- Preparation method of quinazolinyl butylene amide compound
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The invention discloses a preparation method of a quinazolinyl butylene amide compound, which effectively reduces the generation of impurities in the synthesis process by selecting a proper mixed alkali system and using a mixture of 1, 5-diaza-bicyclo [4.3. 0] nonyl-5-ene and potassium hydroxide, avoids the additional generation of degraded impurities in the medicine storage process, and accurate control over impurity generation and degradation is achieved.
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Paragraph 0045-0049; 0053-0057; 0060-0064; 0067-0071; ...
(2021/07/17)
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- Substituted quinoline-8-carbonitrile derivatives having androgen receptor degradation activity and uses thereof
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The present disclosure relates to novel compounds, pharmaceutical compositions containing such compounds, and their use in prevention and treatment of cancer and related diseases and conditions. In some embodiments, the compounds disclosed herein exhibit androgen receptor degradation activity.
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Page/Page column 99-100
(2020/11/23)
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- HETEROCYCLIC INHIBITORS OF TYROSINE KINASE
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The present disclosure relates to heterocyclic compounds and methods which may be useful as inhibitors of HER2 or EGFR for the treatment or prevention of disease, including cancer.
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Paragraph 0301-0303
(2020/11/03)
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- PYRROLO-AROMATIC HETEROCYCLIC COMPOUND, PREPARATION METHOD THEREFOR, AND MEDICAL USE THEREOF
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The present invention relates to pyrrolo-aromatic heterocyclic compounds, a preparation method therefor and medical use thereof. Particularly, the present invention relates to a compound represented by formula I, a preparation method therefor, a pharmaceu
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Paragraph 0135
(2019/11/11)
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- Design, synthesis, antiproliferative activity and docking studies of quinazoline derivatives bearing 2,3-dihydro-indole or 1,2,3,4-tetrahydroquinoline as potential EGFR inhibitors
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Eight series of quinazoline derivatives bearing 2,3-dihydro-indole or 1,2,3,4-tetrahydroquinoline were designed, synthesized and evaluated for the IC50 values against three cancer cell lines (A549, MCF-7 and PC-3). Most of the forty nine target compounds showed excellent antiproliferative activity against one or several cancer cell lines. The compound 13a showed the best activity against A549, MCF-7 and PC-3 cancer cell lines, with the IC50 values of 1.09 ± 0.04 μM, 1.34 ± 0.13 μM and 1.23 ± 0.09 μM, respectively. Eight selected compounds were further selected to evaluated for the inhibitory activity against EGFR kinase. Three of them showed equal activity against EGFR kinase to positive control afatinib. AnnexinV-FITC, propidium iodide (PI) double staining and acridine orange single staining results indicated that the compound 13a could induce apoptosis of human lung cancer A549 cells.
- OuYang, Yiqiang,Zou, Wensheng,Peng, Liang,Yang, Zunhua,Tang, Qidong,Chen, Mengzi,Jia, Shuang,Zhang, Hong,Lan, Zhou,Zheng, Pengwu,Zhu, Wufu
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- Quinazoline compounds and preparation method thereof as well as application of quinazoline compounds to preparation of tyrosine-kinase inhibitor
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The invention relates to a novel quinazoline compound and a method for preparing a quinazoline crotyl compound for treating or preventing various indications relating to EGFR (Epidermal Growth Factor Receptor) and HER (HER Human Epidermal Growth Factor Receptor)2 kinase functions. The method comprises the following steps: firstly, enabling a raw material with an amino group to react with diethylphosphonoacetic acid and N,N'-carbonyldiiazole in a solvent at the temperature of 25 to 50DEG C, and converting the amino group in the raw material into diethylacetoacetamido; secondly, enabling an intermediate to react with N,N'-disubstituted acetaldehyde in the solvent at the temperature of 30DEG C below zero and 20DEG C below zero in the presence of alkaline matters to generate a target compound. According to the method, the target product with the purity greater than 98 percent can be obtained by adopting simple route and simple post treatment; the total yield of the target product is as high as 74 percent; besides, by means of the method disclosed by the invention, kilogram-target products can be successfully prepared, and batch production is easily realized.
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Paragraph 0075; 0079
(2017/10/26)
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- Method for preparing Neratinib
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The invention relates to a preparation method for neratinib. Specifically, N-[4-[[3-chloro-4-(2-pyridylmethoxy)phenyl]amino]-3-cyano-7-ethoxy-6-quinolyl]-2-diethyl phosphate-acetamide reacts with 2,2-diethoxy-N,N-dimethylethylamine or 2-(dimethylamino)acetaldehyde in the presence of a lithium salt and an alkali to produce neratinib. The method provided by the invention has the advantages of high yield, mild reaction conditions, usage of common and commercially available reagents, a low price, suitability for industrial production and good economic prospects.
