- Cu(OTf)2 catalyzed three component strategy for the synthesis of thienopyridine containing spirooxindoles and their cytotoxic evaluation
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Synthesis of novel spirooxindoles via a three component reaction of thienopyridines, isatins and malononitriles under copper catalysis was accomplished. This one-pot, room temperature protocol allowed the synthesis of diversely substituted spirooxindoles in good to excellent yields. Cytotoxicity towards COLO320 cells revealed that compound 5v possessing a 2,6-difluorobenzyl group (IC50 of 49.1 μM) was found to be highly potent among the screened compounds. In addition, molecular docking of compound 5v into caspase-3 receptors exhibited the largest binding energy (-10.5 kcal mol-1) compared to other compounds. The formation of a DNA ladder for compound 5v also supports the experimental results.
- Parthasarathy,Praveen,Kumar, P. Senthil,Balachandran,Perumal
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- Synthesis of Biologically Active Piperidine Metabolites of Clopidogrel: Determination of Structure and Analyte Development
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Clopidogrel is a prodrug anticoagulant with active metabolites that irreversibly inhibit the platelet surface GPCR P2Y12 and thus inhibit platelet activation. However, gaining an understanding of patient response has been limited due to imprecise understanding of metabolite activity and stereochemistry, and a lack of acceptable analytes for quantifying in vivo metabolite formation. Methods for the production of all bioactive metabolites of clopidogrel, their stereochemical assignment, and the development of stable analytes via three conceptually orthogonal routes are disclosed. (Chemical Equation Presented).
- Shaw, Scott A.,Balasubramanian, Balu,Bonacorsi, Samuel,Cortes, Janet Caceres,Cao, Kevin,Chen, Bang-Chi,Dai, Jun,Decicco, Carl,Goswami, Animesh,Guo, Zhiwei,Hanson, Ronald,Humphreys, W. Griffith,Lam, Patrick Y. S.,Li, Wenying,Mathur, Arvind,Maxwell, Brad D.,Michaudel, Quentin,Peng, Li,Pudzianowski, Andrew,Qiu, Feng,Su, Shun,Sun, Dawn,Tymiak, Adrienne A.,Vokits, Benjamin P.,Wang, Bei,Wexler, Ruth,Wu, Dauh-Rurng,Zhang, Yingru,Zhao, Rulin,Baran, Phil S.
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p. 7019 - 7032
(2015/07/27)
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- PROCESS FOR PREPARING A PHARMACEUTICAL COMPOUND
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The object of the present invention is a one-pot process for preparing the 2-acetoxy-5-(2-fluoro-α-cyclopropyl-carbonyl-benzyl)-4,5,6,7-tetrahydro-4H-tieno[3,2-c]-pyridine (prasugrel) of the formula (I) by reacting the 5,6,7,7a-tetrahydro-4H-tieno[3,2-c]-pyridine-2-on of the formula (II) with 2-bromo-1-cyclopropyl-2-(2-fluorophenyl)-etanone of the formula (III) or with 2-chloro-1-cyclopropyl-2-(2-fluorphenyl)-etanone of the formula (IIIa) and acetylating of the formed compound of the formula (IV), wherein the reaction is carried out in the presence of an organic base with an acetylation agent without isolating the compound of the formula (IV). The coupling and acetylation are carried out in the presence of the same organic base such as triethylamine, N,N-diisopropyl-ethylamine or pyridine. At the end of the process the prasugrel of the formula (I) is purified by recrystallization from an organic solvent or a mixture of solvents.
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Paragraph 0047-0056
(2013/03/26)
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- METHOD FOR PREPARING PHARMACEUTICALLY ACTIVE INGREDIENT AND INTERMEDIATES THEREOF
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The present invention is related to a safe and industrially applicable method for the preparation of 2-acetoxy-5-(2-fluoro-α-cyclopropyl- carbonyl-benzyl)-4,5,6,7-tetrahydro-4H-thieno[3,2-c]pyridine in a quality suitable for use as pharmaceutically active ingredient wherein the concentration of the impurities of the Formula.(XXIV) or (XXIVa) is reduced.
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- Processes For Preparing Prasugrel And Pharmaceutically Acceptable Salts Thereof
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Disclosed are improved processes for preparing prasugrel compound of formula-(1), its intermediates and pharmaceutically acceptable salts.
