4998-07-6Relevant academic research and scientific papers
Method for preparing 6-nitroveratric acid from veratric acid in micro-channel reactor
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Paragraph 0005; 0027-0029; 0030-0032; 0033-0035; 0036-0038, (2021/05/19)
The invention provides a method for preparing 6-nitroveratric acid from veratric acid through a micro-channel reactor, aiming at solving the problems of low product yield, low purity and the like caused by large dilute nitric acid usage amount, difficulty in heat release control, much acidic wastewater, low production efficiency and more reaction ectopic nitration products in the existing method for preparing 6-nitroveratric acid through nitration. The invention provides the method for preparing 6-nitroveratric acid from veratric acid through the micro-channel reactor. According to the method, acetic acid is used as a solvent, veratric acid and concentrated nitric acid are used as raw materials, the reaction is performed in the micro-channel reactor, continuous production is realized, reaction heat release is easy to control, the production period is greatly shortened, the yield of 6-nitroveratric acid can reach 85% or above, and the purity of 6-nitroveratric acid can reach 99% or above.
Design, synthesis and biological evaluation of novel N-sulfonylamidine-based derivatives as c-Met inhibitors via Cu-catalyzed three-component reaction
Fang, Sen-Biao,Li, Hui-Jing,Nan, Xiang,Wu, Rui,Wu, Yan-Chao,Zhang, Jing,Zhang, Zhi-Zhou
, (2020/06/04)
In our continuing efforts to develop novel c-Met inhibitors as potential anticancer candidates, a series of new N-sulfonylamidine derivatives were designed, synthesized via Cu-catalyzed multicomponent reaction (MCR) as the key step, and evaluated for their in vitro biological activities against c-Met kinase and four cancer cell lines (A549, HT-29, MKN-45 and MDA-MB-231). Most of the target compounds showed moderate to significant potency at both the enzyme-based and cell-based assay and possessed selectivity for A549 and HT-29 cancer cell lines. The preliminary SAR studies demonstrated that compound 26af (c-Met IC50 = 2.89 nM) was the most promising compound compared with the positive foretinib, which exhibited the remarkable antiproliferative activities, with IC50 values ranging from 0.28 to 0.72 μM. Mechanistic studies of 26af showed the anticancer activity was closely related to the blocking phosphorylation of c-Met, leading to cell cycle arresting at G2/M phase and apoptosis of A549 cells by a concentration-dependent manner. The promising compound 26af was further identified as a relatively selective inhibitor of c-Met kinase, which also possessed an acceptable safety profile and favorable pharmacokinetic properties in BALB/c mouse. The favorable drug-likeness of 26af suggested that N-sulfonylamidines may be used as a promising scaffold for antitumor drug development. Additionally, the docking study and molecular dynamics simulations of 26af revealed a common mode of interaction with the binding site of c-Met. These positive results indicated that compound 26af is a potential anti-cancer candidate for clinical trials, and deserves further development as a selective c-Met inhibitor.
A preparation method of gefitinib (by machine translation)
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, (2019/05/16)
The present invention relates to organic chemical and medical technology field, in particular relates to a preparation method of gefitinib. The present invention provides a preparation method of gefitinib, obtained by formula I compounds, the formula I compound preparation method comprises the following steps: nitration reaction, oxidation reaction, selective demethylation reaction, reduction reaction, a cyclization reaction, phenolic hydroxyl acetylation reaction. The present invention provides a preparation method can at the same time reducing the cost, it is easy for the refined purification, easy preparation and control of related impurities, the overall preparation process routes are greatly optimized, is suitable for industrial scale production. (by machine translation)
A 3, 4 - dihydro -7 - methoxy -4 - [...] -6 - ethoxylate ester preparation method (by machine translation)
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, (2019/05/16)
The present invention relates to organic chemical and medical technology field, in particular to a 3, 4 - dihydro - 7 - methoxy - 4 - [...] - 6 - ethoxylate ester preparation method. The present invention provides a gefitinib 3, 4 - dihydro - 7 - methoxy - 4 - [...] - 6 - ethoxylate ester preparation method comprises the following steps: nitration reaction, oxidation reaction, selective demethylation reaction, reduction reaction, a cyclization reaction, phenolic hydroxyl acetylation reaction. Preparation method provided by the invention can at the same time reducing the cost, it is easy for the refined purification, easy preparation and control of related impurities, the overall preparation process routes are greatly optimized, is suitable for industrial scale production. (by machine translation)
