- Histone deacetylase inhibitors and its preparation method and use thereof
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The invention discloses a histone deacetylase inhibitor and its preparation method and use, the invention discloses a compound of the formula I as shown, or its crystalline form, or its pharmaceutically acceptable salt, or solvate thereof, or prodrug thereof, or its metabolic product. The invention of the formula I illustrated new compound, has shown good deacetylase inhibition activity, with the histone deacetylase for clinical treatment of diseases associated with abnormal activity of a new pharmaceutical may be.
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Paragraph 0127; 0129; 0130; 0131; 0132
(2019/05/15)
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- Synthesis method of 5-bromo-7-azaindole
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The invention relates to a synthesis method of 5-bromo-7-azaindole. With 7-azaindole as a raw material, conjugation of the five-membered ring of indole is damaged by low-pressure liquid-phase hydrogenation, and a key medical intermediate 5-bromo-7-azaindole is prepared through oxybromination and nonmetal oxydehydrogenation. The product purity is higher than or equal to 99%. Bromine atoms are introduced by an oxybromination technology, the utilization rate of the bromine atoms exceeds 98%, the use of bromine is avoided, and the problem that a large amount of bromine-containing waste liquid is generated in original technology is solved. According to the synthesis method provided by the invention, through nonmetal catalytic dehydrogenation, heavy metal catalysis is avoided, the problem of heavy metal residue easily occurring in the product is solved, and the safety of medicine products is ensured. The reaction efficiency can be effectively improved, the reaction time is shortened, and thetotal reaction yield is increased; moreover, industrial waste liquid and residue is reduced, industrial popularization is facilitated, and remarkably high economic benefits are created.
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- Synthesis method of 5-bromo-7-azaindole
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The invention discloses a synthesis method of 5-bromo-7-azaindole. With 7-azaindole as the raw material, hydrogenation reduction, bromination and dehydrogenation are conducted, a platinum-carbon catalyst is added for catalyzing 7-azaindole to conduct hydrogenation to prepare dihydro-7-azaindole, catalysis efficiency is improved, and reaction energy consumption and reaction time are decreased; 5-bromo-7-azaindoline is synthesized by adding sodium bromide for catalysis, a mixture of chromic oxide, zinc oxide and magnesium oxide is added for substituting manganese dioxide for catalytic dehydrogenation reaction, reaction time can be effectively shortened, and reaction yield is increased. By means of the method, reaction efficiency can be effectively improved, reaction time is shortened, the total reaction yield is increased, process waste liquid and waste slag are reduced, industrial popularization is facilitated, and extremely high economic benefits are achieved.
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- A 5-bromo-7-aza-indole synthesis process (by machine translation)
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This invention relates to a kind of 5-bromo-7-aza-indole synthesis process, the steps of: the 7-aza indole, Raney nickel, ethanol stirring and hydrogen; reacting filtering, the filter cake is washed with ethanol washing, combined filtrate, concentrated dry, be 7-aza indole [...] ; the crude product with toluene-P-sulfonic acid, methylene chloride mixed, and stirring instillment bromide ; sodium hyposulfite washing the reaction solution, the organic phase is dried with anhydrous sodium sulfate, concentrated to obtain 5-bromo-7-aza-indoline product; the product is dissolved in toluene, adding manganese dioxide, heating reflux reaction; filtering the reaction liquid, the filter cake washed with methylene chloride, combined organic phase, dried, concentrated to obtain 5-bromo-7-azaindoles crude, PE/EA mixed solution for crystallization to obtain the finished product. The invention has the advantages of low cost, simple process, the operation is simple, and the like, is suitable for large-scale factory production, this method generating the purity of the product in 99% or more, the yield of 74% or more, comprehensive utilization rate is high. (by machine translation)
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- Production process of 5-bromo-7-azaindole
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The invention relates to a production process of 5-bromo-7-azaindole. The production process includes following steps: (1), using 7-azaindole as a raw material, and enabling 7-azaindole to be in catalytic hydrogenation under action of a catalyst-palladium loaded mesoporous carbon to generate dihydro-7-azaindole; (2), enabling dihydro-7-azaindole to be in bromination reaction under action of hydrogen bromide and hydrogen peroxide to generate dihydro-5-bromo-7-azaindole, where a feeding molar ratio of dihydro-7-azaindole, hydrogen bromide and hydrogen peroxide is 1:10-30:1-2, and temperature for bromination reaction is 20-30 DEG C; (3), enabling dihydro-5-bromo-7-azaindole to be in oxidative dehydrogenation under action of manganese dioxide/glacial acetic acid to generate 5-bromo-7-azaindole. The production process has the advantages of high reaction yield and low cost.
