Ranolazine CAS NO.95635-55-5

Product Name:    Ranolazine
Synonyms:    (142387-99-3) ranolazine;1- 3-(2-Methoxyphenoxy)-2-hydroxypropyl -4- ...;1-Piperazineacetamide,N-(2,6-dimethylphenyl)-4-[2-hydroxy-3-(2-methoxyphenoxy)propyl]-;N-(2,6-dimethylphenyl)-2-[4-[2-hydroxy-3-(2-methoxyphenoxy)propyl]piperazin-1-yl]ethanamide;N-(2,6-diMethylphenyl)-2-{4-[(2R)-2-hydroxy-3-(2-Methoxyphenoxy)propyl]piperazin-1-yl}acetaMide;Ranolazine(Ranexa);100MG/500MG/1KG;Ranolazine N-(2,6-Dimethylphenyl)-2-[4-[2-hydroxy-3-(2-methoxyphenoxy)propyl]piperazin-1-yl]acetamide
CAS:    95635-55-5
MF:    C24H33N3O4
MW:    427.54
EINECS:    620-450-7               
Mol File:    95635-55-5.mol                            

Melting point     119-1200C
Boiling point     624.1±55.0 °C(Predicted)
density     1.174±0.06 g/cm3(Predicted)
storage temp.     Sealed in dry,Room Temperature
pka    14.06±0.20(Predicted)
CAS DataBase Reference    95635-55-5(CAS DataBase Reference)
Safety Information
HS Code     2933595960
Hazardous Substances Data    95635-55-5(Hazardous Substances Data)
MSDS Information
Ranolazine Usage And Synthesis
Description    Ranolazine ([(+)N-(2,6-dimethylphenyl)-4(2-hydroxy-3-(2-methoxyphenoxy)-propyl)-1-piperazine acetamide dihydrochloride]) is an active piperazine derivative that was patented in 1986 and is available in an oral and intravenous form. Ranolazine is evidenced with anti-ischemic/antianginal properties in patients with chronic angina without clinically significant changes in heart rate or blood pressure.  
Ranolazine is used for the treatment of angina (chronic chest pain). Researches show it also has potential use in cardiovascular conditions such as heart failure, acute and chronic myocardial ischemia, certain types of cardiac sodium channel gene mutations, and ventricular and supraventricular arrhythmias.
References    [1] Bernard R. Chaitman, Ranolazine for the Treatment of Chronic Angina and Potential Use in Other Cardiovascular Conditions, New Drugs and Technologies, 2006, vol. 113, 2462-2472
[2] Bernard R. Chaitman, Sandra L. Skettino, John O. Parker, Peter Hanley, Jaroslav Meluzin, Jerzy Kuch and Carl J. Pepine, Anti-ischemic effects and long-term survival during ranolazine monotherapy in patients with chronic severe angina, Journal of the American College of Cardiology, 2004, vol. 43, 1375-1382
Description    Ranolazine is an orally available, extended release drug for the treatment of chronic angina in patients who have failed to respond to prior angina therapy. Chronic stable angina (CSA) is a common symptom of coronary artery disease wherein plaques in the coronary vasculature restrict blood flow to the heart, which in turn leads to insufficient oxygenation of the heart, typically during physical exertion or emotional stress. A vast majority of the existing anti-anginal and anti-ischemic therapies aim to correct the imbalance between myocardial oxygen demand and supply through mechanisms that produce reductions in heart rate or blood pressure.
Chemical Properties    White Solid
Originator    Roche Bioscience (US)
Uses    antianginal, antiischemic
Uses    Ranolazine is an anti-ischemic agent which modulates myocardial metabolism. Antianginal.
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.
Chemical 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.