DrugBank: Tasosartan (DB01349)

targets (2) enzymes (1)

Identification

Name

Tasosartan

Accession Number

DB01349

Type

small molecule

Groups

approved

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

Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure

Synonyms

Not Available

Salts

Not Available

Brand names

Not Available

Brand mixtures

Not Available

Categories

Not Available

CAS number

145733-36-4

Weight

Average: 411.4591
Monoisotopic: 411.180758329

Chemical Formula

C₂₃H₂₁N₇O

InChI Key

InChIKey=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)

Plain Text

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

Plain Text

Mass Spec

Not Available

Taxonomy

Kingdom

Organic

Classes

Biphenyltetrazoles and Derivatives
Lactams

Substructures

Amino Ketones
Phenylpropenes
Benzene and Derivatives
Aliphatic and Aryl Amines
Biphenyl and Derivatives
Biphenyltetrazoles and Derivatives
Pyrimidines and Derivatives
Tetrazoles
Phenyltetrazoles and Derivatives
Heterocyclic compounds
Aromatic compounds
Carboxamides and Derivatives
Lactams
Imines
Cyanamides

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.

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

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	3.25e-02 g/l	ALOGPS
logP	3.07	ALOGPS
logP	4.18	ChemAxon
logS	-4.1	ALOGPS
pKa (strongest acidic)	7.4	ChemAxon
pKa (strongest basic)	2.79	ChemAxon
physiological charge	0	ChemAxon
hydrogen acceptor count	6	ChemAxon
hydrogen donor count	1	ChemAxon
polar surface area	100.55	ChemAxon
rotatable bond count	4	ChemAxon
refractivity	130.61	ChemAxon
polarizability	44.34	ChemAxon

References

Synthesis Reference

Not Available

General Reference

Not Available

External Links

Resource	Link
PubChem Compound	60919
PubChem Substance	46504809
ChemSpider	54890
BindingDB	50040439
Therapeutic Targets Database	DAP001258
PharmGKB	PA164769057
Wikipedia	http://en.wikipedia.org/wiki/Tasosartan

ATC Codes

C09CA05

AHFS Codes

Not Available

PDB Entries

Not Available

FDA label

Not Available

MSDS

Not Available

Interactions

Drug Interactions

Drug	Interaction
Amiloride	Increased risk of hyperkalemia
Lithium	The ARB increases serum levels of lithium
Potassium	Increased risk of hyperkalemia
Triamterene	Increased risk of hyperkalemia

Food Interactions

Not Available

Targets
1. Type-1 angiotensin II receptor Pharmacological action: yes Actions: antagonist Receptor for angiotensin II. Mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system Organism class: human UniProt ID: P30556 Gene: AGTR1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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 Unger T: Pharmacology of AT1-receptor blockers. Blood Press Suppl. 2001;(3):5-10. Pubmed 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 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 Pharmacological action: unknown Actions: antagonist Receptor for angiotensin II. Cooperates with MTUS1 to inhibit ERK2 activation and cell proliferation Organism class: human UniProt ID: P50052 Gene: AGTR2 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Unger T: Pharmacology of AT1-receptor blockers. Blood Press Suppl. 2001;(3):5-10. Pubmed

Targets

1. Type-1 angiotensin II receptor

Pharmacological action: yes
Actions: antagonist

Receptor for angiotensin II. Mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system

Organism class: human
UniProt ID: P30556 Link_out

Gene: AGTR1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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

Pharmacological action: unknown
Actions: antagonist

Receptor for angiotensin II. Cooperates with MTUS1 to inhibit ERK2 activation and cell proliferation

Organism class: human
UniProt ID: P50052 Link_out

Gene: AGTR2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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

Enzymes
1. Cytochrome P450 3A4 Actions: substrate 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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide UniProt ID: P08684 Gene: CYP3A4 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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

Enzymes

1. Cytochrome P450 3A4

Actions: substrate

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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out

Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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 February 08, 2013 16:20