Levosimendan CAS 141505-33-1
Introduction：Basic information about Levosimendan CAS 141505-33-1, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
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 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 |
| form | powder |
| pka | 6.3(at 25℃) |
| color | yellow |
| Optical Rotation | [α]/D -500 to -650°, c = 0.5 in THF |
| 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 |
| SMILES | C(#N)/C(=N/NC1=CC=C(C2=NNC(=O)C[C@H]2C)C=C1)/C#N |
Safety Information
| Hazard Codes | Xn |
| Risk Statements | 20/21/22 |
| Safety Statements | 36/37 |
| WGK Germany | 3 |
| RTECS | TY1570210 |
| HS Code | 2933.99.7500 |
| Storage Class | 11 - Combustible Solids |
| Hazard Classifications | Acute Tox. 4 Dermal Acute Tox. 4 Inhalation Acute Tox. 4 Oral |
| Toxicity | LD50 in male, female mice, male rats (mg/kg): 156, 152, 103 orally; 32, 50, 57 i.v. (Pagel) |
| Description | Levosimendan 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 Properties | Yellow Crystalline Powder |
| Originator | Orion (Finland) |
| Uses | Levosimendan 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. |
| Definition | ChEBI: 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 name | Simdax (Orion Pharmaceutica,Finland). |
| General Description | Levosimendan 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 Actions | Levosimendan 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 Use | Levosimendan 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 action | Levosimendan 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. |
| References | [1] M S NIEMINEN. Levosimendan: current data, clinical use and future development.[J]. Heart, lung and vessels, 2013, 5 4: 227-245. [2] ZOLTáN PAPP. Pharmacological Mechanisms Contributing to the Clinical Efficacy of Levosimendan[J]. Cardiovascular Therapeutics, 2006, 23 1: 71-98. DOI: 10.1111/j.1527-3466.2005.tb00158.x [3] SZABOLCS SZILáGYI . The effects of levosimendan and OR-1896 on isolated hearts, myocyte-sized preparations and phosphodiesterase enzymes of the guinea pig[J]. European journal of pharmacology, 2004, 486 1: Pages 67-74. DOI: 10.1016/j.ejphar.2003.12.005 |
Levosimendan Preparation Products And Raw materials
| Raw materials | 1,4-Dioxane-->Sodium acetate-->Malononitrile-->Pyridazine |
