CAS 137862-53-4|valsartan|Valsarran|Diovan|(2S)-3-methyl-2-[N-({4-[2-(2H-1,2,3,4-tetrazol-5-yl)phenyl]phenyl}methyl)pentanamido]butanoic acid|Valsartan|Diovan|valsartan|(S)-2-(N-((2'-(1H-Tetrazol-5-...

General Information

Structure

Molecular Formula

C₂₄H₂₉N₅O₃

Molecular Mass

435.51876

Exact Mass

435.22703981

Charge

0

InChI

InChI=1S/C24H29N5O3/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,(H,31,32)(H,25,26,27,28)/t22-/m0/s1

InChIKey

ACWBQPMHZXGDFX-QFIPXVFZSA-N

Canonic Smiles

CCCCC(=O)N([C@H](C(=O)O)C(C)C)Cc1ccc(cc1)c1ccccc1c1n[nH]nn1

Isomeric Smiles

OC(=O)[C@@H](N(Cc1ccc(cc1)c1c(cccc1)c1n[nH]nn1)C(=O)CCCC)C(C)C

Calculated Properties

JChem

LogD (pH = 7.4)

0.08

LogD (pH = 5.5)

2.31

Log P

4.59

Rotatable Bonds

10

H Donor

2

H Acceptors

6

Lipinski's Rule of Five

true

Acid pKa

4.00

Polar Surface Area

112.07

Polarizability

46.44

Molar Refractivity

134.77

LOG S

-6.95

Data Source

Academic Data

Commercial Catalog

Data Source

Names and Identifiers

Synonyms

valsartanValsartanDiovan(S)-2-(N-((2'-(1H-Tetrazol-5-yl)-[1,1'-biphenyl]-4-yl)methyl)pentanamido)-3-methylbutanoic acidN-(1-Oxopentyl)-N-[[2′-(2H-tetrazol-5-yl)[1,1′-biphenyl]-4-yl]methyl]-L-valineValsartanL-ValsartanValtanvalsartanDiovanN-(p-(o-1H-tetrazol-5-ylphenyl)benzyl)-N-valeryl-L-valine(S)-N-valeryl-N-{[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]-methyl}-valineN-pentanoyl-N-{[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-L-valine

Brand Name

ValsarranDiovan

IUPAC name

(2S)-3-methyl-2-[N-({4-[2-(2H-1,2,3,4-tetrazol-5-yl)phenyl]phenyl}methyl)pentanamido]butanoic acid (2S)-3-methyl-2-[N-({4-[2-(1H-1,2,3,4-tetrazol-5-yl)phenyl]phenyl}methyl)pentanamido]butanoic acid (2S)-3-methyl-2-(N-{[2'-(1H-1,2,3,4-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl]methyl}pentanamido)butanoic acid

IUPAC Traditional name

valsartan diovan (2S)-3-methyl-2-[N-({4-[2-(1H-1,2,3,4-tetrazol-5-yl)phenyl]phenyl}methyl)pentanamido]butanoic acid

API Name

VALSARTAN

International Nonproprietary Name (INN)

valsartan

Names and Identifiers

Registration numbers

MDL Number

MFCD00865840

CAS Number

137862-53-4

PubChem CID

60846

PubChem SID

1609635254650900046530915

DrugBank ID

DB00177

Patent number

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

LINCS Database

LSM-2993

MetaboLights Database

MTBLS204MTBLS2633MTBLS136MTBLS407MTBLS1455MTBLS220

Reaxys Registry

CHEBI ID

Protein Data Bank

Wikipedia Title

HMDB Database

Drug Central Database

KEGG DRUG Database

BindingDB Database

CHEMBL

SureChEMBL Database

Reactom Database

R-HSA-9615249R-HSA-374173

Beilstein Number

7754038

Registration numbers

Properties

Physical Property

Hydrophobicity(logP)

5.8

Apperance

white to tan powder

Solubility

DMSO: ≥20 mg/mL

Optical Rotation

[α]/D -55 to -70°, c = 1 in methanol

Product Information

Purity

95+%

≥98% (HPLC)

Salt Data

Free Base

Empirical Formula (Hill Notation)

C24H29N5O3

Application(s)

Antihypertensive agent

Pharmacology Properties

Target

Angiotensin recep

Mechanism of Action

Angiotensin 2 receptor antagonist

Properties

Related Proteins

PDB Bank

7BM1

Related Proteins

Molecular Spectra

No Data Available

Click here to submit data

Molecule Details

DrugBank

DB00177

Drug Groups

approved; investigational

Description

Valsartan is an angiotensin-receptor blocker (ARB) that may be used to treat a variety of cardiac conditions including hypertension, diabetic nephropathy and heart failure. Valsartan lowers blood pressure by antagonizing the renin-angiotensin-aldosterone system (RAAS); it competes with angiotensin II for binding to the type-1 angiotensin II receptor (AT1) subtype and prevents the blood pressure increasing effects of angiotensin II. Unlike angiotensin-converting enzyme (ACE) inhibitors, ARBs do not have the adverse effect of dry cough. Valsartan may be used to treat hypertension, isolated systolic hypertension, left ventricular hypertrophy and diabetic nephropathy. It may also be used as an alternative agent for the treatment of heart failure, systolic dysfunction, myocardial infarction and coronary artery disease.

Indication

May be used as a first line agent to treat uncomplicated hypertension, isolated systolic hypertension and left ventricular hypertrophy. May be used as a first line agent to delay progression of diabetic nephropathy. Losartan may be also used as a second line agent in the treatment of congestive heart failure, systolic dysfunction, myocardial infarction and coronary artery disease in those intolerant of ACE inhibitors.

