- Benzyl and sulfonyl derivatives of n-(2,6-dimethylphenyl)-2(piperazin-1-yl)acetamide (t2288): biological screening and fingerprint applications
-
A series of five N-(2,6-dimethylphenyl)-2-(piperazin-1-yl)acetamide (T2288) sulfonamides 6a-e and its five alkylated piperazine derivatives 8a-e have been synthesized, characterized and screened for antibacterial, antifungal and anthelmintic activity. Some of the compounds showed significant biological activities. Molecular docking to crystal structures of target proteins revealed that, active compounds show similar binding poses as that of standards, indicating good correlation of the binding energy with observed in vitro data for the active compounds. Finally, the study of latent fingerprint analysis showed that the compound 6c exhibits good stickiness and finger rhythm without dense dust. The resulting compound can be used to detect fingerprints on all types of flat surfaces and hence easily accepted for detecting hidden fingerprints. This research can offer an excellent setting that can lead to the discovery of potential antibacterial, antifungal, anthelmintic and fingerprint agents.
- Khan, Ghouse,Sreenivasa, Swamy,Govindaiah, Shivaraja,Chandramohan, Vivek
-
p. 157 - 166
(2019/06/05)
-
- 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.
- -
-
Paragraph 0038; 0041; 0044; 0046; 0048; 0050; 0052
(2019/03/28)
-
- NOVEL PROCESS FOR THE PREPARATION OF RANOLAZINE
-
The present invention relates to novel processes for the preparation of Ranolazine (I) and its acid addition salts and the novel process for the preparation of compound of formula (7).
- -
-
Page/Page column 17-18
(2016/09/26)
-
- 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.
- Sawant, Ganesh,Ghosh, Saptarshi,Banesh, Sooram,Bhaumik, Jayeeta,Chand Banerjee, Uttam
-
p. 49150 - 49157
(2016/06/09)
-
- COMPOSITIONS AND METHODS FOR THE TREATMENT ANGINA AND CARDIOVASCULAR CONDITIONS
-
The invention relates to the compounds of formula I or its pharmaceutical acceptable salts, as well as polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula I, and methods for the treatment of angina and cardiovascular conditions may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment of chronic aneurysm, angina, atherosclerosis, cerebrovascular accident (stroke), cerebrovascular disease, congestive heart failure, coronary artery disease, myocardial infarction (heart attack), peripheral vascular disease, aortic dissection, aortic stenosis, arrhythmia (irregular heartbeat), atrial fibrillation, cardiomyopathy, chest pain, claudication, congenital heart disease.
- -
-
-
- 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.
- -
-
Paragraph 0029; 0030
(2013/04/13)
-
- "All water chemistry" for a concise total synthesis of the novel class anti-anginal drug (RS), (R), and (S)-ranolazine
-
A novel strategy of 'all water chemistry' is reported for a concise total synthesis of the novel class anti-anginal drug ranolazine in its racemic (RS) and enantiopure [(R) and (S)] forms. The reactions at the crucial stages of the synthesis are promoted by water and led to the development of new water-assisted chemistries for (i) catalyst/base-free N-acylation of amine with acyl anhydride, (ii) base-free N-acylation of amine with acyl chloride, (iii) catalyst/base-free one-pot tandem N-alkylation and N-Boc deprotection, and (iv) base-free selective mono-alkylation of diamine (e.g., piperazine). The distinct advantages in performing the reactions in water have been demonstrated by performing the respective reactions in organic solvents that led to inferior results and the beneficial effect of water is attributed to the synergistic electrophile and nucleophile dual activation role of water. The new 'all water' strategy offers two green processes for the total synthesis of ranolazine in two and three steps with 77 and 69% overall yields, respectively, and which are devoid of the formation of the impurities that are generally associated with the preparation of ranolazine following the reported processes.
- Kommi, Damodara N.,Kumar, Dinesh,Chakraborti, Asit K.
