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Identification
NameTasosartan
Accession NumberDB01349
Typesmall molecule
Groupsapproved
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
SynonymsNot Available
SaltsNot Available
Brand namesNot Available
Brand mixturesNot Available
CategoriesNot Available
CAS number145733-36-4
WeightAverage: 411.4591
Monoisotopic: 411.180758329
Chemical FormulaC23H21N7O
InChI KeyInChIKey=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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassAzoles
SubclassTetrazoles
Direct parentBiphenyltetrazoles and Derivatives
Alternative parentsBiphenyls and Derivatives; Pyridopyrimidines; Pyrimidines and Pyrimidine Derivatives; Pyridines and Derivatives; Tertiary Carboxylic Acid Amides; Tertiary Amines; Carboxylic Acids; Polyamines
Substituentsbiphenyl; pyridopyrimidine; pyrimidine; benzene; pyridine; tertiary carboxylic acid amide; tertiary amine; carboxamide group; polyamine; carboxylic acid derivative; carboxylic acid; amine; organonitrogen compound
Classification descriptionThis compound belongs to the biphenyltetrazoles and derivatives. These are organic compounds containing a biphenyl attached to a tetrazole. A carbon atom of the biphenyl moiety is boned to a carbon or the nitrogen atom of the tetrazole moiety.
Pharmacology
IndicationTasosartan is infrequently in the treatment of hypertension and heart failure.
PharmacodynamicsBy 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 actionTasosartan 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.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organismsNot Available
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 1.0
Blood Brain Barrier + 0.9849
Caco-2 permeable + 0.5626
P-glycoprotein substrate Substrate 0.5771
P-glycoprotein inhibitor I Inhibitor 0.7645
P-glycoprotein inhibitor II Inhibitor 0.5378
Renal organic cation transporter Inhibitor 0.524
CYP450 2C9 substrate Non-substrate 0.7978
CYP450 2D6 substrate Non-substrate 0.9116
CYP450 3A4 substrate Substrate 0.7408
CYP450 1A2 substrate Non-inhibitor 0.864
CYP450 2C9 substrate Inhibitor 0.6924
CYP450 2D6 substrate Inhibitor 0.5465
CYP450 2C19 substrate Inhibitor 0.8163
CYP450 3A4 substrate Inhibitor 0.5112
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.8338
Ames test Non AMES toxic 0.5066
Carcinogenicity Non-carcinogens 0.8061
Biodegradation Not ready biodegradable 1.0
Rat acute toxicity 2.8079 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.6971
hERG inhibition (predictor II) Non-inhibitor 0.5487
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
water solubility3.25e-02 g/lALOGPS
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 area100.55ChemAxon
rotatable bond count4ChemAxon
refractivity130.61ChemAxon
polarizability44.34ChemAxon
number of rings5ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
ResourceLink
PubChem Compound60919
PubChem Substance46504809
ChemSpider54890
BindingDB50040439
Therapeutic Targets DatabaseDAP001258
PharmGKBPA164769057
WikipediaTasosartan
ATC CodesC09CA05
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AmilorideIncreased risk of hyperkalemia
LithiumThe ARB increases serum levels of lithium
PotassiumIncreased risk of hyperkalemia
TriamtereneIncreased risk of hyperkalemia
Food InteractionsNot Available

1. Type-1 angiotensin II receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Type-1 angiotensin II receptor P30556 Details

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
  2. Unger T: Pharmacology of AT1-receptor blockers. Blood Press Suppl. 2001;(3):5-10. Pubmed
  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
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Type-2 angiotensin II receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Type-2 angiotensin II receptor P50052 Details

References:

  1. Unger T: Pharmacology of AT1-receptor blockers. Blood Press Suppl. 2001;(3):5-10. Pubmed

1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

Comments
Drug created on June 30, 2007 12:15 / Updated on September 16, 2013 17:14