Nicorandil

Nicorandil Basic information
Product Name:Nicorandil
Synonyms:n-[2-(nitroxy)ethyl]-3-pyridinecarboxamide;N-[2-(NITROOXY)ETHYL]-3-PYRIDINECARBOXAMIDE;2-[(Pyridin-3-ylcarbonyl)amino]ethyl nitrate, N-[2-(Nitroxy)ethyl]pyridine-3-carboxamide;3-Pyridinecarboxamide, N-[2-(nitrooxy)ethyl]-;SG-75;Dancor;Nitric acid 2-nicotinoylaminoethyl ester;2-(pyridin-3-ylcarbonylamino)ethyl nitrate
CAS:65141-46-0
MF:C8H9N3O4
MW:211.17
EINECS:265-514-1
Product Categories:Pharmaceutical;Ikorel;Intermediates & Fine Chemicals;Potassium channel;reagent;Cardiovascular APIs;Pharmaceuticals;Aromatics;Heterocycles;65141-46-0
Mol File:65141-46-0.mol
Nicorandil Structure
Nicorandil Chemical Properties
Melting point 92°C
Boiling point 350.85°C (rough estimate)
density 1.4271 (rough estimate)
refractive index 1.7400 (estimate)
RTECS US4667600
storage temp. 2-8°C
solubility DMSO: >10mg/mL
form powder
pka12.70±0.46(Predicted)
color white to off-white
Merck 14,6521
CAS DataBase Reference65141-46-0
Safety Information
Hazard Codes Xn
Risk Statements 22-41
Safety Statements 26-39
WGK Germany 3
HS Code 29333990
ToxicityLD50 in rats (mg/kg): 1200-1300 orally; 800-1000 i.v. (Nagano)
MSDS Information
Nicorandil Usage And Synthesis
Chemical PropertiesNicorandil is N-(2-hydroxyethyl)-nicotinamide nitrate (ester). It is a white crystalline powder or white needles with a faint, characteristic odour. It is freely soluble in methanol, ethanol, acetone or glacial acetic acid, slightly soluble in chloroform or water, almost insoluble in ether or benzene. Melting point 88.5-93.5 ℃. Acute toxicity LD50 rat (mg/kg): 1200-1300 orally, 800-1000 intravenously.
OriginatorChugai (Japan)
UsesNicorandil is a vasodilator used for the prophylaxis and treatment of angina. This medication widens blood vessels thus increasing the blood and oxygen flow to the heart. It is not currently available in the US.
Nicorandil is a nitric oxide donor and ATP-sensitive potassium channel opener. A study showed that Nicorandil is able to protect against stress-induced cell death in dystrophin-deficient cardiomyocytes and also preserve cardiac function in the mdx mouse heart subjected to ischemia and reperfusion injury.
DefinitionChEBI: Nicorandil is a pyrimidinecarboxamide that is nicotinamide in which one of the hydrogens attached to the carboxamide nitrogen is replaced by a 2-(nitrooxy)ethyl group. It has both nitrate-like and ATP-sensitive potassium channel activator properties, and is used for the prevention and treatment of angina pectoris. It has a role as a vasodilator agent and a potassium channel opener. It is a pyridinecarboxamide and a nitrate ester. It derives from a nicotinamide.
PreparationNicorandil is obtained by treating nicotinic acid chloride hydrochloride with nitro-oxy-ethyl-amine nitrate in an organic solvent.
synthesis of Nicorandil
Nicorandil was synthesized from 2-aminoethanol by a four step process. In order to protect the amino group during nitration, 2-aminoethanol was first treated with phthalic anhydride. The amide formed was then nitrated using a nitrating mixture and was subsequently deprotected by reacting with hydrazine hydrate. The 2- nitroxyethylamine obtained was condensed with nicotinoyl chloride in pyridine. Treatment with aqueous sodium bicarbonate solution gave nicorandil as free base.
synthesis of Nicorandil
Brand nameSIGMART; PERISALOL
Biochem/physiol ActionsNicorandil is a hybrid ATP-sensitive K+ (KATP) channel opener and nicotinamide nitrate NO donor. Nicorandil selectively activates SUR2B- versus SUR2A-containing KATP channels. It enhances endothelial NO synthase expression and protects against ischemic ventricular arrhythmias. By activating potassium channels, and donating nitric oxide to activate the enzyme guanylate cyclase, Nicorandil causes activation of GMP leading to both arterial and venous vasodilatation. Nicorandil is selective for vascular potassium channels, but has no significant action on cardiac contractility and conduction.
Clinical UseNicorandil is used for the prevention and treatment of chronic stable angina. It is usually used when angina becomes difficult to control by other drugs and is given as an additional treatment.
Drug interactionsPotentially hazardous interactions with other drugs
Avanafil, sildenafil, tadalafil and vardenafil: enhanced hypotensive effect - avoid.
Riociguat: possible enhanced hypotensive effect - avoid.

MetabolismMetabolism of nicorandil is mainly by denitration of the molecule into the nicotinamide pathway. About 20% of a dose is excreted in the urine mainly as metabolites
Mode of actionThe coronary vasodilating activity of nicorandil is considered to be the consequence of the increasing cyclic GMP production by stimulating guanylyl cyclase in the coronary vascular smooth muscle, similar to other nitrates/nitrites (in vitro). In addition, other mechanisms such as hyperpolarization of the cell membrane were investigated concerning its coronary blood flowincreasing and coronary vasospasmolytic effects.
The vasorelaxant effect of nicorandil in isolated blood vessels is suppressed by an ATP-sensitive K channel blocker or a guanylate cyclase inhibitor. Moreover, in a canine model of acute heart failure, the cardiac haemodynamics-improving effect of the drug (e.g. effect of increasing the aortic blood flow) was suppressed by an ATP-sensitive K channel blocker. Furthermore, the drug caused an increase in the cGMP content in isolated blood vessels. These facts suggest that the vasodilating effect of the drug is related to the effect of opening the ATP-sensitive K channel, as well as to the effect of increasing production of cGMP.
Nicorandil Preparation Products And Raw materials
Raw materialsNitric acid-->Monoethanolamine-->2-N-BUTOXYETHYL METHACRYLATE-->Methyl nicotinate-->Nicotinoyl chloride hydrochloride
3-Pyridinecarboxaldehyde-D4 Nicotinamide Nicorandil Ethanol N-(2-HYDROXYETHYL)NITOTINAMIDE Nicorandil fumaric acid salt Aminoethyl nitrate Ethylparaben NICORANDIL NICOTINAMIDE-2,4,5,6-D4 Ethyl nitrate Ethyl acetate Ethyl vanillin Ethyl nitrite Ethyl acrylate NICORANDIL-D4,NICORANDIL-D4 (PYRIDYL-D4) Ethyl 4'-hydroxy-3'-methoxycinnamate NICORANDIL = N[2-(NITROOXY)ETHYL]3-PYRIDINECARBOXAMIDE

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