94 results about "Enzalutamide" patented technology

The invention discloses an enzalutamide soft capsule and a preparation method thereof. The enzalutamide soft capsule comprises capsule content and a capsule shell, wherein the capsule content comprises enzalutamide and pharmaceutical adjuvants; the capsule shell is formed by gelatin, glycerin, sorbitol, titanium dioxide, purified water and the like. The soft capsule can be prepared with the method comprising following steps: Labrasol, butylated hydroxyanisole, butylated hydroxytoluene and enzalutamide are mixed to obtain the capsule content material of the soft capsule; the gelatin, the glycerin, the sorbitol, titanium dioxide and the purified water are mixed to obtain the capsule shell material of the soft capsule; the capsule content material and the capsule shell material of the soft capsule are pelleted on a soft capsule making machine to obtain the enzalutamide soft capsule. The enzalutamide soft capsule and the preparation method have the following advantages: the soft capsule is convenient to administrate and carry, the drug stability is good, effective components are dissolved quickly, and the bioavailability is high.

The invention provides a preparation method of enzalutamide. The method comprises the following steps: adding a compound with formula F to a solvent; reacting with a methylamine source; and after the reaction, collecting the compound with formula G from the reaction products, so as to obtain the enzalutamide. The invention overcomes the major problems of the prior art, gets rid of the time-consuming and labor-consuming operation such as column chromatography, gets rid of the highly toxic reagent such methyl iodide, and has the advantages of mild reaction conditions, simple and easy post-treatment, increased overall yield, reaction time reduction, production cost reduction, and applicability to industrial scale-up. The reaction general formula is as below.

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.

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.

The invention discloses a novel method for compounding enzalutamide, belongs to the technical field of pharmacy synthetic technology, and particularly relates to novel technology for compounding enzalutamide. Most known methods for compounding enzalutamide relate to use of highly toxic and mephitical thiophosgene and highly toxic oxobutyronitrile, and have relatively great difficulty for industrialization. According to the invention, non-toxic and harmless thiourea and an isobutyric acid derivative are used for a reaction to obtain a key parent nucleus of 5,5-dimethyl-2-thioketone imidazole-4-ketone, and therefore, thiophosgene and oxobutyronitrile are effectively avoided. The method has a mild reaction condition, is relatively high in yield, and therefore has a great industrial prospect.

The present invention relates to an insulin-like growth factor (IGF) receptor antagonist for use in the treatment of prostate neoplasia, including benign prostatic hyperplasia (BPH), prostate cancer, and particularly CRPC, wherein the antagonist is used in combination with an androgen receptor antagonist. An embodiment of the invention is where the androgen receptor antagonist is enzalutamide.

The invention provides a preparation process of a prostatic cancer medicine Enzalutamide. The preparation process includes: with N-methyl-4-bromo-2-fluoro-benzamide being a raw material, performing acatalytic nucleophilic substitution reaction with 2-amino isobutyric acid under alkaline condition to generate 2-(3-fluoro-4-(methylcarbamoyl)phenylamino)-2-methylpropionic acid; performing esterification to generate 2-methoxyethyl-2-((3-fluoro-4-(methylcarbamoyl)phenyl)amino)-2-methylpropionate; performing a ring closing reaction on the product with 2-trifluoromethyl-4-isothiocyanobenzonitrile togenerate the finish product 4-(3-(4-cyano-3-trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-sulfoimidazole-1-yl)-2-fluoro-N-methylbenzamide, namely, Enzalutamide. The method overcomes the major defectsin the prior art and avoids use of high-toxic reagent such as iodomethane, is gentle in reaction conditions and is convenient and simple in after treatment, is improved in total yield and reduced in reaction time, is reduced in preparation cost, is green and environment-friendly, and is suitable for industrial large-scale production.

