142387-99-3

Basic information

• Product Name: Ranolazine
• Synonyms: Ranolazine intermediate
• CAS NO: 142387-99-3
• Molecular Formula: C24H33N3O4
• Molecular Weight: 427.542
• Mol File: 142387-99-3.mol
• Article Data: 20

Chemical Properties

• Boiling Point: 624.1°C at 760 mmHg
• Flash Point: 331.2°C
• Appearance: /
• Density: 1.174g/cm³
• Vapor Pressure: 1.94E-16mmHg at 25°C
• Refractive Index: 1.585
• Storage Temp.: RT
• Solubility: Soluble in DMSO (up to 25 mg/ml) or in Ethanol (up to 20 mg/ml).
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20° for up to 1 month.
• CAS DataBase Reference: Ranolazine(CAS DataBase Reference)
• NIST Chemistry Reference: Ranolazine(142387-99-3)
• EPA Substance Registry System: Ranolazine(142387-99-3)

Safety Data

• Hazardous Substances Data: 142387-99-3(Hazardous Substances Data)

Usage

Description

Ranolazine, with the chemical formula (142387-99-3), is an FDA-approved drug specifically designed for the treatment of chronic angina. It functions by inhibiting the late inward sodium current in heart muscle cells, which subsequently leads to a decrease in intracellular calcium levels. This medication is effective in blocking Nav 1.4, 1.5, 1.7, and 1.8 with respective IC50 values of 2.42, 6.22, 1.72(10.33), and 21.53 μM.

Uses

Used in Pharmaceutical Industry:
Ranolazine is used as a therapeutic agent for the treatment of chronic angina. It helps alleviate the symptoms of this condition by improving the efficiency of the heart's energy use and reducing the oxygen demand of the heart muscle.
Additionally, Ranolazine is used in combination with other medications such as amlodipine, beta-blockers, or nitrates to enhance the overall treatment efficacy for patients suffering from chronic angina. This combination approach aims to provide better management of the condition and improve the patient's quality of life.

References

1) Belardinelli?et al., (2006),?Inhibition of the late sodium current as a potential cardioprotective principle: effects of the late sodium current inhibitor ranolazine; Heart,?92?iv6 2) Wang?et al. (2008),?State- and Use-Dependent Block of Muscle Nav1.4 and Neuronal Nav1.7 Voltage-Gated Na+-Channel Isoforms by Ranolazine; Mol. Pharmacol.?73?940 3) Rajamani?et al., (2008),?Block of tetrodotoxin-sensitive, Na(V)1.7 and tetrodotoxin-resistant, Na(V)1.8, Na+ channels by ranolazine; Channels(Austin)?2?449

InChI:InChI=1/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)

Upstream product

• 95635-55-5 Ranolazine 
• 1427177-23-8 (RS)-2-(4-(3-chloro-2-hydroxyphenyl)piperazin-1-yl)-N-(2,6-dimethylphenyl)acetamide 
• 5294-61-1 N-(2,6-dimethylphenyl)-2-(piperazin-1-yl)acetamide 
• 87-62-7 2,6-dimethylaniline 
• 1131-01-7 2-chloro-N-(2,6-dimethylphenyl)acetamide 
• 108-05-4 vinyl acetate 
• 110-85-0 piperazine 
• 2210-74-4 2-(2-methoxy-phenoxymethyl)-oxirane 
• 25772-81-0 1-chloro-3-(2-methoxyphenoxy)-2-propyl alcohol 
• 90-05-1 2-methoxy-phenol 
• 162712-35-8 CVT-2513 

Relevant articles and documents

NMR study on (±)-1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-[(2,6- dimethylphenyl)aminocarbonylmethyl]piperazine dihydrochloride salt

(±)-1-[3-(2-Methoxyphenoxy)-2-hydroxypropyl]-4-[(2,6-dimethylphenyl) aminocarbonylmethyl]piperazine dihydrochloride salt was studied spectroscopically. Complete NMR assignments for dihydrochloride salt were made using DEPT, H-H COSY, as well as HMQC and HMBC heteronuclear correlation techniques.

A preparation method of Ranolazine

The present invention relates to the technical field of ranolazine, in particular to a ranolazine preparation method, the method comprises the following steps: piperazine through the hydroformylation reaction to obtain the 1 - formyl piperazine, then with 2 - chloro - N - (2, 6 - dimethyl-phenyl) acetamide for carrying out the alkylation reaction to obtain N - (2, 6 - dimethyl-phenyl) - 2 - (4 - formyl piperazine) acetamide, then through hydrolytic reaction to obtain N - (2, 6 - dimethyl-phenyl) - 2 - (1 - piperazinyl) acetamide, finally with 2 - (2 - methyl-phenoxymethyl) oxirane ring opening reaction to obtain the ranolazine. The invention preparation of the ranolazine purity is good, high yield.

In silico approach towards lipase mediated chemoenzymatic synthesis of (S)-ranolazine, as an anti-anginal drug

An in silico modelling based biocatalytic approach for the synthesis of drugs and drug intermediates in enantiopure forms is a rationalized methodology over the organo-chemical routes. In this study, enzyme-ligand based docking was carried out using (RS)-ranolazine, as the model drug for the screening of a suitable biocatalyst for the kinetic resolution of the racemic drug. The differential interaction of the two enantiomers with the lipase was analyzed on the basis of docking score and H-bond interaction with the amino acid residues, which helped to define the trans-esterification mechanism. Ranolazine [N-(2,6-dimethylphenyl)-2-[4-(2-hydroxy)-3-(2-methoxyphenoxy)propylpiperazin-1-yl]acetamide], an anti-anginal drug, significantly reduces the frequency of anginal attack and has also been used for the treatment of ventricular arrhythmias, and bradycardia. Various lipases were examined via computational as well as wet lab screening and Candida antartica lipase in the form of CLEA was the most efficient one for the (S)-selective kinetic resolution of (RS)-ranolazine, with highest conversion and enantiomeric excess. This is the first report of the chemo-enzymatic synthesis of (S)-ranolazine where the whole drug molecule was used for lipase catalysis. The present study showed that the combination of in silico studies and a classical wet lab approach could change the paradigm of biocatalysis.

Process for the Preparation of Ranolazine

A process for the preparation of ranolazine comprises the step of condensing N-(2,6-dimethylphenyl)-1-piperazinyl acetamide with a compound of formula (I) to obtain ranolazine, in which X is chlorine or bromine Ranolazine is prepared by condensing ring-opening halide which replaces epoxide in this process.