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Ranolazine

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CAS:95635-55-5
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Ranolazine Basic information
Description References
Product Name:Ranolazine
Synonyms: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;Ranolazine (100 mg)
CAS:95635-55-5
MF:C24H33N3O4
MW:427.54
EINECS:620-450-7
Product Categories:Aromatics;Heterocycles;Intermediates & Fine Chemicals;Inhibitors;RANEXA;Pharmaceuticals;Antianginal;API;APIs
Mol File:95635-55-5.mol
Ranolazine Structure
Ranolazine Chemical Properties
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
solubility DMSO (Slightly), Methanol (Slightly)
pka14.06±0.20(Predicted)
form Solid
color White
Major Applicationpharmaceutical small molecule
InChI1S/C24H33N3O4/c1-18-7-6-8-19(2)24(18)25-23(29)16-27-13-11-26(12-14-27)15-20(28)17-31-22-10-5-4-9-21(22)30-3/h4-10,20,28H,11-17H2,1-3H3,(H,25,29)
InChIKeyXKLMZUWKNUAPSZ-UHFFFAOYSA-N
SMILESN2(CCN(CC2)CC(=O)Nc3c(cccc3C)C)CC(O)COc1c(cccc1)OC
CAS DataBase Reference95635-55-5(CAS DataBase Reference)
Safety Information
WGK Germany WGK 3
HS Code 2933595960
Storage Class11 - Combustible Solids
Hazardous Substances Data95635-55-5(Hazardous Substances Data)
MSDS Information
Ranolazine Usage And Synthesis
DescriptionRanolazine ([(+)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
DescriptionRanolazine 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 PropertiesWhite Solid
OriginatorRoche Bioscience (US)
Usesantianginal, antiischemic
DefinitionChEBI: 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 nameRanexa (Sensus).
General DescriptionRanolazine, 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 UseAdd on therapy for angina
SynthesisTwo 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.

Synthesis_95635-55-5

Drug interactionsPotentially 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.
MetabolismExtensively 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.
References[1] Patent: US2008/312247, 2008, A1. Location in patent: Page/Page column 31-32
[2] Patent: WO2006/8753, 2006, A1. Location in patent: Page/Page column 7; 8
[3] Organic Process Research and Development, 2012, vol. 16, # 10, p. 1660 - 1664
Tag:Ranolazine(95635-55-5) Related Product Information
Propyl gallate 2-Cyanoacetamide Acetamide CHLOROPHOSPHONAZO III Propyl butyrate Thioacetamide N,N-Dimethylacetamide Ranolazine Dihydrocloride,Ranolazine2Hcl,RANOLAZINE DIHYDROCHLORIDE,RANOLAZINE HCL,Ranolazine DiHCI ,Ranolazine and salt,RANOLAZINE DI HCL Lidocaine hydrochloride N-(2,6-Diphenylmethyl)-1-piperazine acetylamine 2',6'-DIMETHYLACETANILIDE Guaiacol glycidyl ether Ranolazine-d3 Desmethyl Ranolazine -D-Glucuronide O-Desaryl Ranolazine Desmethyl Ranolazine Ranolazine-d5 Ranolazine

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