6-methyl-2-oxo-5-(pyridin-4-yl)-1,2-dihydropyridine-3-carbonitrile

• ChemBase编号: 120
• 分子式: C12H9N3O
• 平均质量: 211.21936
• 单一同位素质量: 211.07456192
• SMILES: O=c1[nH]c(c(c2ccncc2)cc1C#N)C
• Canonical SMILES: N#Cc1cc(c2ccncc2)c([nH]c1=O)C
• InChI: InChI=1S/C12H9N3O/c1-8-11(9-2-4-14-5-3-9)6-10(7-13)12(16)15-8/h2-6H,1H3,(H,15,16)
• InChIKey: PZRHRDRVRGEVNW-UHFFFAOYSA-N

名称和登记号

名称

• IUPAC标准名: 6-methyl-2-oxo-5-(pyridin-4-yl)-1,2-dihydropyridine-3-carbonitrile
• IUPAC传统名: milrinone
• 商标名: Corotrop; Corotrope; Milrila; Primacor
• 别名: 1,6-Dihydro-2-methyl-6-oxo-(3,4′-bipyridine)-5-carbonitrile; Milrinone; Primacor; Milrinone Lactate; Milrinone; 1,6-Dihydro-2-methyl-6-oxo-3,4-bipyridine-5-carbonitrile; 1,6-Dihydro-2-methyl-6-oxo-[3,4'-bipyridine]-5-carbonitrile; Corotrope; Milrila; Win 47203

登记号

• CAS号: 78415-72-2
• EC号: 278-903-6
• MDL号: MFCD00133539
• PubChem SID: 46507838; 160963583; 24278060
• PubChem CID: 4197

理论计算性质

JChem

• Acid pKa: 7.536811
• 质子受体: 3
• 质子供体: 1
• LogD (pH = 5.5): 0.2525552
• LogD (pH = 7.4): 0.12443696
• Log P: 0.3290194
• 摩尔折射率: 61.1381 cm^3
• 极化性: 22.2292 Å^3
• 极化表面积: 65.78 Å^2
• 可自由旋转的化学键: 1
• 里宾斯基五规则: true

ALOGPS 2.1

• Log P: 1.04
• LOG S: -3.0
• 溶解度: 2.09e-01 g/l

分子性质

理化性质

• 溶解度: DMSO; DMSO: >10 mg/mL; H2O: insoluble; Slightly soluble
• 外观: off-white powder; Off-White Solid
• 熔点: 305-308°C (dec.)
• 密度: 0.87 g/ml
• 疏水性(logP): 0.4

安全信息

• 保存条件: -20°C; Refrigerator
• RTECS编号: DW1762000
• 欧盟危险性物质标志: 有毒(Toxic) (T)
• 联合国危险货物编号: 2811
• 德国WGK号: 3
• 联合国危险货物等级: 6.1
• 联合国危险货物包装类别(PG): 3; III
• 澳大利亚Hazchem: 2X
• 危险公开号: 23/24/25; R:25
• 安全公开号: 36/37/39-45; S:28-29-36/37/39-45
• 欧盟危险货物分类: T2
• 欧盟危险识别号(EUHIN): 6.1B
• 美国ERG指导号: 154
• GHS危险品标识: GHS06
• GHS警示词: Danger
• GHS危险声明: H301-H311-H331
• GHS警示性声明: P261-P280-P301 + P310-P311
• 个人保护装置: Eyeshields, Faceshields, Gloves, type P2 (EN 143) respirator cartridges
• RID/ADR: UN 2811 6.1/PG 3
• 保存温度: 2-8°C

药理学性质

• 相关基因信息: human ... PDE3A(5139), PDE3B(5140), PDE4B(5142), PDE5A(8654), PTPRA(5786)rat ... Pde3a(50678)

产品相关信息

• 纯度: ≥97% (TLC); 97%
• 成盐信息: Free Base

详细说明

MP Biomedicals - 02158962

Purity: 97%
Specifically inhibits cGMP-inhibited phosphodiesterase. Strong cardiotonic positive inotropic vasodilator.

DrugBank - DB00235

• Drug Groups: approved
• Description: A positive inotropic cardiotonic agent with vasodilator properties. It inhibits cAMP phosphodiesterase activity in myocardium and vascular smooth muscle. Milrinone is a derivative of amrinone and has 20-30 times the ionotropic potency of amrinone. [PubChem]
• Indication: Indicated for the treatment of congestive heart failure.
• Pharmacology: Milrinone, a synthetic dimethylxanthine derivative structurally related to theophylline and caffeine, is used in the treatment of peripheral vascular diseases and in the management of cerebrovascular insufficiency, sickle cell disease, and diabetic neuropathy.
• Toxicity: LD₅₀ = 0.3 mg/L in rats
• Affected Organisms: Humans and other mammals
• Biotransformation: There are five metabolites but the O-glucuronide represents the major pathway of biotransformation.
• Absorption: Milrinone is rapidly and almost completely absorbed after oral administration. Bioavailability is 92% (in healthy volunteers).
• Half Life: 2.3 hours
• Protein Binding: 70 to 80%
• Elimination: The primary route of excretion of milrinone in man is via the urine.
• Distribution: * 0.38 liters/kg [intravenous injections of 12.5 mcg/kg to 125 mcg/kg to congestive heart failure patients]; * 0.45 liters/kg [intravenous infusions of 0.20 mcg/kg/min to 0.70 mcg/kg/min to congestive heart failure patients]
• Clearance: * 0.13 L/kg/hr [congestive heart failure patients, following IV injections of 12.5 mcg/kg to 125 mcg/kg]; * 0.14 L/kg/hr [congestive heart failure patients, following infusions of 0.2 mcg/kg/min to 0.7 mcg/kg/min]
• External Links: Wikipedia; RxList; Drugs.com

Selleck Chemicals - S2484

Research Area: Cardiovascular Disease
Biological Activity:
Milrinone(Primacor) is a a potent and selective phosphodiesterase 3 inhibitor with an IC50 of 0.42 µM for the inhibition of FIII PDE. [1] It potentiates the effect of cyclic adenosine monophosphate (cAMP). It also enhances relaxation of the left ventricle by increasing Ca2+-ATPase activity on the cardiac sarcoplasmic reticulum. This increases calcium ion uptake.It has positive inotropic, vasodilating and minimal chronotropic effects. It is used in the management of heart failure only when conventional treatment with vasodilators and diuretics has proven insufficient. This is due to the potentially fatal adverse effects of milrinone, including ventricular arrhythmias. [2]

Sigma Aldrich - M4659

Biochem/physiol Actions
Phosphodiesterase type III inhibitor; cAMP-specific, cGMP-inhibitable; potent cardiotonic, positive inotropic vasodilator.

Toronto Research Chemicals - M344680

Selective phosphodiesterase inhibitor with vasodilating and positive inotropic activity. Cardiotonic.

参考文献

• Harrison, S.A., et al., Mol. Pharmacol. , 29 : 506 (1986).
• Ahn, S., et al., Biochem. Pharmacol. , 35 : 1113 (1986).
• Alousi, A.A., et al., J. Cardiovas. Pharmacol. , 5 : 792 (1983).
• Ito M et al. Biochem Pharmacol. 1988 May 15;37(10)
• Alousi, A.A., et al.: J. Cardiovasc Pharmacol., 5, 792 (1983)
• Maskin, C.S., et al.: Circulation, 67, 1065 (1983)
• Sinoway, L.S., et al.: J. Am. Coll. Cardiol., 2, 327 (1983)
• Baim, D.S., et al.: N. Engl. J. Med., 309, 748 (1983)