- Method for synthesizing enzalutamide (by machine translation)
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The invention provides a method for synthesizing enzalutamide. , The preparation method comprises the following steps: (1) in first solvent, reacting the compound 8 with the hydrochloride of the compound of formula I in the presence of an inorganic base, a catalyst and a ligand to obtain the compound 9. The first solvent is composed of an organic solvent 1 and water. And (2) In 2nd-solvent, the compound 9 and the compound 7 are reacted in the presence of an organic base, thereby obtaining enzalutamide. The preparation method has the advantages of short synthetic route, high yield, mild reaction conditions, simple operation and post-treatment, high product purity and suitability for industrial production. (by machine translation)
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Paragraph 0101; 0137-0138
(2020/12/29)
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- Preparation process of medicine enzalutamide of prostate cancer (by machine translation)
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The preparation process, of the present invention overcomes the major drawbacks N - of the prior art by catalyzing the nucleophilic substitution reaction, with 2 - methyl - 4 4 (methylcarbamoyl, phenyl,methyl propionic acid 2 - (3 -) to generate)-trifluoromethyl) - 2 - phenyl,(methylcarbamoyl,phenylamino 2 -methyl propionate 2 - ((3 -) by esterification.). The method of the present invention overcomes the major drawback, of the prior art, by catalyzing the nucleophilic substitution reaction) to react with) - 2 -methoxyethyl,yl 2 -methylpropanoic acid in the presence of a nucleophilic substitution reaction with, methyl - 4 4-(methylamino) isobutyric acid in the presence. of a nucleophilic substitution. 4 - (3 - (4 - The present invention provides, a method for producing prostate cancer, drug enrolirubin) by, a catalytic reaction with isothiocyanobenzonitrile in accordance with the present, invention in the, state of the present invention in the present invention . and is suitable for large-scale industrial production of the product) - 5,5 - cyano - 3 3- (methylcarbamoyl) N-methylpropanoic acid is shown in Table) - 2 . (by machine translation)
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Paragraph 0015
(2020/03/17)
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- Method for synthesizing enzalutamide intermediate
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The invention discloses a method for synthesizing an enzalutamide intermediate. The method is characterized by comprising the following steps: adding 4-bromo-2-fluorobenzoic acid and sulfoxide chloride into an organic solvent, evacuating and introducing nitrogen, and carrying out a reaction at a temperature of 80-100 DEG C; evaporating the solvent to dryness so as to obtain 4-bromo-2-fluorobenzoylchloride after the reaction ends, adding the organic solvent into the 4-bromo-2-fluorobenzoyl chloride, slowly adding an aqueous solution of methylamine to regulate the pH value of the reaction solution to be 8-9, and continuing to carry out the reaction; extracting with the organic solvent after the reaction ends, collecting the organic phase, and evaporating the solvent to dryness, thereby obtaining the 4-bromo-2-fluoro-N-methylbenzamide. According to the method disclosed by the invention, the 4-bromo-2-fluorobenzoic acid and 2-aminoisobutyric acid are taken as the raw materials, the product is prepared by a substitution reaction under the actions of cuprous halide catalysis, ligand assistance and in the presence of an acid-binding agent, and the yield is 75%. However, by virtue of theoptimized conditions, cheap acetylacetone is screened as a ligand, and the cost is greatly reduced.
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Paragraph 0024-0025; 0028
(2019/04/04)
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- A new series of bicalutamide, enzalutamide and enobosarm derivatives carrying pentafluorosulfanyl (SF5) and pentafluoroethyl (C2F5) substituents: Improved antiproliferative agents against prostate cancer
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SAR studies on bicalutamide, enobosarm and enzalutamide analogues, functionalised with polyfluorinated groups, is presented. Among the novel bicalutamide and enobosarm derivatives synthesised, several displayed significantly improved in vitro anticancer activity, with IC50 values in the low micromolar range against four different prostate cancer cell lines (LNCaP, VCaP, DU-145 and 22Rv1), showing up to 48-fold increase in comparison with the parent structures. In particular, SF5 enobosarm analogues were found to be most potent compounds, full AR antagonists and with favourable ADME properties. The most promising compound (48a) was evaluated for its in vivo efficacy in PC xenograft mouse model (22Rv1) with results comparable to the standard-of-care docetaxel.
- Pertusati, Fabrizio,Ferla, Salvatore,Bassetto, Marcella,Brancale, Andrea,Khandil,Westwell, Andrew D.,McGuigan, Christopher
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- PROCESS FOR PREPARATION OF ENZALUTAMIDE USING NOVEL INTERMEDIATE
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Process for preparation of Enzalutamide using novel intermediate Provided herein is a process for the preparation of a novel [4-cyano-3- (trifluoromethyl)phenyl]carbamodithioic acid and its use in preparation of Enzalutamide being cost effective with higher yield, higher HPLC purity with reduced impurities.
