- A EGFR molecule targeting anti-tumor pharmaceutical preparation method
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The invention relates to a preparation method for an EGFR molecule targeting antitumor drug, and provides a preparation method for (E)-N-[4-(3-acetylene phenyl)amino-3-cyan-7-ethoxy-6-quinolyl]-4-(dimethyl amino)-2-butylene amide. The preparation method comprises the following steps: N-(4-chloro-3-cyan-7-ethoxy quinoline-6-yl) acetamide (a compound II) and 3-aminophenylacetylene (a compound III) are subjected to a substitution reaction, and a compound IV is obtained; under an acidic or alkaline condition, the compound IV is subjected to a hydrolysis reaction, and 3-cyan-6-amino-7-ethoxy-4-(3-acetenyl anilino) quinoline (a compound V) is obtained; after trans-4-dimethylaminocrotonic acid hydrochloride (a compound VI) and an acylation reaction reagent is subjected to an acylation reaction, the product and 3-cyan-6-amino-7-ethoxy-4-(3-acetenyl anilino) quinoline (the compound V) are subjected to condensation reaction, and the finished product is obtained. The method is advantageous in that raw materials are easily available, the technology is concise, the production cost is low, and the method is economical and environmentally friendly and is suitable for industrial production.
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Paragraph 0027-0029
(2019/05/06)
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- Chlorobenzene-pyridine compounds and application thereof
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The invention relates to chlorobenzene-pyridine compounds and an application thereof. The compounds can be used for preparing a Smoothened protein inhibitor and a drug for resisting adenocarcinoma andesophagus cancer and have the structure in the general formula (I) shown in the description, wherein X is selected from the structure shown in the description, R1 is selected from H or the structureshown in the description, and R2 is selected from the structure shown in the description.
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Paragraph 0112; 0123; 0124; 0125
(2018/04/01)
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- Synthetic method for (2Z)-4-(dimethylamino)but-2-enoic acid hydrochloride
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The invention discloses a synthetic method for (2Z)-4-(dimethylamino)but-2-enoic acid hydrochloride. The synthetic method comprises the following steps: under an inert gas atmosphere, dissolving [bi(2,2,2-trifluoroethoxy)-phosphinyl]methyl acetate in organic solvent, adding lithium reagent, adding alkali solution, controlling the temperature to 0-30 DEG C, adding 2-(dimethylamino)acetaldehyde sulfite, and carrying out stirring reaction, carrying out acidification, extraction and column purification after reaction to obtain the (2Z)-4-(dimethylamino)but-2-enoic acid hydrochloride. The syntheticmethod has the advantages of convenience in operation and high yield, and industrial production can be realized.
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Paragraph 0026-0035
(2018/11/02)
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- QUINAZOLINE DERIVATIVE, PREPARATION METHOD THEREFOR, AND PHARMACEUTICAL COMPOSITION AND APPLICATION THEREOF
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Disclosed are a quinazoline derivative, a preparation method therefor, and a pharmaceutical composition and an application thereof. The present invention provides a compound represented by general formula I, a stereoisomer thereof and a pharmaceutical acceptable salt or a solvate thereof. The quinazoline derivative of the present invention has a unique chemical structure, is characterized by irreversibly inhibiting EGFR tyrosine kinase, has high biological activity, apparently improves the inhibiting effect on the EGFR tyrosine kinase, has quite strong tumor inhibiting effect on tumor cells and a transplantation tumor pathological model of animal tumors, and has good market developing prospects.
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Paragraph 0134; 0137
(2017/07/14)
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- A steps Hua Tini chemical synthesis method (by machine translation)
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The present invention provides a convenient steps Hua Tini chemical synthesis method, using the synthesis method adopted in the process of preparing steps Hua Tini cheap raw materials, is easy to obtain, and saves the production cost, and the adoption of the synthesis method of the high yield of the product, the whole in the preparation process of mild reaction conditions, the atom economy is high. (by machine translation)
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Paragraph 0057; 0058; 0059
(2017/03/25)
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- Design, synthesis and biological evaluation of WZ4002 analogues as EGFR inhibitors
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A series of thirty two anilinopyrimidines derived from WZ4002 has been synthesized and evaluated for percentage inhibition of six different EGFR kinases using LanthaScreen binding assay method (EGFR d746 – 750) or Z'LYTE assay method (EGFR-WT, EGFR d746 – 750, EGFR T790M, EGFR T790M L858R, EGFR C797S and EGFR T790M L858R C797S). Ortho-hydroxyacetamide 10 exhibited complete inhibition of all the six kinases at 10 μM. Against the triple mutant, EGFR T790M C797S L858R, compounds 9–12 exhibited complete inhibition at 10 μM and nearly complete inhibition at 1 μM. The target compounds were also evaluated using the MTT assay to determine their cytotoxic activity against human non-small cell lung cancer cells (PC9, PC9GR and H460) and mouse leukemic cells (Ba/F3 WT and Ba/F3T 3151). Overall, 7, 9–12, 30 and 31 were found to be the most potent compounds across all five cell lines.
