Identification

Name
Forasartan
Accession Number
DB01342
Type
Small Molecule
Groups
Experimental
Description

Forasartan, a specific angiotensin II antagonist, is used alone or with other antihypertensive agents to treat hypertension. Forasartan competes with angiotensin II for binding at the AT1 receptor subtype. As angiotensin II is a vasoconstrictor which also stimulates the synthesis and release of aldosterone, blockage of its effects results in a decreases in systemic vascular resistance.

Structure
Thumb
Synonyms
  • forasartán
External IDs
SC-52458
Categories
UNII
065F7WPT0B
CAS number
145216-43-9
Weight
Average: 416.522
Monoisotopic: 416.243692936
Chemical Formula
C23H28N8
InChI Key
YONOBYIBNBCDSJ-UHFFFAOYSA-N
InChI
InChI=1S/C23H28N8/c1-3-5-11-21-25-22(12-6-4-2)31(28-21)16-17-13-14-20(24-15-17)18-9-7-8-10-19(18)23-26-29-30-27-23/h7-10,13-15H,3-6,11-12,16H2,1-2H3,(H,26,27,29,30)
IUPAC Name
5-[(dibutyl-1H-1,2,4-triazol-1-yl)methyl]-2-[2-(2H-1,2,3,4-tetrazol-5-yl)phenyl]pyridine
SMILES
CCCCC1=NN(CC2=CN=C(C=C2)C2=CC=CC=C2C2=NNN=N2)C(CCCC)=N1

Pharmacology

Indication

For the treatment of hypertension.

Pharmacodynamics

Forasartan, a specific angiotensin II antagonist, is used alone or with other antihypertensive agents to treat hypertension. By inhibiting angiotensin II receptors, this drug leads to a decrease in sodium reabsorption (which decreases water content of blood) and a decrease in vasoconstriction. Combined, this has the effect of lowering blood pressure.

Mechanism of action

Forasartan competes with angiotensin II for binding at the AT1 receptor subtype. As angiotensin II is a vasoconstrictor which also stimulates the synthesis and release of aldosterone, blockage of its effects results in a decreases in systemic vascular resistance. Also, since angiotensin causes vasoconstriction, the inhibition of this receptor decreases vasoconstriction, which consequently also decreases vascular resistnace.

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
PathwayCategory
Forasartan Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic AcidThe risk or severity of adverse effects can be increased when Forasartan is combined with 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid.
AcebutololThe risk or severity of hyperkalemia can be increased when Acebutolol is combined with Forasartan.
AceclofenacThe risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Forasartan is combined with Aceclofenac.
AcemetacinThe risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Forasartan is combined with Acemetacin.
Acetylsalicylic acidThe risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Forasartan is combined with Acetylsalicylic acid.
AgmatineThe risk or severity of hyperkalemia can be increased when Forasartan is combined with Agmatine.
AlclofenacThe risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Forasartan is combined with Alclofenac.
AliskirenThe risk or severity of hyperkalemia can be increased when Aliskiren is combined with Forasartan.
AlminoprofenThe risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Forasartan is combined with Alminoprofen.
AlogliptinThe risk or severity of angioedema can be increased when Forasartan is combined with Alogliptin.
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0015434
KEGG Drug
D04243
PubChem Compound
132706
PubChem Substance
46505698
ChemSpider
117146
BindingDB
50049209
ChEBI
141552
ChEMBL
CHEMBL315021
Therapeutic Targets Database
DAP001256
PharmGKB
PA164776845
Wikipedia
Forasartan

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 Solubility0.00667 mg/mLALOGPS
logP4.51ALOGPS
logP5.89ChemAxon
logS-4.8ALOGPS
pKa (Strongest Acidic)7.35ChemAxon
pKa (Strongest Basic)3.99ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area98.06 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity145.44 m3·mol-1ChemAxon
Polarizability46.79 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9069
Caco-2 permeable+0.5
P-glycoprotein substrateSubstrate0.615
P-glycoprotein inhibitor INon-inhibitor0.6612
P-glycoprotein inhibitor IINon-inhibitor0.8805
Renal organic cation transporterInhibitor0.5228
CYP450 2C9 substrateNon-substrate0.7854
CYP450 2D6 substrateNon-substrate0.831
CYP450 3A4 substrateNon-substrate0.5512
CYP450 1A2 substrateNon-inhibitor0.64
CYP450 2C9 inhibitorNon-inhibitor0.5115
CYP450 2D6 inhibitorNon-inhibitor0.7168
CYP450 2C19 inhibitorInhibitor0.7661
CYP450 3A4 inhibitorInhibitor0.6576
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7192
Ames testNon AMES toxic0.5233
CarcinogenicityNon-carcinogens0.8243
BiodegradationNot ready biodegradable0.9969
Rat acute toxicity2.7970 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.6462
hERG inhibition (predictor II)Non-inhibitor0.546
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 phenylpyridines. These are polycyclic aromatic compounds containing a benzene ring linked to a pyridine ring through a CC or CN bond.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Pyridines and derivatives
Sub Class
Phenylpyridines
Direct Parent
Phenylpyridines
Alternative Parents
Phenyltetrazoles and derivatives / Benzene and substituted derivatives / Triazoles / Heteroaromatic compounds / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Hydrocarbon derivatives
Substituents
2-phenylpyridine / Phenyltetrazole / Benzenoid / Monocyclic benzene moiety / Heteroaromatic compound / 1,2,4-triazole / Tetrazole / Azole / Azacycle / Organic nitrogen compound
Molecular Framework
Aromatic heteromonocyclic 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. Tokunaga R, Kushiku K, Yamada K, Yamada H, Furukawa T: Possible involvement of calcium-calmodulin pathways in the positive chronotropic response to angiotensin II on the canine cardiac sympathetic ganglia. Jpn J Pharmacol. 2001 Aug;86(4):381-9. [PubMed:11569611]
  2. Usune S, Furukawa T: Effects of SC-52458, a new nonpeptide angiotensin II receptor antagonist, on increase in cytoplasmic Ca2+ concentrations and contraction induced by angiotensin II and K(+)-depolarization in guinea-pig taenia coli. Gen Pharmacol. 1996 Oct;27(7):1179-85. [PubMed:8981065]
  3. Hagmann M, Nussberger J, Naudin RB, Burns TS, Karim A, Waeber B, Brunner HR: SC-52458, an orally active angiotensin II-receptor antagonist: inhibition of blood pressure response to angiotensin II challenges and pharmacokinetics in normal volunteers. J Cardiovasc Pharmacol. 1997 Apr;29(4):444-50. [PubMed:9156352]
  4. 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 12:11 / Updated on November 02, 2018 05:00