Valsartan Disodium

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C24H27N5O3.2Na
Molecular Weight	479.4824
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[Na+].[Na+].CCCCC(=O)N(CC1=CC=C(C=C1)C2=CC=CC=C2C3=NN=N[N-]3)[C@@H](C(C)C)C([O-])=O

InChI

InChIKey=SJSMGDIQKOTNND-IKXQUJFKSA-L

InChI=1S/C24H29N5O3.2Na/c1-4-5-10-21(30)29(22(16(2)3)24(31)32)15-17-11-13-18(14-12-17)19-8-6-7-9-20(19)23-25-27-28-26-23;;/h6-9,11-14,16,22H,4-5,10,15H2,1-3H3,(H2,25,26,27,28,31,32);;/q;2*+1/p-2/t22-;;/m0../s1

HIDE SMILES / InChI

Description
Sources: https://www.pharma.us.novartis.com/sites/www.pharma.us.novartis.com/files/entresto.pdfhttp://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021283s50lbl.pdfhttps://www.ncbi.nlm.nih.gov/pubmed/25052956
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/mesh/2009869

There is no information in the literature about pharmacological and biological application of definite isomer of valsatran, R – form (also known as VALSARTAN, D- or CGP-49309). However there were found, that in the tablets of valsartan, which are used to treat high blood pressure and to heart failure, the R-enantiomer was an impurity.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Type-1 angiotensin II receptor 41 Target ID: CHEMBL227 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207620Orig1s000PharmR.pdf	Antagonist 2849	2.38 nM [Ki]
Neprilysin 29 Target ID: CHEMBL1944 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207620Orig1s000PharmR.pdf	Inhibitor 8504	2.3 nM [IC50]
Type-1 angiotensin II receptor 41 Target ID: CHEMBL227 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021283s50lbl.pdf	Blocker 555	2.43 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Unknown 2596
Chronic heart failure with reduced ejection fraction 4 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207620Orig1s000lbl.pdf	Primary	Approved 8583	ENTRESTO Approved Use ENTRESTO is a combination of sacubitril, a neprilysin inhibitor, and valsartan, an angiotensin II receptor blocker, indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction. ENTRESTO is usually administered in conjunction with other heart failure therapies, in place of an ACE inhibitor or other ARB. Launch Date 2015
Hypertension 575 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021283s50lbl.pdf	Primary	Approved 8583	DIOVAN Approved Use Diovan is an angiotensin II receptor blocker (ARB) indicated for: Treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions (1.1) Treatment of heart failure (NYHA class II-IV); Diovan significantly reduced hospitalization for heart failure (1.2) Reduction of cardiovascular mortality in clinically stable patients with left ventricular failure or left ventricular dysfunction following myocardial infarction (1.3) Launch Date 2011
Heart failure 106 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021283s50lbl.pdf	Primary	Approved 8583	DIOVAN Approved Use Diovan is an angiotensin II receptor blocker (ARB) indicated for: Treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions (1.1) Treatment of heart failure (NYHA class II-IV); Diovan significantly reduced hospitalization for heart failure (1.2) Reduction of cardiovascular mortality in clinically stable patients with left ventricular failure or left ventricular dysfunction following myocardial infarction (1.3) Launch Date 2011
Myocardial infarction 125 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021283s50lbl.pdf	Palliative	Approved 8583	DIOVAN Approved Use Diovan is an angiotensin II receptor blocker (ARB) indicated for: Treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions (1.1) Treatment of heart failure (NYHA class II-IV); Diovan significantly reduced hospitalization for heart failure (1.2) Reduction of cardiovascular mortality in clinically stable patients with left ventricular failure or left ventricular dysfunction following myocardial infarction (1.3) Launch Date 2011