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- AN IMPROVED PROCESS FOR THE PREPARATION OF PRASUGREL HYDROCHLORIDE AND ITS INTERMEDIATES
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The present invention provides an improved process for the preparation of prasugrel and its pharmaceutical acceptable salt. Prasugrel chemically known as 2-acetoxy-5-(a- cyclopropylcarbonyl-2-fluorobenzyl)-4,5,6,7-tetrahydrothieno[3,2-c]-pyridine or 5-[2- cyclopropyl-l-(2-fluorophenyl)-2-oxoethyl]-4,5,6,7-tetrahydrothieno[3,2,-c]pyridine- 2yl acetate and having the structural formula (I) and its pharmaceutically acceptable salts. The present invention also provides an improved process for the preparation of cyclopropyl 2-fluorobenzyl ketone, 2-Fluoro-a-cyclopropyl carbonylbenzyl bromide, 5,6,7,7a Tetrahydro-4H- theino-[3,2-c]- pyridone-2 p-toluenesulfonate and its hydrochloride salt.
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- NOVEL AND IMPROVED PROCESSES FOR THE PREPARATION OF PRASUGREL, ITS INTERMEDIATES AND PHARMACEUTICALLY ACCEPTABLE SALTS
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The present invention relates to novel and improved processes for the preparation of prasugrel compound of formula-(1), its intermediates and pharmaceutically acceptable salts.
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- IMPROVED PROCESS FOR PREPARING A PHARMACEUTICAL COMPOUND
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The object of the present invention is a one-pot process for preparing the 2-acetoxy-5-(2-fluoro-α-cyclopropyl-carbonyl-benzyl)-4,5,6,7-tetrahydro-4H-tieno[3,2-c]-pyridine (prasugrel) of the formula (I) by reacting the 5,6,7,7a-tetrahydro-4H-tieno[3,2-c]-pyridine-2-on of the formula (II) with 2-bromo-1-cyclopropyl-2-(2-fluorophenyl)-etanone of the formula (III) or with 2-chloro-l-cyclopropyl-2-(2-fluorphenyl)-etanone of the formula (IIIa) and acetylating of the formed compound of the formula (IV), wherein the reaction is carried out in the presence of an organic base with an acetylation agent without isolating the compound of the formula (IV). The coupling and acetylation are carried out in the presence of the same organic base such as triethylamine, N,N-diisopropyl-ethylamine or pyridine. At the end of the process the prasugrel of the formula (I) is purified by recrystallization from an organic solvent or a mixture of solvents.
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- PROCESS FOR PREPARING PHARMACEUTICAL COMPOUNDS AND INTERMEDIATE COMPOUNDS
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The object of the present invention is a process for preparing the 2-acetoxy-5-(2-fluor-α- cyclopropyl-carbonyl-benzyl)-4,5,6,7-tetrahydro-4H-tieno[3,2-c]pyridine (prasugrel) of the formula (I). The process starts form crystalline 5-trityl-4,5,6,7-tetrahydro-tieno[3,2- c]pyridine of the formula (VI). Further objects of the present invention are two novel crystalline forms of 5-trityl-4,5,6,7- tetrahydro-tieno[3,2-c]pyridine of the formula (VI) and the use thereof for preparing the compound of the formula (V) and process preparing thereof.
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- IMPROVED PROCESS FOR THE PREPARATION OF PRASUGREL AND ITS PHARMACEUTICALLY ACCEPTABLE SALTS
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The present invention relates to an improved process for the preparation of prasugrel compound of formula- 1 and its pharmaceutically acceptable salts thereof.
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Page/Page column 15; 19
(2009/06/27)
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- PROCESSES FOR THE PREPARATION OF PRASUGREL, AND ITS SALTS AND POLYMORPHS
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Processes for the preparation of prasugrel and its pharmaceutically acceptable salts thereof. Also disclosed are polymorphic forms of prasugrel hydrochloride and processes for their preparation.
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Page/Page column 39-40
(2009/06/27)
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- Derivatives of alpha-(2-oxo 2,4,5,6,7,7a-hexahydro thieno[3,2-c]5-pyridyl) phenyl acetic acid, and their use as platelet and thrombotic aggregation inhibitors
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The present invention relates to novel derivatives of alpha-(2-oxo 2,4,5,6,7,7a-hexahydro thieno [3,2-c] 5-pyridyl) phenyl acetic acid corresponding to the following general formula: STR1 their addition salts with pharmaceutically-acceptable inorganic or organic acids as well as isomers and their mixtures. The invention also relates to their process of preparation and to medicaments containing these compounds which are of therapeutic use as inhibitors of platelet- and thrombotic-aggregation.
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