Pharmacology

Valsartan belongs to a class of antihypertensive agents called angiotensin II receptor blockers (ARBs). Valsartan is a specific and selective type-1 angiotensin II receptor (AT1) antagonist which blocks the blood pressure increasing effects angiotensin II via the renin-angiotensin-aldosterone system (RAAS). RAAS is a homeostatic mechanism for regulating hemodynamics, water and electrolyte balance. During sympathetic stimulation or when renal blood pressure or blood flow is reduced, renin is released from granular cells of the juxtaglomerular apparatus in the kidneys. Renin cleaves circulating angiotensinogen to angiotensin I, which is cleaved by angiotensin converting enzyme (ACE) to angiotensin II. Angiotensin II increases blood pressure by increasing total peripheral resistance, increasing sodium and water reabsorption in the kidneys via aldosterone secretion, and altering cardiovascular structure. Angiotensin II binds to two receptors: AT1 and type-2 angiotensin II receptor (AT2). AT1 is a G-protein coupled receptor (GPCR) that mediates the vasoconstrictive and aldosterone-secreting effects of angiotensin II. Studies performed in recent years suggest that AT2 antagonizes AT1-mediated effects and directly affects long-term blood pressure control by inducing vasorelaxation and increasing urinary sodium excretion. Angiotensin receptor blockers (ARBs) are non-peptide competitive inhibitors of AT1. ARBs block the ability of angiotensin II to stimulate pressor and cell proliferative effects. Unlike ACE inhibitors, ARBs do not affect bradykinin-induced vasodilation. The overall effect of ARBs is a decrease in blood pressure.

Affected Organisms

Humans and other mammals

Biotransformation

Valsartan is excreted largely as unchanged drug (80%) and is minimally metabolized in humans. The primary circulating metabolite, 4-OH-valsartan, is pharmacologically inactive and produced CYP2C9. 4-OH-valsartan accounts for approximately 9% of the circulating dose of valsartan. Although valsartan is metabolized by CYP2C9, CYP-mediated drug-drug interactions between valsartan and other drugs is unlikely.

Absorption

Absolute bioavailability = 23% with high variability

Half Life

The initial phase t_{1/2 α} is < 1 hour while the terminal phase t_{1/2 β} is 5-9 hours.

Protein Binding

94 - 97% bound to serum proteins, primarily serum albumin

Elimination

83% of absorbed valsartan is excreted in feces and 13% is excreted in urine, primarily as unchanged drug

Distribution

* 17 L (low tissue distribution)

Clearance

* 2 L/h [IV administration]
* 4.5 L/h [heart Failure patients receiving oral administration 40 to 160 mg twice a day]

References

• Bader, M. (2004). Renin-angiotensin-aldosterone system. In S. Offermanns, & W. Rosenthal (Eds.). _Encyclopedic reference of molecular pharmacology_ (pp. 810-814). Berlin, Germany: Springer.

• Diovan. (2009). [Electronic version]. e-CPS. Retrieved December 28, 2009.

• Stanfield, C.L., & Germann, W.J. (2008). _Principles of human physiology_ (3 ^rd^ ed.). San Francisco, CA: Pearson Education, Inc.

External Links

• [Wikipedia]

• [RxList]

• [Drugs.com]

Selleck Chemicals

S1894

Research Area: Cardiovascular Disease
Biological Activity:
Valsartan (Diovan) is an angiotensin II receptor antagonist with IC50 of ranging from 39.5 to116 µM. By blocking the action of angiotensin, valsartan dilates blood vessels and reduces blood pressure. In the Value trial, the angiotensin II receptor blocker valsartan produced a statistically significant 19% (p=0.02) relative increase in the prespecified secondary end point of myocardial infarction (fatal and non-fatal) compared with amlodipine. The CHARM-alternative trial showed a significant +52% (p=0.025) increase in myocardial infarction with candesartan (versus placebo) despite a reduction in blood pressure. [1]

ChEBI

CHEBI:9927

A monocarboxylic acid amide consisting of L-valine in which the amino hydrogens have been replaced by a pentanoyl and a [2'-(1H-tetrazol-5-yl)biphenyl]-4-yl]methyl group. It exhibits antihypertensive activity.

Molecule Details

References

PubChem Literature

From Data Sources

• Stanfield, C.L., & Germann, W.J. (2008). _Principles of human physiology_ (3 ^rd^ ed.). San Francisco, CA: Pearson Education, Inc.

• Bader, M. (2004). Renin-angiotensin-aldosterone system. In S. Offermanns, & W. Rosenthal (Eds.). _Encyclopedic reference of molecular pharmacology_ (pp. 810-814). Berlin, Germany: Springer.

• Diovan. (2009). [Electronic version]. e-CPS. Retrieved December 28, 2009.

• http://en.wikipedia.org/wiki/Valsartan

• Buhlmayer, P. et al., Bioorg. Med. Chem. Lett., 1994, 4, 29, (synth)

• Langley, H.D. et al., Drugs, 1999, 57, 751-755, (rev)

• Martindale, The Extra Pharmacopoeia, 32nd edn., Pharmaceutical Press, 1999, 960

• Criscione, L. et al., Br. J. Pharmacol., 1993, 110, 761, (pharmacol)

• Wood, J.M. et al., Hypertension (Dallas), 1993, 21, 1056, (pharmacol)

• Eur. Pat., 1991, Ciba-Geigy, 443 983; CA, 116, 151772t, (synth, pharmacol)

• Markham, A. et al., Drugs, 1997, 54, 299-311, (rev)

References

Bioactivity

PubChem BioAssay

Bioactivity

Molecule

ID:62