C_max

Value	Dose	Analyte	Population
2.141 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21617777	160 mg single, oral dose: 160 mg route of administration: Oral experiment type: SINGLE co-administered:	VALSARTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
2808 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27128457	80 mg single, oral dose: 80 mg route of administration: Oral experiment type: SINGLE co-administered:	VALSARTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
5756 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27128457	80 mg single, oral dose: 80 mg route of administration: Oral experiment type: SINGLE co-administered:	VALSARTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
22.56 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21617777	160 mg single, oral dose: 160 mg route of administration: Oral experiment type: SINGLE co-administered:	VALSARTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
20650 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27128457	80 mg single, oral dose: 80 mg route of administration: Oral experiment type: SINGLE co-administered:	VALSARTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
34310 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27128457	80 mg single, oral dose: 80 mg route of administration: Oral experiment type: SINGLE co-administered:	VALSARTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
9.55 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21617777	160 mg single, oral dose: 160 mg route of administration: Oral experiment type: SINGLE co-administered:	VALSARTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
8.45 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27128457	80 mg single, oral dose: 80 mg route of administration: Oral experiment type: SINGLE co-administered:	VALSARTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27128457	80 mg single, oral dose: 80 mg route of administration: Oral experiment type: SINGLE co-administered:	VALSARTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:9927	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:9927
ChemicalBook	CB14657818	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB14657818
ChemicalBook	CB23133442	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB23133442
ChemicalBook	CB34813436	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB34813436
ChemicalBook	CB3952405	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB3952405
ChemicalBook	CB6182539	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB6182539
eMolecules	1989469	https://www.emolecules.com/cgi-bin/more?vid=1989469
eMolecules	2724803	https://www.emolecules.com/cgi-bin/more?vid=2724803
eMolecules	32278148	https://www.emolecules.com/cgi-bin/more?vid=32278148
eMolecules	33507560	https://www.emolecules.com/cgi-bin/more?vid=33507560
MolPort	MolPort-002-507-854	https://www.molport.com/shop/molecule-link/MolPort-002-507-854
MolPort	MolPort-003-666-608	https://www.molport.com/shop/molecule-link/MolPort-003-666-608
Selleck Chemicals	Valsartan(Diovan)	http://www.selleckchem.com/products/Valsartan(Diovan).html
ZINC	ZINC000003875259	http://zinc15.docking.org/substances/ZINC000003875259

PubMed

Title	Date	PubMed
Pharmacodynamic and Pharmacokinetic Profiles of Sacubitril/Valsartan (LCZ696) in Patients with Heart Failure and Reduced Ejection Fraction.	2016-08	26990595
LCZ696, an angiotensin receptor-neprilysin inhibitor, improves cardiac function with the attenuation of fibrosis in heart failure with reduced ejection fraction in streptozotocin-induced diabetic mice.	2016-04	26749570
Influence of Ejection Fraction on Outcomes and Efficacy of Sacubitril/Valsartan (LCZ696) in Heart Failure with Reduced Ejection Fraction: The Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) Trial.	2016-03	26915374
LCZ696 (Valsartan/Sacubitril)--A Possible New Treatment for Hypertension and Heart Failure.	2016-01	26280447
Sacubitril/valsartan (LCZ696) for the treatment of heart failure.	2016	26642078
LCZ696 : a new paradigm for the treatment of heart failure?	2015-02	25597387
Determination of the R-enantiomer of valsartan in pharmaceutical formulation by capillary electrophoresis.	2015	25052956
Efficacy and safety of LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor, in Asian patients with hypertension: a randomized, double-blind, placebo-controlled study.	2014-04	24446062
Enantiomeric LC separation of valsartan on amylose based stationary phase.	2009-08	19746836
Development and validation of chiral high-performance liquid chromatographic methods for the quantitation of valsartan and of the tosylate of valinebenzyl ester.	1996-11-08	8953194
Valsartan, a new angiotensin II antagonist for the treatment of essential hypertension: a comparative study of the efficacy and safety against amlodipine.	1996-09	8841157
Remodelling of resistance arteries in genetically hypertensive rats by treatment with valsartan, an angiotensin II receptor antagonist.	1996-06-01	8800589
Binding of valsartan to mammalian angiotensin AT1 receptors.	1995-11-10	8577935
Angiotensin II receptor blockade with single doses of valsartan in healthy, normotensive subjects.	1994	7867676
Pharmacological profile of valsartan: a potent, orally active, nonpeptide antagonist of the angiotensin II AT1-receptor subtype.	1993-10	8242249

Patents

Sample Use Guides

In Vivo Use Guide

The recommended starting dose of ENTRESTO, previously known as LCZ696, is 49/51 mg (sacubitril/valsartan) twice-daily. Double the dose of ENTRESTO after 2 to 4 weeks to the target maintenance dose of 97/103 mg (sacubitril/valsartan) twice-daily, as tolerated by the patient.

Route of Administration: Oral

In Vitro Use Guide

30 nM to 1 uM valsartan (LCZ696 component) in the presence of 10 uM LBQ657 (Sacubitril (LCZ696 component) metabolite) demonstrate anti-fibrotic and anti-hypertrophic effects on rat cardiac fibroblasts and cardiomyocytes, respectively, cultured with 100 nM angiotensin II

Name

Type

Language

L-VALINE, N-(1-OXOPENTYL)-N-((2'-(2H-TETRAZOL-5-YL)(1,1'-BIPHENYL)-4-YL)METHYL)-, SODIUM SALT (1:2)

Preferred Name

English

Valsartan Disodium

Common Name

English

Code System Code Type Description

FDA UNII

U55M6YDH5T