Levosimendan

Levosimendan Basic information
Product Name:Levosimendan
Synonyms:LEVOSIMENDAN;-2-[[4-(1,4,5,6-Tetrahydro-4-methyl-6-oxo-3-pyridazinyl)19henyl]hydrazono]Propandinitrile;(R)-Simendan;[[4-[(4R)-1,4,5,6-Terahydro-4-methyl-6-oxo-3-pyridazinyl]phenyl]hydrazono]propanedinitrile;OR-1259;Simda;Mesoxalonitrile (-)-{p-[(R)-1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl]phenyl}hydrazone;(R)-2-[[4-(1,4,5,6-TETRAHYDRO-4-METHYL-6-OXO-3-PYRIDAZINYL)PHENYL] HYDROZONO]PRO
CAS:141505-33-1
MF:C14H12N6O
MW:280.28
EINECS:663-528-6
Product Categories:Inhibitors;FLUOTHANE;Intermediates & Fine Chemicals;Pharmaceuticals
Mol File:141505-33-1.mol
Levosimendan Structure
Levosimendan Chemical Properties
Melting point 216-219°C (dec.)
alpha D25 -566° (tetrahydrofurane/methanol)
density 1.33±0.1 g/cm3(Predicted)
storage temp. room temp
solubility DMSO: ≥20mg/mL
pka6.3(at 25℃)
form powder
color yellow
optical activity[α]/D -500 to -650°, c = 0.5 in THF
Safety Information
Hazard Codes Xn
Risk Statements 20/21/22
Safety Statements 36/37
WGK Germany 3
RTECS TY1570210
HS Code 2933.99.7500
ToxicityLD50 in male, female mice, male rats (mg/kg): 156, 152, 103 orally; 32, 50, 57 i.v. (Pagel)
MSDS Information
ProviderLanguage
Levosimendan English
Levosimendan Usage And Synthesis
DescriptionLevosimendan was introduced in Sweden as an i.v. infusion for the treatment of acute heart failure or refractory symptoms of chronic heart failure in cases where conventional treatment (e.g., diuretic or ACE inhibitor) is not sufficient. Levosimendan is the (R)- enantiomer of simendan that belongs to the same class as pimobendan (Boehringer Ingelheim).
Chemical PropertiesYellow Crystalline Powder
OriginatorOrion (Finland)
UsesLevosimendan is a positive inotropic agent that acts by sensitising troponin C to Ca2+, prolonging actin-myosin cross-bridge formation and therefore increasing contractility. This is an energy-independent process and therefore does not increase myocardial oxygen demand. Levosimendan also causes vasodilatation by opening ATP-sensitive K+ channels in vascular smooth muscle, reducing pre- and afterload and improving myocardial oxygen supply. It may have a role in the management of acute heart failure and postresuscitation myocardial dysfunction.
DefinitionChEBI: Levosimendan is a hydrazone, a pyridazinone and a nitrile. It has a role as a vasodilator agent, an EC 3.1.4.17 (3',5'-cyclic-nucleotide phosphodiesterase) inhibitor, a cardiotonic drug and an anti-arrhythmia drug.
Brand nameSimdax (Orion Pharmaceutica, Finland).
General DescriptionLevosimendan is a calcium sensitizer that can cause increased cardiac contractility by binding troponin C (EC50 = 9 nM), promotes vasodilation by activating ATP-sensitive potassium channels on vascular smooth muscle cells (EC50 = 0.28 μM), and performs a cardioprotective function by prompting the opening of mitochondrial potassium channels in cardiomyocytes. It also has been reported to inhibit phosphodiesterases 3 and 4 in left ventricular cardiac tissue with IC50 values of 2.5 nM and 25 μM, respectively.
Biochem/physiol ActionsLevosimendan has a potential to inhibit both acute human immunodeficiency virus type 1 (HIV-1) replication and the reactivation of latent HIV-1 proviruses. Therefore, it is considered to be a promising anti-HIV-1 agent.
Clinical UseLevosimendan is the bioactive enantiomer of racemate of Simendan. It acts as a positive inotropic agent with vasodilating activity. Levosimendan functions as a cardiotonic agent, promoting cardiac function and increasing blood vessel dilation. Levosimendan has been used for screening its anti-human immunodeficiency virus type 1 (HIV-1) property. It has also been used for screening its cytotoxic effects in TP53 mutant and wild-type lung adenocarcinoma cell lines.
Mode of actionLevosimendan is an innovative myofilament calcium sensitizer that increases myocardial contractility by selectively binding to the N-terminus of troponin C and by stabilizing the Ca2+-bound conformation of this contractile protein. It also activates ventricular and arterial adenostne triphosphate-regulated potassium channels which causes vasodilatation in vascular smooth muscle and protects myocardium against infarction. Its low phosphodiesterase III inhibiting activity is probably not responsible for its positive inotropic, lusitropic and dilating effects. Unlike other cardiotonic drugs, levosimendan is able to produce positive inotropic effects without prolonging myocardial relaxation or increasing the incidence of malignant arrythmias. It was clinically shown to have a lower risk of mortality in patients with heart failure when compared to placebo and dobutamine. Since it has a larger potential, levosimendan is currently under further clinical evaluation as a chronic treatment for congestive heart failure.
Levosimendan Preparation Products And Raw materials
Raw materials1,4-Dioxane-->Sodium acetate-->Malononitrile-->Pyridazine
LEVOSIMENDAN DAZINONES INTERMEDIATES Levodopa LEVOSIMENDAN DAZINONES INTERMEDIATES Methyl 6-(4-aminophenyl)-4,5-dihydro-5-methyl-3(2h)-pyridazinone (intermediate of levosimendan) Levamisole Parathion-methyl L-carnitine Tribenuron methyl Levosimendan Kresoxim-methyl Thiophanate-methyl Pirimiphos-methyl Methyl salicylate (R)-6-(4-AMINOPHENYL)-5-METHYLPYRIDAZIN-3(2H)ONE 101328-85-2 (INTERMEDIATE OF LEVOSIMENDAN) Methyl acetate Methyl bromide METSULFURON METHYL

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