Fimasartan

Targets (1)Transporters (2)Biointeractions (3)

Identification

Name
Fimasartan
Accession Number
DB09279
Type
Small Molecule
Groups
Investigational
Description

Fimasartan is a non-peptide angiotensin II receptor antagonist (ARB) used for the treatment of hypertension and heart failure. Concurrent administration of fimasartan with diuretic hydrochlorothiazide has shown to be safe in clinical trials. Fimasartan was approved for use in South Korea in September 9th, 2010 and is available under the brand name Kanarb through Boryung Pharmaceuticals, who are presently seeking worldwide partnership.

Structure
Thumb
3D
Similar Structures
Synonyms
Not Available
Product Ingredients
IngredientUNIICASInChI Key
Fimasartan potassium trihydrate4516BN0T4B1020110-23-9IJEKJHQBGZFMMI-UHFFFAOYSA-N
International/Other Brands
Kanarb (Boryung Pharmaceuticals)
Categories
UNII
P58222188P
CAS number
247257-48-3
Weight
Average: 501.65
Monoisotopic: 501.23107982
Chemical Formula
C27H31N7OS
InChI Key
AMEROGPZOLAFBN-UHFFFAOYSA-N
InChI
InChI=1S/C27H31N7OS/c1-5-6-11-24-28-18(2)23(16-25(36)33(3)4)27(35)34(24)17-19-12-14-20(15-13-19)21-9-7-8-10-22(21)26-29-31-32-30-26/h7-10,12-15H,5-6,11,16-17H2,1-4H3,(H,29,30,31,32)
IUPAC Name
2-(2-butyl-4-methyl-6-oxo-1-{[2'-(1H-1,2,3,4-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl]methyl}-1,6-dihydropyrimidin-5-yl)-N,N-dimethylethanethioamide
SMILES
CCCCC1=NC(C)=C(CC(=S)N(C)C)C(=O)N1CC1=CC=C(C=C1)C1=C(C=CC=C1)C1=NN=NN1

Pharmacology

Indication

Used for the treatment of hypertension and heart failure [1].

Pharmacodynamics

Fimasartan is a selective angiotensin receptor 1 (AR1) inhibitor [1]. It acts to lower blood pressure by inhibiting vasoconstriction

Mechanism of action

Angiotensin II activates AR1 leading to vasoconstriction and increased noradrenaline release which further increases vasoconstriction via action at α1-adrenergic receptors [1, 2]. It also stimulates secretion of aldosterone which acts to increase sodium and water reabsorption in the renal tubules [2]. Fimasartan bind to and antagonizes AR1 preventing vasoconstriction and reducing aldosterone secretion to increase natriuresis leading to a reduction in blood volume. Together these effects produce an anti-hypertensive effect.

TargetActionsOrganism
AType-1 angiotensin II receptor
antagonist
Humans
Absorption

Tmax is 0.5-1.3 h [1].

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination

Most is eliminated unchangd in bile with less than 3% in the urine [1].

Half life

The half life of elimination is 7-10 h [1].

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
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 Fimasartan is combined with 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid.
AbemaciclibAbemaciclib may decrease the excretion rate of Fimasartan which could result in a higher serum level.
AcebutololThe risk or severity of hyperkalemia can be increased when Acebutolol is combined with Fimasartan.
AceclofenacThe risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Fimasartan is combined with Aceclofenac.
AcemetacinThe risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Fimasartan is combined with Acemetacin.
AcetylcysteineThe excretion of Fimasartan can be decreased when combined with Acetylcysteine.
Acetylsalicylic acidThe risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Fimasartan is combined with Acetylsalicylic acid.
AfatinibAfatinib may decrease the excretion rate of Fimasartan which could result in a higher serum level.
AgmatineThe risk or severity of hyperkalemia can be increased when Agmatine is combined with Fimasartan.
AlclofenacThe risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Fimasartan is combined with Alclofenac.
Food Interactions
Not Available

References

General References
  1. Kim JH, Lee JH, Paik SH, Kim JH, Chi YH: Fimasartan, a novel angiotensin II receptor antagonist. Arch Pharm Res. 2012 Jul;35(7):1123-6. doi: 10.1007/s12272-012-0700-z. [PubMed:22864732]
  2. Rang, H. P. and Dale, M. M. (2012). Rang and Dale's Pharmacology (7th ed.). Edinburgh: Elsevier/Churchill Livingstone. [ISBN:978-0-7020-3471-8]
External Links
PubChem Compound
9870652
PubChem Substance
310265172
ChemSpider
8046343
BindingDB
50364573
ChEBI
136044
ChEMBL
CHEMBL1951143
Wikipedia
Fimasartan
ATC Codes
C09CA10 — Fimasartan

