Identification

Name
Saprisartan
Accession Number
DB01347
Type
Small Molecule
Groups
Experimental
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 [1].

Structure
Thumb
Synonyms
Not Available
Product Ingredients
IngredientUNIICASInChI Key
Saprisartan potassiumT28707PG7T146613-90-3IASZJGRIPLTJMA-UHFFFAOYSA-N
Categories
UNII
HS64NG1G69
CAS number
146623-69-0
Weight
Average: 611.431
Monoisotopic: 610.049723164
Chemical Formula
C25H22BrF3N4O4S
InChI Key
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-trifluoromethanesulfonamidophenyl)-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

Pharmacology

Indication

Saprisartan is used in the treatment of hypertension and heart failure.

Pharmacodynamics

By 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 action

Saprisartan 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.

TargetActionsOrganism
AType-1 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
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(4R)-limoneneThe risk or severity of adverse effects can be increased when Saprisartan is combined with (4R)-limonene.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline may increase the hypotensive activities of Saprisartan.
AcebutololAcebutolol may increase the hypotensive activities of Saprisartan.
AceclofenacThe risk or severity of adverse effects can be increased when Saprisartan is combined with Aceclofenac.
AcemetacinThe therapeutic efficacy of Saprisartan can be decreased when used in combination with Acemetacin.
Acetylsalicylic acidThe risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Saprisartan is combined with Acetylsalicylic acid.
AlclofenacThe risk or severity of adverse effects can be increased when Saprisartan is combined with Alclofenac.
AlfuzosinAlfuzosin may increase the hypotensive activities of Saprisartan.
AliskirenAliskiren may increase the hyperkalemic activities of Saprisartan.
AlminoprofenThe risk or severity of adverse effects can be increased when Saprisartan is combined with Alminoprofen.
Food Interactions
Not Available

References

General References
  1. Timmermans PB: Pharmacological properties of angiotensin II receptor antagonists. Can J Cardiol. 1999 Nov;15 Suppl F:26F-8F. [PubMed:10579749]
External Links
Human Metabolome Database
HMDB0015437
PubChem Compound
60921
PubChem Substance
46508176
ChemSpider
54892
ChEMBL
CHEMBL305544
Therapeutic Targets Database
DAP001257
PharmGKB
PA164746338

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 Solubility0.0151 mg/mLALOGPS
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 Area120.22 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity137.15 m3·mol-1ChemAxon
Polarizability54.2 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.647
Caco-2 permeable-0.6148
P-glycoprotein substrateSubstrate0.5611
P-glycoprotein inhibitor INon-inhibitor0.6454
P-glycoprotein inhibitor IINon-inhibitor0.5279
Renal organic cation transporterNon-inhibitor0.8625
CYP450 2C9 substrateNon-substrate0.653
CYP450 2D6 substrateNon-substrate0.7866
CYP450 3A4 substrateSubstrate0.5105
CYP450 1A2 substrateNon-inhibitor0.6561
CYP450 2C9 inhibitorInhibitor0.6267
CYP450 2D6 inhibitorNon-inhibitor0.7996
CYP450 2C19 inhibitorInhibitor0.5274
CYP450 3A4 inhibitorNon-inhibitor0.5167
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8837
Ames testNon AMES toxic0.5853
CarcinogenicityNon-carcinogens0.6378
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.5781 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9673
hERG inhibition (predictor II)Inhibitor0.6568
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 2-arylbenzofuran flavonoids. These are phenylpropanoids containing the 2-phenylbenzofuran moiety.
Kingdom
Organic compounds
Super Class
Phenylpropanoids and polyketides
Class
2-arylbenzofuran flavonoids
Sub Class
Not Available
Direct Parent
2-arylbenzofuran flavonoids
Alternative Parents
2-phenylbenzofurans / Sulfanilides / 1,2,4,5-tetrasubstituted imidazoles / 2-heteroaryl carboxamides / Carbonylimidazoles / Organosulfonamides / Aryl bromides / Organic sulfonamides / N-substituted imidazoles / Aminosulfonyl compounds
show 14 more
Substituents
2-arylbenzofuran flavonoid / 2-phenylbenzofuran / Phenylbenzofuran / Sulfanilide / 1,2,4,5-tetrasubstituted imidazole / Benzofuran / 2-heteroaryl carboxamide / Imidazole-4-carbonyl group / Aryl bromide / Aryl halide
show 35 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. Timmermans PB: Pharmacological properties of angiotensin II receptor antagonists. Can J Cardiol. 1999 Nov;15 Suppl F:26F-8F. [PubMed:10579749]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Drug created on June 30, 2007 12:15 / Updated on August 02, 2018 07:59