- The invention relates to a synthetic method of. Intermediate and synthetic method
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The invention belongs to the technical field of drug synthesis, and discloses a synthesis method, an intermediate and a synthesis method of amideamine, and solves the problems of complex operation, high production cost, no suitability for industrialization and environmental friendliness in the prior art. To the formula VIII, a compound of formula VII is produced by a one-pot method, a compound of formula VII is subjected to a one-pot method to form an intermediate formula IV compound of, and a compound of formula IV and a compound of formula II are cyclized to obtain the compound of formula I. The method is simple to operate, few in procedures, low in production cost, and high in product yield and purity.
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Paragraph 0079-0084
(2021/11/27)
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- 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 0135-0136
(2020/12/29)
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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 0023; 0028
(2019/04/04)
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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 33; 34
(2019/06/17)
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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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- 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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- Preparation method of enzalutamide intermediate
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The invention discloses a preparation method of an enzalutamide intermediate and belongs to the field of pharmaceutical and chemical industry. According to the preparation method of the enzalutamide intermediate, the reaction of every process is high up to higher than 80%, certain reaches up to 93%. Meanwhile, the preparation method of the enzalutamide intermediate is simple in aftertreatment process, easy to operate and applicable to industrializing, mild in reaction conditions and free from severe reaction conditions of high temperature, high pressure and ultralow temperature.
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Paragraph 0026; 0035; 0036; 0038
(2018/08/28)
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- SUBSTITUTED TRICYCLIC 1,4-BENZODIAZEPINONE DERIVATIVES AS ALLOSTERIC MODULATORS OF GROUP II METABOTROPIC GLUTAMATE RECEPTORS
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The present invention provides novel tricyclic 1,4-benzodiazepinone derivatives of the general formula (I) and pharmaceutical compositions containing them. Moreover, the compounds of formula (I) and the pharmaceutical compositions containing them are provided for use in the treatment and/or prophylaxis of conditions associated with altered glutamatergic signalling and/or functions, and/or conditions which can be affected by alteration of glutamate level or signalling in mammals. The tricyclic 1,4-benzodiazepinone derivatives of formula (I) can act as modulators of nervous system receptors sensitive to glutamate, in particular as modulators of metabotropic glutamate receptors (mGluRs), which makes them particularly suitable for the treatment and/or prophylaxis of acute and chronic neurological and/or psychiatric disorders. The present invention further provides tricyclic 1,4-benzodiazepinone derivatives of formula (I) that are modulators of metabotropic glutamate receptors (mGluRs), particularly positive allosteric modulators of mGluRs, and more specifically positive allosteric modulators of mGluR3. (I)
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Page/Page column 228-229
(2017/05/28)
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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 14; 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; 0022-0024
(2017/03/14)
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- HIGHLY SELECTIVE C-MET INHIBITORS AS ANTICANCER AGENTS
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Disclosed are novel nitrogen-containing, heterocyclic, c-Met inhibitor compounds, processes for their preparation and formulations thereof. The compounds are useful as therapeutical agents for the inhibition, regulation, and control of c-Met kinase signal pathway, and useful for treating in a subject a cell proliferative disorder or disorders mediated by c-Met.
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Page/Page column 9
(2014/03/25)
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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 43
(2011/09/30)
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- Imidazole pyrimidine amides as potent, orally bioavailable cyclin-dependent kinase inhibitors
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The development of a novel series of imidazole pyrimidine amides as cyclin-dependent kinase (CDK) inhibitors is described. The series was found to have much improved CDK2 inhibition and potent in vitro anti-proliferative effects against cancer cell lines. Control of overall lipophilicity was important to achieve good in vitro potency along with acceptable physiochemical properties and margins against inhibition of both CYP isoforms and the hERG potassium ion channel. A compound with an attractive overall balance of properties was profiled in vivo and possessed suitable physiochemical and pharmacokinetic profiles for oral dosing.
- Jones, Clifford D.,Andrews, David M.,Barker, Andrew J.,Blades, Kevin,Byth, Kate F.,Finlay, M. Raymond V.,Geh, Catherine,Green, Clive P.,Johannsen, Marie,Walker, Mike,Weir, Hazel M.
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body text
p. 6486 - 6489
(2009/10/01)
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- BIPHENYLOXYACETIC ACID DERIVATIVES FOR THE TREATMENT OF RESPIRATORY DISEASE
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The invention relates to substituted phenoxyacetic acids of formula (I), where the variables are as defined in claim 1, as useful pharmaceutical compounds for treating respiratory disorders, pharmaceutical compositions containing them, and processes for their preparation.
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Page/Page column 74
(2008/06/13)
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- 4- (4- (IMIDAZOL-4-YL) PYRIMIDIN-2-YLAMINO) BENZAMIDES AS CDK INHIBITORS
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Compounds of the formula: (I): wherein variable groups are as defined within and a pharmaceutically acceptable salts and in vivo hydrolysable esters are described. Also described are processes for their preparation and their use as medicaments, particularly medicaments for producing a cell cycle inhibitory (anti-cell-proliferation) effect in a warm-blooded animal, such as man.
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Page/Page column 63
(2008/06/13)
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- Inhibitors of hepatitis C virus RNA-dependent RNA polymerase, and compositions and treatments using the same
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The invention relates to compounds of the formula 1 and to pharmaceutically acceptable salts, solvates, prodrugs and metabolites thereof, wherein W, Z, R1 and R2, are as defined herein. The invention also relates to methods of treating Hepatitis C virus in mammals by administering the compounds of formula 1, and to pharmaceutical compositions for treating such disorders, which contain the compounds of formula 1. The invention also relates to methods of preparing the compounds of formula 1.
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Page/Page column 21
(2008/06/13)
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- INHIBITORS OF HEPATITIS C VIRUS RNA-DEPENDENT RNA POLYMERASE, AND COMPOSITIONS AND TREATMENTS USING THE SAME
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The invention relates to compounds of the formula (I) and to pharmaceutically acceptable salts, solvates, prodrugs and metabolites thereof, wherein W, Z, R1and R2, are as defined herein. The invention also relates to methods of treating Hepatitis C virus in mammals by administering the compounds of formula (I), and to pharmaceutical compositions for treating such disorders, which contain the compounds of formula (I). The invention also relates to methods of preparing the compounds of formula (I).
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