- Romu, Aireen A.,Lei, Zining,Zhou, Bin,Chen, Zhe-Sheng,Korlipara, Vijaya
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supporting information
p. 4832 - 4837
(2017/10/06)
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- A trans-4-dimethylamino crotonic acid hydrochloride preparation method (by machine translation)
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A trans-4-dimethylamino crotonic acid hydrochloride preparation method, to N, N-dimethylamine base acetaldehyde bisulfite as the substrate, the phosphono acetic acid three diethlyl generating HWE reaction to obtain trans-4-dimethylamino crotonic acid hydrochloride. Through the preferred reaction conditions, the reaction to obtain HWE trans-4-dimethylamino crotonic acid hydrochloride. (by machine translation)
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Paragraph 0015; 0016; 0017; 0018; 0019; 0020; 0021-0023
(2016/10/27)
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- Preparation method for afatinib
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The invention provides a preparation method for afatinib. The preparation method comprises the following steps: subjecting trans-4-dimethylaminocrotonic acid hydrochloride (III) to chlorination so as to obtain trans-4-dimethylaminocrotonyl chloride hydrochloride (IV); and reacting the compound (IV) with N4-(3-chloro-4-fluoro-phenyl)-7-((S)-tetrahydrofuran-3-yl-oxy)quinazoline-4,6-diamine (V) so as to prepare afatinib (VI). Reaction equations are described in the specification.
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Paragraph 0024; 0025; 0026; 0027; 0028; 0029; 0030-0032
(2016/10/08)
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- Pyrazolopyrimidine derivative, preparation method, pharmaceutical composition and application
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The invention discloses a pyrazolopyrimidine derivative, a preparation method, a pharmaceutical composition and application. The invention provides the pyrazolopyrimidine derivative as shown in a formula I and stereoisomer or solvate or pharmaceutically acceptable salts or active metabolite or prodrug thereof. The pyrazolopyrimidine derivative as shown in the formula I has good inhibitory activity on Bruton's tyrosine kinase (Btk) and particularly has good in vitro and in vivo inhibitory activity on growth of tumor cells, and a good marketization prospect is achieved. Please see the formula I in the description.
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Paragraph 0249; 0250; 0253
(2017/07/19)
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- PYRAZOLYLAMINOPURINES AS ITK INHIBITORS
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Provided are pyrazolylaminopurine compounds that are inhibitors of ITK kinase, compositions containing these compounds and methods for treating diseases mediated by ITK kinase. In particular, provided are compounds of Formula I or II, stereoisomers, tauto
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Page/Page column 93
(2016/11/07)
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- PROCESS FOR THE PREPARATION OF 4-DIMETHYLAMINOCROTONIC ACID
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The present invention provides a process for the preparation of 4- dimethylaminocrotonic acid of Formula (II) or its salts, which is used as an intermediate for the preparation of afatinib or its salts.
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Page/Page column 7
(2015/12/24)
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- PROCESS FOR THE MANUFACTURE OF (E)-4-N,N-DIALKYLAMINO CROTONIC ACID IN HX SALT FORM AND USE THEREOF FOR SYNTHESIS OF EGFR TYROSINE KINASE INHIBITORS
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The present invention is directed to an efficient process for the manufacture of (E)-4-N,N-dialkylamino crotonic acid in HX salt form of formula I wherein R1 and R2 independently denote C1-3-alkyl groups and X? denotes an acid anion, such as the chloride, bromide, tosylate, mesylate or trifluoroacetate anion, with high quality, and a process for synthesis of EGFR tyrosine kinase inhibitors with heterocyclic quinazoline, quinoline or pyrimidopyrimidine core structure, using the acid addition salt I and activated derivatives thereof as intermediates.
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Paragraph 0041; 0042
(2015/07/15)
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- PROCESS FOR THE MANUFACTURE OF (E)-4-N,N-DIALKYLAMINO CROTONIC ACID IN HX SALT FORM AND USE THEREOF FOR SYNTHESIS OF EGFR TYROSINE KINASE INHIBITORS
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The present invention is directed to an efficient process for the manufacture of (E)-4-N,N- dialkylamino crotonic acid in HX salt form of formula I, wherein R1 and R2 independently denote C1-3-alkyl groups and Xˉ denotes an acid anion, such as the chloride, bromide, tosylate, mesylate or trifluoroacetate anion, with high quality, and a process for synthesis of EGFR tyrosine kinase inhibitors with heterocyclic quinazoline, quinoline or pyrimidopyrimidine core structure, using the acid addition salt I and activated derivatives thereof as intermediates.
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Page/Page column 18
(2015/07/16)
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- METHOD OF PREPARING AN ALKYLAMINE DERIVATIVE
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The present invention provides a method of preparing an alkylamine derivates which hardly generates impurities and enables mass production with high purity.
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Page/Page column 5-6
(2012/03/10)
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- SUBSTITUTED HETEROCYCLIC COMPOUNDS AS KINASES INHIBITORS AND METHOD OF USE THEREOF
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The present invention is directed to novel quinolines and quniazolines, their derivatives, pharmaceutically acceptable salts, solvates and hydrates thereof which are useful for the treatment of protein kinases mediated diseases and conditions. The compounds of this invention have a general Formula (I) wherein R1 to R11 and X are defined herein.
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Page/Page column 36
(2011/01/12)
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- SUBSTITUTED TRICYCLIC COMPOUNDS AND METHODS OF USE THEREOF
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This invention relates to novel compounds and processes for their preparation, methods of treating diseases, particularly cancer, comprising administering said compounds, and methods of making pharmaceutical compositions for the treatment or prevention of disorders, particularly cancer.
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Page/Page column 58
(2009/04/25)
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- Antineoplastic combinations
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This invention provides the use of a combination of CCI-779 and EKB-569 in the treatment of neoplasms.
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