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableHealthy Volunteers2
1CompletedNot AvailableHepatic Impairment / Hypertension,Essential1
1CompletedNot AvailableHigh Blood Pressure (Hypertension)5
1CompletedNot AvailableHypertension,Essential8
1CompletedNot AvailableImpaired Renal Function1
1CompletedOtherHigh Blood Pressure (Hypertension)2
1CompletedTreatmentHigh Blood Pressure (Hypertension) / Hyperlipidemias2
1CompletedTreatmentHypertension, Hyperlipidemia1
1CompletedTreatmentHypertension,Essential1
1RecruitingOtherDiabetes Mellitus (DM) / High Blood Pressure (Hypertension)1
2CompletedTreatmentHigh Blood Pressure (Hypertension)3
2CompletedTreatmentHypertension,Essential2
3CompletedTreatmentArterial Hypertension1
3CompletedTreatmentEssential Hypertension, Dyslipidemia1
3CompletedTreatmentHigh Blood Pressure (Hypertension)3
3CompletedTreatmentHypertension,Essential3
3RecruitingTreatmentChronic Kidney Disease (CKD)1
3RecruitingTreatmentDyslipidemias / Hypertension,Essential1
3RecruitingTreatmentEssential Hypertension, Dyslipidemia1
4Active Not RecruitingTreatmentBlood Pressures / Stroke, Ischemic1
4Active Not RecruitingTreatmentHigh Blood Pressure (Hypertension)1
4CompletedTreatmentEssential,Hypertension1
4CompletedTreatmentHigh Blood Pressure (Hypertension)2
4TerminatedTreatmentCoronary Artery Disease1
4Unknown StatusTreatmentCritical Stenosis of Aortic Valve1
Not AvailableActive Not RecruitingNot AvailableHigh Blood Pressure (Hypertension)1
Not AvailableCompletedTreatmentDiabetes Mellitus (DM) / High Blood Pressure (Hypertension)1

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 Solubility0.00469 mg/mLALOGPS
logP4.09ALOGPS
logP4.21ChemAxon
logS-5ALOGPS
pKa (Strongest Acidic)4.23ChemAxon
pKa (Strongest Basic)1.34ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area90.37 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity161.24 m3·mol-1ChemAxon
Polarizability54.86 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
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 biphenyls and derivatives. These are organic compounds containing to benzene rings linked together by a C-C bond.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Biphenyls and derivatives
Direct Parent
Biphenyls and derivatives
Alternative Parents
Phenyltetrazoles and derivatives / Pyrimidones / Hydropyrimidines / Thioamides / Heteroaromatic compounds / Lactams / Thiocarboxylic acid amides / Azacyclic compounds / Thiocarbonyl compounds / Organopnictogen compounds
show 4 more
Substituents
Biphenyl / Phenyltetrazole / Pyrimidone / Hydropyrimidine / Pyrimidine / Azole / Heteroaromatic compound / Tetrazole / Thioamide / Lactam
show 13 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available

Targets

Details1. Type-1 angiotensin II receptor
Kind
Protein
Organism
Humans
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. Kim JH, Lee JH, Paik SH, Kim JH, Chi YH: Fimasartan, a novel angiotensin II receptor antagonist. Arch Pharm Res. 2012 Jul;35(7):1123-6. doi: 10.1007/s12272-012-0700-z. [PubMed:22864732]

Transporters

Details1. Solute carrier organic anion transporter family member 1B1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. Choi Y, Lee S, Jang IJ, Yu KS: Pharmacokinetic interaction between fimasartan and atorvastatin in healthy male volunteers. Drug Des Devel Ther. 2018 Jul 24;12:2301-2309. doi: 10.2147/DDDT.S165171. eCollection 2018. [PubMed:30087555]
Details2. ATP-binding cassette sub-family G member 2
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
References
  1. Choi Y, Lee S, Jang IJ, Yu KS: Pharmacokinetic interaction between fimasartan and atorvastatin in healthy male volunteers. Drug Des Devel Ther. 2018 Jul 24;12:2301-2309. doi: 10.2147/DDDT.S165171. eCollection 2018. [PubMed:30087555]

Drug created on October 29, 2015 09:04 / Updated on December 30, 2018 07:59