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Paragraph 0023
(2017/04/03)
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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 0038
(2015/07/15)
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- Kinetics and mechanism of oxidation of N,N-dimethylethanolamine by diperiodatocuprate(III) complex in alkaline medium
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The kinetics and mechanisms of the oxidation of N,N-dimethylethanolamine (DMEA) by diperiodatocuprate(III) (DPC) in aqueous alkaline medium was studied with spectrophotometry in a temperature range of 293.2-313.2 K. The reaction shows first order dependence on [DPC] and fractional order with respect to [N,N-dimethylethanolamine]. The observed rate constant (kobs) decreased with increasing [IO4-] and increased with increasing [OH-]. Increasing ionic strength of the medium decreased the rate. Free radicals were observed in the process of reaction. A mechanism involving the diperiodatocuprate(III)) as the reactive species of the oxidant has been proposed. The rate constants of the rate-determining step and the activation parameters were calculated.
- Shan, Jinhuan,Wang, Xiaoqian,Shen, Haixia
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experimental part
p. 180 - 182
(2011/11/14)
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- Discovery and optimization of a series of quinazolinone-derived antagonists of CXCR3
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A series of quinazolinone-derived inhibitors of the CXCR3 receptor have been synthesized and their affinity for the receptor evaluated. Compounds were evaluated in a 125I-IP10 displacement assay and in in vitro cell migration assays to IP10, IT
- Johnson, Michael,Li, An-Rong,Liu, Jiwen,Fu, Zice,Zhu, Liusheng,Miao, Shichang,Wang, Xuemei,Xu, Qingge,Huang, Alan,Marcus, Andrew,Xu, Feng,Ebsworth, Karen,Sablan, Emmanuel,Danao, Jay,Kumer, Jeff,Dairaghi, Dan,Lawrence, Chris,Sullivan, Tim,Tonn, George,Schall, Thomas,Collins, Tassie,Medina, Julio
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p. 3339 - 3343
(2008/02/11)
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- Methods of enhancing renal uptake of oligonucleotides
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2′-O-Modified ribosyl nucleosides and modified methods containing such nucleosidic monomers are disclosed. Methods are disclosed that have increased binding affinity as shown by molecular modeling experiments. Methods are also disclosed for enhancing the renal uptake of oligomeric compounds as shown using a two-step HRP imunohistochemistry assay. The 2′-O-modified nucleosides of the invention include ring structures that position the sugar moiety of the nucleosides preferentially in 3′ endo geometries.
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- 2′-O-aminoethyloxyethyl-modified oligonucleotides
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2′-O-Modified ribosyl nucleosides and modified oligomeric compounds containing such nucleosidic monomers are disclosed. Oligomeric compounds are disclosed that have increased binding affinity as shown by molecular modeling experiments. The 2′-O-modified nucleosides of the invention include ring structures that position the sugar moiety of the nucleosides preferentially in 3′ endo geometries.
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- DEHYDROGENATION OF SUBSTITUTED ALCOHOLS TO ALDEHYDES ON ZINC OXIDE-CHROMIUM OXIDE CATALYSTS
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Sixteen primary alcohols of the structure RCH2OH (R = CH3, C2H5, (CH3)2CH, (CH3)3CCH2, HOCH2, CH3OCH2, C6H5, C6H5CH2, C6H5OCH2, ClCH2, BrCH2, F3C, CNCH2, (CH3)2NCH2, (C2H5)2NCH2 and tetrahydrofurfuryl) were explored for the possibility of obtaining the corresponding aldehydes by dehydrogenation on solid catalysts.Various catalysts were tested and two zinc oxide-chromium oxide catalysts were selected for further work because their activity and selectivity was satisfactory; moreover, the selectivity could be improved by addition of sodium into the catalysts and of water into the feed.The reaction was performed in the temperature range 250 - 450 deg C and at atmospheric pressure. 2-Chloroethanol, 2-bromoethanol, ethylene glycol, 2-cyanoethanol and 2-(N,N-diethylamino)ethanol decomposed and deactivated the catalyst.The other alcohols were studied from the point of kinetics of dehydrogenation, which was described by a Langmuir-Hinshelwood type rate equation (3), and of substituent effects on rate, which were correlated by Taft equation (1) with the slope ρ* = -1.46.The preparative value of catalytic dehydrogenation for obtaining substituted aldehydes was confirmed by prolonged runs and isolation of the aldehydic product by distillation using as the feeds 2-methoxyethanol and 2-(N,N-dimethylamino)ethanol, respectively.
- Gulkova, Daniela,Kraus, Milos
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p. 2215 - 2226
(2007/10/02)
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- H2-Antihistaminics, XXXII: Synthesis and H2-Antagonistic Activity of N--1,3,4-oxadiazol-2-amines
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The synthesis and H2-antagonistic activity of N--1,3,4-oxadiazol-2-amine and its 5-substituted derivatives are reported.
- Kraemer, Irene,Schunack, Walter
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p. 1091 - 1098
(2007/10/02)
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