The invention relates to the field of chemical synthesis and in particular relates to synthesis of a medicine enzalutamide for treating male late castration-resistant prostate cancer. The method is characterized by comprising the following steps: by taking 2-fluoro-4-nitrotoluene as a raw material, sequentially performing oxidation, acylation and reduction, thereby obtaining N-methyl-2-fluoro-4-aminobenzamide; carrying out a nucleophilic reaction between N-methyl-2-fluoro-4-aminobenzamide and ethyl 2-bromoisobutyrate, condensing the generated 2-(3-fluoro-4-methylamino formyl phenyl) amino aniline-2-methylethyl propionate and 4-isothiocyanic-2-trifluoromethylbenzonitrile in the presence of a condensing agent, thereby obtaining the enzalutamide. The method disclosed by the invention is easy to operate, stable, reliable and mild in conditions, application of a toxic reagent is reduced, the total reaction yield is more than 20 percent, the purity of the synthesized product is high and is larger than 99.0 percent.

The invention discloses an application of auranofin (Aura) in preparation of a medicine for treating castration-resistant prostate cancer (CRPC), and belongs to the technical field of biological medicines. The invention provides a new strategy used for preparing the CRPC treatment medicine from the Aura and based on combined use of Enza and Aura for the first time, and multi-angle and multi-levelverification research is carried out. The Aura can be used for treating the castration-resistant prostate cancer, significantly improves the castration-resistant prostate cancer inhibition effect of the Enza, realizes new use of the old drug, can greatly shorten the time from drug discovery to clinical transformation, and has important clinical treatment significance.

The invention provides a preparation method of an enzalutamide intermediate F. The method comprises the steps of: (1) reacting a compound with a formula D and a compound with a Formula E in a solvent; (2) after the reaction, cooling to room temperature and adding a protic solvent; and (3) adding a polar solvent, and then collecting the compound with the formula F from the reaction products. The preparation process has the advantages of easily available raw materials, easy reaction operation, simple post-treatment and no usage of hazardous reagent in the preparation method, and is applicable to industrial production. The reaction general formula is as below.

The invention discloses a novel method for compounding a medicament of Enzalutamide for resisting the prostate cancer, belongs to the technical field of pharmacy synthetic technique, and particularly relates to novel technique for compounding Enzalutamide. Most of known methods for compounding Enzalutamide relate to use of highly toxic and mephitical thiophosgene and highly toxic oxobutyronitrile and have great difficulty in industrialization. According to the invention, a non-toxic and harmless Lawesson's agent is adopted, and a key parent nucleus of a carbonyl group is subjected to a sulfenylation reaction, so that thiophosgene and oxobutyronitrile are effectively avoided. The reaction condition of the method is mild, and the yield is relatively high, therefore, the novel method has a great industrialization prospect.

The invention provides lncRNA related to enzalutamide treatment sensitivity and application of the lncRNA to prostate cancer treatment by enzalutamide, and relates to the field of biological gene technologies. The lncRNA related to the enzalutamide treatment sensitivity is lnc-OPHN1-5, and the lnc-OPHN1-5 can increase the sensitivity of prostate cancer (PCa) to the enzalutamide (Enz) by reducing the translation of ARmRNA and the synthesis of AR protein. The lncRNA related to the enzalutamide treatment sensitivity overcomes the disadvantages of the prior art, and provides a new medical idea andstrategy for the treatment of castrated resistant prostate cancer (CRPC) and through the application of the lnc-OPHN1-5 in the prostate cancer treatment by the enzalutamide to improve the survival cycle of patients.

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.

The present application relates to crystalline and amorphous forms of Enzalutamide. The present application further relates to amorphous solid dispersions of Enzalutamide with pharmaceutically acceptable carriers. The present application also relates to a process for the preparation of Form R1 of Enzalutamide.

The purpose of the present invention is to provide a new process for producing an enzalutamide crystal form which is reduced in the contents of 2-propanol and B-form crystals, the process including obtaining wet crystals of enzalutamide in a crystallization step during the production of the enzalutamide crystal form and subsequently subjecting the enzalutamide to solvation. The present invention relates to a process for producing an enzalutamide crystal form, characterized by including a crystallization step in which wet crystals of enzalutamide are obtained and a step for drying the wet crystals and by including, after the crystallization step, a cleaning step in which a solvent mixture of a good solvent and a poor solvent is used.

