKB
PA164769057
Wikipedia
Tasosartan
ATC Codes
C09CA05 — Tasosartan

Clinical Trials

Clinical Trials
Not Available

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 Solubility0.0325 mg/mLALOGPS
logP3.07ALOGPS
logP4.18ChemAxon
logS-4.1ALOGPS
pKa (Strongest Acidic)7.4ChemAxon
pKa (Strongest Basic)2.79ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area100.55 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity130.61 m3·mol-1ChemAxon
Polarizability44.34 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9849
Caco-2 permeable+0.5626
P-glycoprotein substrateSubstrate0.5771
P-glycoprotein inhibitor IInhibitor0.7645
P-glycoprotein inhibitor IIInhibitor0.5378
Renal organic cation transporterInhibitor0.524
CYP450 2C9 substrateNon-substrate0.7978
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.7408
CYP450 1A2 substrateNon-inhibitor0.864
CYP450 2C9 inhibitorInhibitor0.6924
CYP450 2D6 inhibitorInhibitor0.5465
CYP450 2C19 inhibitorInhibitor0.8163
CYP450 3A4 inhibitorInhibitor0.5112
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8338
Ames testNon AMES toxic0.5066
CarcinogenicityNon-carcinogens0.8061
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.8079 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.6971
hERG inhibition (predictor II)Non-inhibitor0.5487
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 GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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 biphenyls and derivatives. These are organic compounds containing to benzene rings linked together by a C-C bond.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Biphenyls and derivatives
Direct Parent
Biphenyls and derivatives
Alternative Parents
Phenyltetrazoles and derivatives / Pyridopyrimidines / Pyrimidines and pyrimidine derivatives / Pyridines and derivatives / Imidolactams / Tertiary carboxylic acid amides / Heteroaromatic compounds / Lactams / Azacyclic compounds / Organopnictogen compounds
show 4 more
Substituents
Biphenyl / Phenyltetrazole / Pyridopyrimidine / Pyridine / Pyrimidine / Imidolactam / Azole / Tertiary carboxylic acid amide / Tetrazole / Heteroaromatic compound
show 14 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Protein heterodimerization activity
Specific Function
Receptor for angiotensin II. Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system.
Gene Name
AGTR1
Uniprot ID
P30556
Uniprot Name
Type-1 angiotensin II receptor
Molecular Weight
41060.53 Da
References
  1. Elokdah HM, Friedrichs GS, Chai SY, Harrison BL, Primeau J, Chlenov M, Crandall DL: Novel human metabolites of the angiotensin-II antagonist tasosartan and their pharmacological effects. Bioorg Med Chem Lett. 2002 Aug 5;12(15):1967-71. [PubMed:12113820]
  2. Unger T: Pharmacology of AT1-receptor blockers. Blood Press Suppl. 2001;(3):5-10. [PubMed:11683476]
  3. Maillard MP, Rossat J, Brunner HR, Burnier M: Tasosartan, enoltasosartan, and angiotensin II receptor blockade: the confounding role of protein binding. J Pharmacol Exp Ther. 2000 Nov;295(2):649-54. [PubMed:11046101]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Receptor antagonist activity
Specific Function
Receptor for angiotensin II. Cooperates with MTUS1 to inhibit ERK2 activation and cell proliferation.
Gene Name
AGTR2
Uniprot ID
P50052
Uniprot Name
Type-2 angiotensin II receptor
Molecular Weight
41183.45 Da
References
  1. Unger T: Pharmacology of AT1-receptor blockers. Blood Press Suppl. 2001;(3):5-10. [PubMed:11683476]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]

Drug created on June 30, 2007 12:15 / Updated on October 01, 2018 13:02