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Identification
NameSaprisartan
Accession NumberDB01347
Typesmall molecule
Groupsapproved
Description

Saprisartan is an AT1 receptor antagonist. It is based on medications of losartan’s prototypical chemical structure. The mode of (functional) AT1 receptor antagonism has been characterized as insurmountable/noncompetitive for saprisartan. It is very likely that slow dissociation kinetics from the AT1 receptor underlie insurmountable antagonism.(10579749)

Structure
Thumb
SynonymsNot Available
SaltsNot Available
Brand namesNot Available
Brand mixturesNot Available
CategoriesNot Available
CAS number146623-69-0
WeightAverage: 611.431
Monoisotopic: 610.049723164
Chemical FormulaC25H22BrF3N4O4S
InChI KeyInChIKey=DUEWVPTZCSAMNB-UHFFFAOYSA-N
InChI
InChI=1S/C25H22BrF3N4O4S/c1-2-19-31-21(14-8-9-14)22(24(30)34)33(19)12-13-7-10-18-16(11-13)20(26)23(37-18)15-5-3-4-6-17(15)32-38(35,36)25(27,28)29/h3-7,10-11,14,32H,2,8-9,12H2,1H3,(H2,30,34)
IUPAC Name
1-({3-bromo-2-[2-(trifluoromethane)sulfonamidophenyl]-1-benzofuran-5-yl}methyl)-4-cyclopropyl-2-ethyl-1H-imidazole-5-carboxamide
SMILES
CCC1=NC(C2CC2)=C(N1CC1=CC2=C(OC(=C2Br)C2=CC=CC=C2NS(=O)(=O)C(F)(F)F)C=C1)C(N)=O
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassBenzofurans
SubclassPhenylbenzofurans
Direct parent2-Phenylbenzofurans
Alternative parentsStilbenes; Sulfanilides; Carbonylimidazoles; Aryl Bromides; N-substituted Imidazoles; Sulfonyls; Furans; Sulfonamides; Cyclic Alcohols and Derivatives; Primary Carboxylic Acid Amides; Enolates; Polyamines; Carboxylic Acids; Organofluorides; Organobromides; Alkyl Fluorides; 1,2,4,5-trisubstituted Imidazoles
Substituentssulfanilide; 1,2,4,5-tetrasubstituted imidazole; imidazole-4-carbonyl group; n-substituted imidazole; aryl bromide; benzene; aryl halide; furan; azole; sulfonyl; sulfonic acid derivative; sulfonamide; cyclic alcohol; imidazole; primary carboxylic acid amide; carboxamide group; carboxylic acid; carboxylic acid derivative; polyamine; enolate; amine; organohalogen; organobromide; organofluoride; organonitrogen compound; alkyl halide; alkyl fluoride
Classification descriptionThis compound belongs to the 2-phenylbenzofurans.
Pharmacology
IndicationSaprisartan is used in the treatment of hypertension and heart failure.
PharmacodynamicsBy inhibiting the angiotensin II receptor, this drug leades to a decrease in sodium reabsorption and a decrease in vasoconstriction. This has the combined effect of decreasing blood pressure.
Mechanism of actionSaprisartan is a selective, potent, orally active and long-acting nonpeptide Angiotensin II type 1 (AT1) receptor antagonist. Saprisartan 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. Saprisartan 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 organisms
  • Humans and other mammals
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 + 0.647
Caco-2 permeable - 0.6148
P-glycoprotein substrate Substrate 0.5611
P-glycoprotein inhibitor I Non-inhibitor 0.6454
P-glycoprotein inhibitor II Non-inhibitor 0.5279
Renal organic cation transporter Non-inhibitor 0.8625
CYP450 2C9 substrate Non-substrate 0.653
CYP450 2D6 substrate Non-substrate 0.7866
CYP450 3A4 substrate Substrate 0.5105
CYP450 1A2 substrate Non-inhibitor 0.6561
CYP450 2C9 substrate Inhibitor 0.6267
CYP450 2D6 substrate Non-inhibitor 0.7996
CYP450 2C19 substrate Inhibitor 0.5274
CYP450 3A4 substrate Non-inhibitor 0.5167
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.8837
Ames test Non AMES toxic 0.5853
Carcinogenicity Non-carcinogens 0.6378
Biodegradation Not ready biodegradable 1.0
Rat acute toxicity 2.5781 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9673
hERG inhibition (predictor II) Inhibitor 0.6568
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
water solubility1.51e-02 g/lALOGPS
logP5.89ALOGPS
logP3.35ChemAxon
logS-4.6ALOGPS
pKa (strongest acidic)2.27ChemAxon
pKa (strongest basic)5.18ChemAxon
physiological charge-1ChemAxon
hydrogen acceptor count4ChemAxon
hydrogen donor count2ChemAxon
polar surface area120.22ChemAxon
rotatable bond count8ChemAxon
refractivity137.15ChemAxon
polarizability54.2ChemAxon
number of rings5ChemAxon
bioavailability1ChemAxon
rule of fiveNoChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleYesChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
ResourceLink
PubChem Compound60921
PubChem Substance46508176
ChemSpider54892
Therapeutic Targets DatabaseDAP001257
PharmGKBPA164746338
ATC CodesNot Available
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. Timmermans PB: Pharmacological properties of angiotensin II receptor antagonists. Can J Cardiol. 1999 Nov;15 Suppl F:26F-8F. Pubmed
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

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