The invention relates to the field of medical technique research and discloses a prostatic cancer stem cell marker, application of an antibody OV6 in the preparation of a prostatic cancer stem cell marking material and a marking method. The marking method comprises the following steps: marking a prostate cancer cell line or a prostate tissue cell by virtue of a mouse-source OV6 antibody; incubating the prostate cancer cell line or the prostate tissue cell together with rat anti-mouse IgG and magnetic beads; putting the prostate cancer cell line or the prostate tissue cell on an MACS MS column,and carrying out filtration separation, so as to obtain an OV6 positive prostatic cancer cell; and finally detecting the marking efficiency of the OV6 positive prostatic cancer cell by virtue of a flow cytometry. Furthermore, enzalutamide is utilized for realizing drug stimulation so as to enhance the marking effect before the marking of the mouse-source OV6 antibody. According to the marking method, the prostatic cancer stem cell can be remarkably marked, and the OV6 positive cell has high expression dryness-related gene and high granulation rate and tumor formation rate. The marking methodhas relatively high specificity and sensitivity and important clinical values.

The invention provides an indazole hydrazide compound as shown in a formula (I), wherein R is selected from substituted alkyl, substituted alkenyl or substituted phenyl; substituent groups in the substituted alkyl group and the substituted alkenyl group comprise phenyl and/or substituted phenyl; and R' is selected from H or alkyl. Compared with the prior art, the indole hydrazide compound provided by the invention can be used as an integrin avbeta3 receptor antagonist, has obvious anti-prostatic cancer activity, and has a significant inhibition effect on enzalutamide drug-resistant cell lines.

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.

The invention provides a preparation method of enzalutamide. The method comprises the following steps: condensing an initial raw material 2-((3-fluoro-4-(methylcarbamoyl)phenyl)amino)-2-methylpropioric acid and enol to obtain an intermediate I, and reacting the intermediate I with The method has the advantages of simple operation, suitableness for industrial production, high yield and high purity.

The invention provides a method for synthesizing enzalutamide. Specifically, the preparation method comprises the following steps: (1) in a first solvent, in the presence of an inorganic base, a catalyst and a ligand, enabling a compound 8 to react with hydrochloride of a compound shown as a formula I, thereby obtaining a compound 9; wherein the first solvent is composed of an organic solvent 1 and water; and (2) reacting the compound 9 and the compound 7 in a second solvent in the presence of an organic base to obtain enzalutamide. The preparation method has the advantages of short synthesisroute, high yield, mild reaction conditions, simple operation and post-treatment, high product purity, and suitableness for industrial production.

The invention belongs to the technical field of pharmaceutical synthesis methods, and provides a preparation method of enzalutamide. The method includes: (1) a step of preparing a compound B, namely astep of reacting 2-((3-fluoro-4-(methylcarbamoyl)phenyl)amino)-2-methylpropanoicacid as an initial raw material in an organic solvent with the presence of an inorganic alkali or an organic alkali ata proper temperature to obtain the compound B; (2) a step of reacting the compound B prepared by the step (1) with 4-isothiocyanato-2-(trifluoromethyl)benzonitrile to obtain the target product enzalutamide. The method avoids use of high-toxicity reagents such as iodomethane, shortens the preparation time for the compound B, avoids complex operation in aftertreatment of the enzalutamide, greatly simplifies an aftertreatment process, facilitates resource saving and is more suitable for industrial scale-up production.

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).

The invention discloses a purification method of enzalutamide. According to the method, a coarse enzalutamide product is added to a recrystallization vessel and dissolved through an alcohol or amide organic solvent; a hydrocarbon solvent is dropwise added while agitating, wherein the dropwise adding speed is controlled and a crystal precipitate of materials in the system can be gradually separated out, and after the dropwise adding is done, the solid can be separated out; the solid can be filtered to obtain the fine enzalutamide product. By virtue of the method, the problems such as instantaneous caking and impurities occurring in recrystallization of enzalutamide can be solved; the method is suitable for industrial production; the enzalutamide product obtained by recrystallization has the purity more than 99.5%, and the recrystallization yield is more than 75%; an enzalutamide preparation is processed according to the requirements of standard on raw medicines in Chinese Pharmacopoeia, so that a patient can use safely.