-
p. 756 - 767
(2013/03/29)
-
- An efficient synthesis of symmetric and unsymmetric bis-(β- aminoamides) via Ugi multicomponent reaction
-
A library of symmetrical and unsymmetrical bis-(β-aminoamides) has been prepared starting from symmetrical secondary diamines by using a double Ugi four-component reaction. A sacrifical Mumm rearrangement, thanks to the use of 2-hydroxymethyl benzoic acid, is necessary to suppress the competing split-Ugi reaction, increasing the yield and simplifying the purification step. The scope, the reaction conditions, and the role of water in trapping the nitrilium intermediate are also discussed.
- La Spisa, Fabio,Feo, Alberto,Mossetti, Riccardo,Tron, Gian Cesare
-
supporting information
p. 6044 - 6047
(2013/02/23)
-
- Improved process for ranolazine: An antianginal agent
-
An improved process has been developed for the active pharmaceutical ingredient, ranolazine with 99.9% purity and 47% overall yield (including three chemical reactions and one recrystallization). Formation and control of all the possible impurities is described. All the solvents used in the process were recovered and reused. The unreacted piperazine is recovered as piperazine monophosphate monohydrate salt.
- Aalla, Sampath,Gilla, Goverdhan,Anumula, Raghupathi Reddy,Kurella, Srinivas,Padi, Pratap Reddy,Vummenthala, Prabhakar Reddy
-
p. 748 - 754
(2012/08/27)
-
- An efficient synthesis of 1-(2-Methoxyphenoxy)-2,3-epoxypropane: Key intermediate of β-adrenoblockers
-
An efficient process for the preparation of 1-(2-methoxyphenoxy)-2,3- epoxypropane, a key intermediate for the synthesis of ranolazine is described.
- Madivada, Lokeswara Rao,Anumala, Raghupathi Reddy,Gilla, Goverdhan,Kagga, Mukkanti,Bandichhor, Rakeshwar
-
p. 1660 - 1664
(2013/02/25)
-
- PREPARATION OF RANOLAZINE, ITS SALTS AND INTERMEDIATES THEREOF
-
The present patent application relates to an improved process for the preparation of Ranolazine, pharmaceutically acceptable salts and intermediates thereof. Specifically it relates to processes for preparation of 1-(2-methoxy phenoxy)-2,3-epoxy propane in substantially aqueous solvent medium and 2-chloro-N-(2,6-dimethylphenyl) acetamide without using any additional base, which are intermediates, useful in the preparation of Ranolazine and pharmaceutically acceptable salts thereof.
- -
-
Page/Page column 16
(2010/04/06)
-
- PREPARATION OF RANOLAZINE
-
Preparation of ranolazine and intermediates thereof, for use in pharmaceutical compositions comprising ranolazine.
- -
-
Page/Page column 51
(2010/04/06)
-
- A PROCESS FOR THE PREPARATION OF RANOLAZINE
-
The present invention relates to an improved and novel process for preparation of ranolazine.
- -
-
Page/Page column 9
(2010/09/17)
-
- Synthesis of ranolazine metabolites and their anti-myocardial ischemia activities
-
The anti-anginal drug Ranolazine, a partial fatty acid oxidation (pFOX) inhibitor, is thought to modulate the metabolism during myocardial ischemia by activating pyruvate dehydrogenase activity to promote glucose oxidation. Ranolazine and its five principal metabolites: CVT-2512, CVT-2513, CVT-2514, CVT-2738 and CVT-4786, were synthesized. The effect of Ranolazine and its metabolites on the ECG (electrocardiogram) of mice with myocardial ischemia induced by isoprenaline and their effect on alleviating the symptom of myocardial ischemia were tested and compared. The results showed that CVT-2738 and CVT-2513 could be protective against mice myocardial ischemia induced by isoprenaline. Within all the metabolites tested in this study, CVT-2738 exhibited the best potency, however, it was still less potent than Ranolazine.
- Yao, Zhangyu,Gong, Shubo,Guan, Teng,Li, Yunman,Wu, Xiaoming,Sun, Hongbin
-
experimental part
p. 1218 - 1222
(2010/06/16)
-
- DEUTERATED PIPERAZINE DERIVATIVES AS ANTI-ANGINAL COMPOUNDS
-
This invention relates to novel compounds of formula A that partially inhibit fatty acid oxidation and pharmaceutically acceptable salts thereof. More specifically, this invention relates to novel compounds that are derivatives of ranolazine. This invention also provides compositions comprising one or more compound of this invention and a carrier and the use of the disclosed compounds and compositions in methods of treating diseases and conditions that are beneficially treated by partial fatty acid oxidation inhibitors, such as ranolazine. (Formula A), wherein at least one of Y or R comprises a deuterium atom.
