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

• ChemBase编号: 798
• 分子式: C14H12N6O
• 平均质量: 280.28468
• 单一同位素质量: 280.10725903
• SMILES: O=C1NN=C([C@@H](C1)C)c1ccc(NN=C(C#N)C#N)cc1
• Canonical SMILES: N#CC(=NNc1ccc(cc1)C1=NNC(=O)C[C@H]1C)C#N
• 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

名称和登记号

名称

• IUPAC标准名: 1-cyano-N-{4-[(4R)-4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl]phenyl}methanecarbohydrazonoyl cyanide
• IUPAC传统名: levosimendan
• 商标名: Simendan; Simdax
• 别名: (-)-OR-1259; (R)-Simendan; 2-[2-[4-[(4R)-1,4,5,6-Tetrahydro-4-methyl-6-oxo-3-pyridazinyl]phenyl]hydrazinylidene]-propanedinitrile; OR 1259; R)-((4-(1,4,5,6-Tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl)hydrazono) propanedintrile; Levosimendan; [[4-[(4R)-1,4,5,6-Terahydro-4-methyl-6-oxo-3-pyridazinyl]phenyl]hydrazono]propanedinitrile; OR-1259; Simdax; Levosimedan; Levosimendan

登记号

• CAS号: 141505-33-1
• MDL号: MFCD00867135
• PubChem SID: 46507149; 160964261
• PubChem CID: 3033825

理论计算性质

JChem

• Acid pKa: 10.534338
• 质子受体: 6
• 质子供体: 2
• LogD (pH = 5.5): 2.0628319
• LogD (pH = 7.4): 2.159906
• Log P: 2.1616182
• 摩尔折射率: 77.6308 cm^3
• 极化性: 27.841526 Å^3
• 极化表面积: 113.43 Å^2
• 可自由旋转的化学键: 3
• 里宾斯基五规则: true

ALOGPS 2.1

• Log P: 2.69
• LOG S: -3.5
• 溶解度: 8.81e-02 g/l

分子性质

理化性质

• 溶解度: DMSO; DMSO: ≥20 mg/mL; Methanol
• 外观: yellow powder; Yellow Solid
• 熔点: 216-219°C (dec.)
• 比旋光度: [α]/D -500 to -650°, c = 0.5 in THF

安全信息

• 保存条件: -20°C Freezer
• RTECS编号: TY1570210
• 欧盟危险性物质标志: 有害性(Harmful) (Xn)
• 德国WGK号: 3
• 危险公开号: 20/21/22
• 安全公开号: 36/37
• GHS危险品标识: GHS07
• GHS警示词: Warning
• GHS危险声明: H302-H312-H332
• GHS警示性声明: P280
• 保存温度: room temp

产品相关信息

• 纯度: ≥98% (HPLC)
• Empirical Formula (Hill Notation): C14H12N6O

详细说明

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 Ca^2+-sensitizing inotropic agent. Ca^2+ 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 Ca^2+ 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.

Toronto Research Chemicals - L378000

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

参考文献

• 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
• Sandell, E.-P., et al.: J. Cardiovasc. Pharmacol., 26, S57 (1995)
• Pagel, P.S., et al.: Cardiovasc. Drug Rev., 14, 286 (1995)