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

• ChemBase ID: 120
• Molecular Formular: C12H9N3O
• Molecular Mass: 211.21936
• Monoisotopic Mass: 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

NAMES AND DATABASE IDS

Names

• IUPAC name: 6-methyl-2-oxo-5-(pyridin-4-yl)-1,2-dihydropyridine-3-carbonitrile
• IUPAC Traditional name: milrinone
• Brand Name: Corotrop; Corotrope; Milrila; Primacor
• Synonyms: 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

Database IDs

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

CALCULATED PROPERTIES

JChem

• Acid pKa: 7.536811
• H Acceptors: 3
• H Donor: 1
• LogD (pH = 5.5): 0.2525552
• LogD (pH = 7.4): 0.12443696
• Log P: 0.3290194
• Molar Refractivity: 61.1381 cm^3
• Polarizability: 22.2292 Å^3
• Polar Surface Area: 65.78 Å^2
• Rotatable Bonds: 1
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 1.04
• LOG S: -3.0
• Solubility (Water): 2.09e-01 g/l

PROPERTIES

Physical Property

• Solubility: DMSO; DMSO: >10 mg/mL; H2O: insoluble; Slightly soluble
• Apperance: off-white powder; Off-White Solid
• Melting Point: 305-308°C (dec.)
• Density: 0.87 g/ml
• Hydrophobicity(logP): 0.4

Safety Information

• Storage Condition: -20°C; Refrigerator
• RTECS: DW1762000
• European Hazard Symbols: Toxic (T)
• UN Number: 2811
• German water hazard class: 3
• Hazard Class: 6.1
• Packing Group: 3; III
• Australian Hazchem: 2X
• Risk Statements: 23/24/25; R:25
• Safety Statements: 36/37/39-45; S:28-29-36/37/39-45
• EU Classification: T2
• EU Hazard Identification Number: 6.1B
• Emergency Response Guidebook(ERG) Number: 154
• GHS Pictograms: GHS06
• GHS Signal Word: Danger
• GHS Hazard statements: H301-H311-H331
• GHS Precautionary statements: P261-P280-P301 + P310-P311
• Personal Protective Equipment: Eyeshields, Faceshields, Gloves, type P2 (EN 143) respirator cartridges
• RID/ADR: UN 2811 6.1/PG 3
• Storage Temperature: 2-8°C

Pharmacology Properties

• Gene Information: human ... PDE3A(5139), PDE3B(5140), PDE4B(5142), PDE5A(8654), PTPRA(5786)rat ... Pde3a(50678)

Product Information

• Purity: ≥97% (TLC); 97%
• Salt Data: Free Base

DETAILS

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.

REFERENCES

• 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)