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- HISTONE DEACETYLASE INHIBITORS
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Fused bicycle indol, indoline, azoindole, or azoindoline compounds of Formula (I) set forth herein. Also disclosed are pharmaceutically acceptable salts of these compounds and pharmaceutical compositions containing the same. Further disclosed is a method for treating cancer, e.g., glioma, prostate cancer, and colorectal cancer, with these compounds.
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Page/Page column 37
(2015/11/03)
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- 7-azaindol-3-ylacrylamides active as kinase inhibitors
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Compounds represented by Formula (I) wherein R1 and R2 are as defined in the specification, compositions thereof, and methods of use thereof.
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Page/Page column 101
(2009/07/10)
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- NOVEL ANTIMALARIA AGENT CONTAINING HETEROCYCLIC COMPOUND
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Disclosed is an antimalarial agent containing a compound represented by the formula: [wherein A1 represents a 3-pyridyl group that may have a substituent, a 6-quinolyl group that may have a substituent, or the like; X1 represents a group represented by the formula -C(=O)-NH- or the like; E represents a furyl group, a thienyl group or a phenyl group; with the proviso that A1 may have one to three substituents, and E has one of two substituents] or a salt thereof or hydrates thereof.
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Page/Page column 63
(2008/06/13)
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- INDOLE DERIVATIVES
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The invention concerns indole derivatives of Formula (I) or pharmaceutically-acceptable salts thereof, wherein each of Ring A, m, R1, R2, n, R3 and G1 has any of the meanings defined hereinbefore in the description; processes for their preparation, pharmaceutical compositions containing them and their use in therapy, for example in the treatment of disease mediated by a PI3K enzyme and/or a mTOR kinase.
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Page/Page column 80
(2008/06/13)
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- NOVEL ANTIFUNGAL AGENT COMPRISING HETEROCYCLIC COMPOUND
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The present invention provides an antifungal agent represented by the formula: [wherein A1 represents a 3-pyridyl group which may have a substituent, a quinolyl group which may have a substituent, or the like; X1 represents a group represented by the formula -NH-C(=O)-, a group represented by the formula -C(=O)-NH-, or the like; E represents a furyl group, a thienyl group, a pyrrolyl group, a phenyl group, a pyridyl group, a tetrazolyl group, a thiazolyl group or a pyrazolyl group; with the proviso that A1 may have 1 to 3 substituents, and E has one or two substituents].
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Page/Page column 68; 71
(2010/11/08)
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- SYNTHESIS
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The present invention provides a novel substituted azaindoline intermediate of formula (I) and a method for its synthesis. The novel substitued azaindoline intermediate (I) is provided for use in the manufacture of 5-substituted 7-azaindolines and 5-substituted 7-azaindoles.
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Page 48; 50-51
(2010/02/08)
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- Thrombin inhibitors
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Compounds of the invention are useful in inhibiting thrombin and associated thrombotic occlusions having the following structure: or a pharmaceutically acceptable salt thereof, wherein b is NY or O; c is CY2or N; d is CY3or N; e is CY4or N; f is CY5or N; g is CY6or N; Y4, Y5, and Y6are independently hydrogen, C1-4alkyl, or halogen; Y1and Y2are independently hydrogen, C1-4alkyl, C3-7cycloalkyl, halogen, NH2, OH or C1-4alkoxy, and Y3is hydrogen, C1-4alkyl, C3-7cycloalkyl, halogen, —CN, NH2, OH or C1-4alkoxy; A is and W, W1, R1, R3, R4, R5, X and Z are defined in the specification.
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- THROMBIN INHIBITORS
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Compounds of the invention are useful in inhibiting thrombin and associated thrombotic occlusions having the following structure: or a pharmaceutically acceptable salt thereof, wherein b is N Y 1 or O; c is CY 2 or N; d is CY 2; e is CY 1 or N; f is CY 1 or N; g is CY 1 or N; Y 1 is hydrogen, C 1-4 alkyl, or halogen; Y 2 is hydrogen, C 1-4 alkyl, C 3-7 cycloalkyl, halogen, NH 2, OH or C 1-4 alkoxy;A is and W, X, Z, R 3, R 4 and R 5 are defined in the specification.
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