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Page/Page column 34; 35
(2019/06/17)
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- Method for preparing enzalutamide synthesis intermediate compound represented by formula (III)
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The invention discloses a method for preparing an enzalutamide synthesis intermediate compound represented by a formula (III), wherein the compound represented by the formula III is an important intermediate for preparing an anti-prostate cancer drug enzalutamide. The method comprises: carrying out a reaction by using a compound represented by a formula (I) and a compound represented by a formula(II) as raw materials to produce the compound represented by the formula (III).
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Paragraph 0011
(2019/10/01)
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- Synthesis of androgen receptor antagonists containing a pentafluorosulfanyl (SF5) moiety
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A novel scaffold of pentafluorosulfanyl (SF5)-containing enzalutamide analogues was discovered for potent androgen receptor (AR) antagonists through rational drug design. Several compounds showed good biological profiles in AR binding. Of the derivatives studied, compound 8a had potent AR antagonist activity (IC50 = 7.1 ± 1.0 μM) and high efficacy (104.5 ± 12.8%). It exhibited an inhibitory effect comparable to that of enzalutamide (inhibition = 66.0 and 77.9%, respectively) in a prostate cancer cell line. The results point to the potential of using this scaffold to develop new AR antagonists.
- Jin, Jiyu,Zhou, Yan,Yang, Dehua,Zhang, Qiumeng,Wang, Ming-Wei,Lu, Wei
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- PROCESS FOR PREPARATION OF ANDROGEN RECEPTOR ANTAGONIST
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The present invention provides an isopropanol solvate of enzalutamide. The present invention also provides a process for the preparation of androgen receptor antagonist. In particular, the present invention provides a process for the preparation of enzalutamide or its pharmaceutically acceptable salts, hydrates, solvates, polymorphs or intermediates thereof.
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Paragraph 0117
(2017/06/27)
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- Enzalutamide intermediate preparation method
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The present invention discloses an enzalutamide intermediate preparation method, wherein 2-bromo-4-fluoro-N-methylbenzamide and 2-amino-isobutyric acid are subjected to a substitution reaction under catalysis of cuprous halide, assisted catalysis of a nitrogen-containing ligand and the effect of an acid-binding agent, and the nitrogen-containing ligand is proline, o-phenanthroline, 8-hydroxy quinoline, metformin or 1,8-diazabicycloundec-7-ene. According to the present invention, the method has characteristics of safety, environmental protection, simple operation, low cost, high product yield, and great production use value.
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Paragraph 0023; 0024; 0025; 0026; 0027
(2016/10/07)
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- AN IMPROVED PROCESS FOR THE PREPARATION OF ENZALUTAMIDE
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The present application relates to an improved process for preparation of Enzalutamide (I). The present application also relates to an improved process for the preparation of substantially pure Enzalutamide (I) having purity of greater than 99.5%. The present application also relates to a novel process for the preparation of Enzalutamide intermediate useful in the industrially viable synthesis of Enzalutamide.
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Page/Page column 15
(2016/04/26)
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- A "one-pot synthesis" method of synthesizing graciousness mixed Lu An
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The invention provides a one-pot method for synthetizing enzalutamide and belongs to the field of medicinal chemical synthesis. The method comprises the following steps: firstly, carrying out copper-catalyzed Buchwald reaction on N-methyl-4-bromo-2-fluoro-benzamide and 2-methyl alanine, adding halogenated hydrocarbon, reacting to generate ester, finally adding a key intermediate 4-isothiocyano-2-(trifluoromethyl) cyanophenyl and carrying out bucherer-Bergs reaction to generate the enzalutamide. The method is simple in operation and high in product yield and has the advantages that the intermediate products are not needed to be separated and directly reacted, so that the process flow cycle is shortened; the final product is easy to separate and purify.
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Paragraph 0017; 0026-0028
(2017/03/14)
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- A PROCESS FOR PRODUCING ENZALUTAMIDE
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This invention provides a new process for producing enzalutamide of formula I, starting from the intermediate of formula XI, which cyclizes with the isothiocyanate of formula VIII in the presence of a base, an alcohol of the general formula R-OH as an additive, in a suitable solvent, wherein R is an alkyl with the number of carbon atoms C1C20, or a substituted alkyl with the number of carbon atoms C1C20, an aryl with the number of carbon atoms C6-C16, or a substituted aryl with the number of carbon atoms C6-C16.
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- PROCESS FOR PREPARATION OF ANDROGEN RECEPTOR ANTAGONIST
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The present invention provides an isopropanol solvate of enzalutamide. The present invention also provides a process for the preparation of androgen receptor antagonist. In particular, the present invention provides a process for the preparation of enzalutamide or its pharmaceutically acceptable salts, hydrates, solvates, polymorphs or intermediates thereof.
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Paragraph 0084; 0085
(2015/08/04)
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- PROCESSES FOR THE SYNTHESIS OF DIARYLTHIOHYDANTOIN AND DIARYLHYDANTOIN COMPOUNDS
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Processes are provided for the synthesis of diarylthiohydantoin and diarylhydantoin compounds, such as compounds of the formula: wherein X, Y1, Y2, R1, and R2 are as defined herein. Medicinal products containing the same find particular use in treating prostate cancer, including castration-resistant prostate cancer and/or hormone-sensitive prostate cancer.
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Page/Page column 44
(2011/09/30)
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