Chemical Properties
White Solid
Originator
Roche Bioscience (US)
Uses
antianginal, antiischemic
Uses
Ranolazine is an anti-ischemic agent which modulates myocardial metabolism. Antianginal.
Definition
ChEBI: N-(2,6-dimethylphenyl)-2-{4-[2-hydroxy-3-(2-methoxyphenoxy)propyl]piperazin-1-yl}acetamide is an aromatic amide obtained by formal condensation of the carboxy group of 2-{4-[2-hydroxy-3-(2-methoxyphenoxy)propyl]piperazin-1-yl}acetic acid with the amino group of 2,6-dimethylaniline. It is a monocarboxylic acid amide, an aromatic amide, a N-alkylpiperazine, a secondary alcohol and a monomethoxybenzene.
Brand name
Ranexa (Sensus).
General Description
Ranolazine, N-(2,6-dimethylphenyl)-2-[4-[2-hydroxy-3-(2-methoxyphenoxy)propyl]piperazin-1-yl]acetamide (Ranexa), is an antianginal medication thatwas approved by the Food and Drug Administration (FDA)in January 2006 for the treatment of chronic angina.Ranolazine is believed to elicit its effects by altering thetranscellular late sodium current. This, in turn, alters thesodium-dependent calcium channels during myocardial ischemia.Thus, ranolazine indirectly prevents the calciumoverload that is associated with cardiac ischemia.Ranolazine is metabolized by the cytochrome CYP3A enzymesin the liver.
Clinical Use
Add on therapy for angina
Synthesis
Two syntheses,
one from the inventors at Roche and other from a group in Hungary, of Ranolazine have been described in the
patent literature. The original synthesis is highlighted in the
Scheme. Reaction of 2,6-dimethylaniline 46 with chloroacetyl
chloride (47) in the presence of triethylamine for 4h at
0oC gave amide 48 in 82% yield. This chloro amide 48 was
reacted with piperazine in refluxing ethanol for 2 h to give
piperazinyl amide 50. Reaction of amide 50 with epoxide
intermediate 53, prepared by reacting 2-methoxy phenol 51
with epichlorohydrin, in refluxing isopropanol for 3 h followed
by treatment with HCl/methanol gave ranolazine dihydrochloride
(VII) in 73% yield.
Drug interactions
Potentially hazardous interactions with other drugs
Anti-arrhythmics: avoid with disopyramide.
Antibacterials: concentration possibly increased
by clarithromycin and telithromycin - avoid
concomitant use; concentration reduced by
rifampicin - avoid.
Antifungals: concentration increased by ketoconazole
and possibly itraconazole, posaconazole and
voriconazole - avoid.
Antivirals: concentration possibly increased by
atazanavir, darunavir, fosamprenavir, indinavir,
lopinavir, ritonavir, saquinavir and tipranavir - avoid.
Beta-blockers: avoid with sotalol.
Ciclosporin: concentration of both drugs possibly
increased.
Grapefruit juice: concentration of ranolazine possibly
increased - avoid.
Statins: concentration of simvastatin increased -
maximum dose of simvastatin is 20 mg.
Tacrolimus: concentration of tacrolimus increased.
Metabolism
Extensively metabolised in the gastrointestinal tract and
liver. Four main metabolites have been identified.
Approximately 75% of a dose is excreted in the urine with
the remainder in the faeces.
