CAS 141505-33-1|1-cyano-N-{4-[(4R)-4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl]phenyl}methanecarbohydrazonoyl cyanide|levosimendan|Levosimendan|(-)-OR-1259|2-[2-[4-[(4R)-1,4,5,6-Tetrahydro-4-met...

General Information

Structure

Molecular Formula

C₁₄H₁₂N₆O

Molecular Mass

280.28468

Exact Mass

280.10725903

Charge

InChI

InChI=1S/C14H12N6O/c1-9-6-13(21)19-20-14(9)10-2-4-11(5-3-10)17-18-12(7-15)8-16/h2-5,9,17H,6H2,1H3,(H,19,21)/t9-/m1/s1

InChIKey

WHXMKTBCFHIYNQ-SECBINFHSA-N

Canonic Smiles

N#CC(=NNc1ccc(cc1)C1=NNC(=O)C[C@H]1C)C#N

Isomeric Smiles

O=C1NN=C([C@@H](C1)C)c1ccc(NN=C(C#N)C#N)cc1

Calculated Properties

JChem

Acid pKa

10.534338

H Acceptors

H Donor

LogD (pH = 5.5)

2.0628319

LogD (pH = 7.4)

2.159906

Log P

2.1616182

Molar Refractivity

77.6308

Polarizability

27.841526

Polar Surface Area

113.43

Rotatable Bonds

Lipinski's Rule of Five

true

ALOGPS 2.1

Log P

2.69

LOG S

-3.5

Solubility (Water)

8.81e-02 g/l

Data Source

Academic Data

Commercial Catalog

Data Source

Names and Identifiers

Synonyms

(-)-OR-1259R)-((4-(1,4,5,6-Tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl)hydrazono) propanedintrile(R)-Simendan2-[2-[4-[(4R)-1,4,5,6-Tetrahydro-4-methyl-6-oxo-3-pyridazinyl]phenyl]hydrazinylidene]-propanedinitrileOR 1259LevosimendanSimdaxLevosimendan[[4-[(4R)-1,4,5,6-Terahydro-4-methyl-6-oxo-3-pyridazinyl]phenyl]hydrazono]propanedinitrileOR-1259Levosimedan

IUPAC name

1-cyano-N-{4-[(4R)-4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl]phenyl}methanecarbohydrazonoyl cyanide

IUPAC Traditional name

levosimendan

Brand Name

SimdaxSimendan

Names and Identifiers

Registration numbers

PubChem SID

CAS Number

PubChem CID

MDL Number

Registration numbers

Properties

Product Information

Empirical Formula (Hill Notation)

C14H12N6O

Purity

≥98% (HPLC)

Certificate of Analysis

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Physical Property

Properties

Related Proteins

No Data Available

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Molecular Spectra

No Data Available

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Molecule Details

DrugBank

DB00922

Drug Groups

approved; investigational

Description

Levosimendan is a calcium sensitiser used in the management of acutely decompensated congestive heart failure. It increases the sensitivity of the heart to calcium, thus increasing cardiac contractility without a rise in intracellular calcium. Levosimendan exerts its effect by increasing calcium sensitivity of myocytes by binding to cardiac troponin C in a calcium-dependent manner. It also has a vasodilatory effect, by opening adenosine triphosphate (ATP)-sensitive potassium channels in vascular smooth muscle to cause smooth muscle relaxation.

Indication

For short term treatment of acutely decompensated severe chronic heart failure (CHF). Also being investigated for use/treatment in heart disease.

Pharmacology

Levosimendan is a new Ca²⁺-sensitizing inotropic agent. Ca²⁺ sensitizers represent a new class of inotropic agents, which overcome the disadvantages associated with currently available inotropic agents in as they are not associated with an increased risk of arrhythmias, cell injury and death due to Ca²⁺ overload in myocardial cells; they do not increase the activation energy; and they have the potential to reverse contractile dysfunction under pathophysiologic conditions, such as acidosis or myocardial stunning. Levosimendan has not been approved for use in the U.S. or Canada.

Affected Organisms

Humans and other mammals

Biotransformation

Complete metabolism, with some active metabolites (OR-1855 and OR-1896) possibly extending the drug's haemodynamic effects.

Absorption

The bioavailability of oral levosimendan is 85 ± 6% in healthy volunteers and 84 ± 4% in patients.

Half Life

Eliminination half-life is approximately 1 hour.

Protein Binding

98% bound to plasma protein.

References

• [Link]

• Mebazaa A, Nieminen MS, Packer M, Cohen-Solal A, Kleber FX, Pocock SJ, Thakkar R, Padley RJ, Poder P, Kivikko M: Levosimendan vs dobutamine for patients with acute decompensated heart failure: the SURVIVE Randomized Trial. JAMA. 2007 May 2;297(17):1883-91. [Pubmed]

• Kasikcioglu HA, Cam N: A review of levosimendan in the treatment of heart failure. Vasc Health Risk Manag. 2006;2(4):389-400. [Pubmed]

External Links

• [Wikipedia]

Sigma Aldrich

L5545

Biochem/physiol Actions
Levosimendan is a calcium sensitiser. The compound increases the sensitivity of the heart to calcium, thus increasing cardiac contractility without a rise in intracellular calcium. Levosimendan binds to cardiac troponin C in a calcium-dependent manner and stabilizes troponin C. This is followed by actin-myosin cross-bridges, without increasing myocardial consumption of ATP. Additionally the compound acts as vasodilator by opening an ATP-sensitive potassium channels. Levosimendan is a drug used for treatment of congestive heart failure. Also it can be used to treat calcium channel blocker overdose.

TRC

L378000

Bioactive enantiomer of racemate, Simendan. Positive inotropic agent with vasodilating activity. Cardiotonic.

Molecule Details

References

PubChem Literature

From Data Sources

• Link

• Kasikcioglu HA, Cam N: A review of levosimendan in the treatment of heart failure. Vasc Health Risk Manag. 2006;2(4):389-400. Pubmed

• Pagel, P.S., et al.: Cardiovasc. Drug Rev., 14, 286 (1995)

• Sandell, E.-P., et al.: J. Cardiovasc. Pharmacol., 26, S57 (1995)

References