- -
-
Page/Page column 27
(2008/12/08)
-
- IMPROVED PROCESS FOR THE PREPARATION OF RANOLAZINE
-
The present invention provides an improved process for the preparation of ranolazine of formula I and pharmaceutically acceptable salts thereof, by reacting 2,6-dimethylaniline derivative with chloroacetyl chloride in the presence of base in water and resulting amide intermediate is reacted with piperazine and the resulting piperazinc derivative is further condensed with an appropriate oxirane derivative ( prepared by the reaction of 2-methoxyphenol with epichlorohydrin in the presence of base using phase transfer catalyst) in an inert solvent, and highly pure ranolazine is isolated and converted to its acid salts using excess of mineral acid.
- -
-
Page/Page column 12-15
(2008/12/05)
-
- SUBSTITUTED ACETANILIDES AND BENZAMIDES FOR THE TREATMENT OF ASTHMA AND PULMONARY INFLAMMATION
-
Substituted acetanilide or benzamide compositions or formulations for delivery by aerosolization are described. The formulation contains an efficacious amount of acetanilide or benzamide compound able to inhibit inflammation in asthmatic lungs. Compounds of the invention are formulated in 5 ml solution of a quarter normal saline having pH between 5.0 and 7.0. The method for treatment of respiratory tract inflammation by a formulation delivered as an aerosol having mass medium average diameter predominantly between 1 to 5 μ, produced by nebulization or dry powder inhaler.
- -
-
Page/Page column 48
(2008/06/13)
-
- Synthesis of T2288: From Bench Synthesis to Pilot Production
-
A practical process to make N-(2,6-dimethylphenyl)-2-piperazin-1-yl- acetamide 1 is described, starting from piperazine 2 and N-chloroacetyl-2,6- xylidine 3. The unwanted N,N′-bis-alkylated product 4 can be removed by simple filtration of the reaction mixture, while the excess of piperazine remains in the aqueous phase after extracting the filtrate with toluene at 70°C. The product precipitates from the organic phase with 68% active yield.
- Guillaume, Michel,Cuypers, Jef,Vervest, Ivan,De Smaele, Dirk,Leurs, Stef
-
p. 939 - 941
(2013/09/05)
-
- Substituted piperazine compounds
-
Novel compounds of the general formula: and pharmaceutically acceptable acid addition salts thereof, wherein the compounds are useful in therapy to protect skeletal muscles against damage resulting from trauma or to protect skeletal muscles subsequent to muscle or systemic diseases such as intermittent claudication, to treat shock conditions, to preserve donor tissue and organs used in transplants, in the treatment of cardiovascular diseases including atrial and ventricular arrhythmias, Prinzmetal's (variant) angina, stable angina, and exercise induced angina, congestive heart disease, and myocardial infarction.
- -
-
-
- Aralkyl substituted piperazine compounds
-
Novel compounds of the general formula: and pharmaceutically acceptable acid addition salts thereof, wherein the compounds are useful in therapy to protect skeletal muscles against damage resulting from trauma or to protect skeletal muscles subsequent to muscle or systemic diseases such as intermittent claudication, to treat shock conditions, to preserve donor tissue and organs used in transplants, in the treatment of cardiovascular diseases including atrial and ventricular arrhythmias, Prinzmetal's (variant) angina, stable angina, and exercise induced angina, congestive heart disease, and myocardial infarction.
- -
-
-
- Piperazino-anilido compounds
-
Novel 1,4-disubstituted piperazine compounds and pharmaceutical compositions incorporating such compounds in conjunction with orally, parenterally or rectally administrable pharmaceutically acceptable carriers are disclosed. These compounds have coronary vasodilating properties. Also disclosed are processes for preparing these compounds, and novel intermediate compounds used in such processes.
- -
-
-