Synthesis and pharmacological evaluation of 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives as sigma-2 receptor ligands
Sun, Yu-Tong,Wang, Gui-Fei,Yang, Yi-Qiu,Jin, Fujun,Wang, Yifei,Xie, Xiao-Yang,Mach, Robert H.,Huang, Yun-Sheng
, p. 227 - 237 (2018/02/14)
Increasing evidences have implicated that sigma-2 receptor is a biomarker and significantly over-expressed in many proliferative cancer cells with no or low expression in normal cells. Sigma-2 receptor selective ligands have been successfully used as valuable tools to study its pharmacological functions, tumor imaging, and cancer therapeutics or adjuvants. 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinolinylalkyl benzamides are among a few categories of structures that have demonstrated high affinities and selectivities for sigma-2 receptor and been used extensively as study tools in various tumor imaging and therapy. As a continuous effort, we have synthesized a new series of 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives and evaluated their affinities for both sigma-1 and sigma-2 receptors. Most of these newly developed analogs showed good to excellent binding affinities for sigma-2 receptor with no or low affinities for sigma-1 receptor. In particular, compounds 3b, 3e, 4b, and 4e demonstrated Ki values of 5–6 nM affinities and excellent selectivities for sigma-2 receptor. In addition, these analogs also demonstrated moderate anticancer activities against human liver Huh-7 tumor cells and human esophagus KYSE-140 cancer cells. But their cytotoxicities seem not to be correlated with their sigma-2 receptor affinities.
Tetrahydroisoquinoline derivatives preparation and application of (by machine translation)
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Paragraph 0121; 0122; 0123, (2018/09/21)
The invention mainly relates to a series of containing tetrahydroisoquinoline structure the synthesis of the compounds and in the medical field of application. Specifically, the invention relates to a series of tetrahydroisoquinoline structure compound, it can inhibit the polymerization of A β, antagonizing A β O in combination and in nerve cells caused by the cytotoxic, therapeutic or improve AD has application prospect. (by machine translation)
Studies on the interactions of 5-R-3-(2-pyridyl)-1,2,4-triazines with arynes: inverse demand aza-Diels-Alder reaction versus aryne-mediated domino process
Kopchuk, Dmitry S.,Nikonov, Igor L.,Khasanov, Albert F.,Giri, Kousik,Santra, Sougata,Kovalev, Igor S.,Nosova, Emiliya V.,Gundala, Sravya,Venkatapuram, Padmavathi,Zyryanov, Grigory V.,Majee, Adinath,Chupakhin, Oleg N.
, p. 5119 - 5135 (2018/07/29)
The interactions between substituted 5-R-3-(pyridyl-2)-1,2,4-triazines with in situ generated substituted aryne intermediates have been studied. The reaction afforded either inverse demand (ID) aza-Diels-Alder products or 1,2,4-triazine ring rearrangement (domino) products as major ones depending on the nature of both the substituents at the C5 position of the 1,2,4-triazine core or in the aryne moiety. The structures of the key products were confirmed based on X-ray data. Based on the density functional theoretical (DFT) studies of the Diels-Alder transition state geometries, the influence of the nature of arynes on the direction of the 1,2,4-triazine transformation has been proposed.
Design and discovery of quinazoline- and thiourea-containing sorafenib analogs as EGFR and VEGFR-2 dual TK inhibitors
Sun, Shaofeng,Zhang, Jingwen,Wang, Ningning,Kong, Xiangkai,Fu, Fenghua,Wang, Hongbo,Yao, Jianwen
, (2018/01/03)
Both EGFR and VEGFR-2 play a critical role in tumor growth, angiogenesis and metastasis, and targeting EGFR and VEGFR-2 simultaneously represents a promising approach to cancer treatment. In this work, a series of novel quinazoline- and thiourea-containing sorafenib analogs (10a–v) were designed and synthesized as EGFR and VEGFR-2 dual TK inhibitors. Their in vitro enzymatic inhibitory activities against EGFR and VEGFR-2, and antiproliferative activities against HCT-116, MCF-7 and B16 cell lines were evaluated and described. Most of the compounds showed potent activities against both cell lines and TK kinases. Compounds 10b and 10q which exhibited the most potent inhibitory activities against EGFR (IC50 = 0.02 μM and 0.01 μM, respectively), VEGFR-2 (IC50 = 0.05 μM and 0.08 μM, respectively), and good antiproliferative activities, also displayed competitive anti-tumor activities than sorafenib in vivo by B16 melanoma xenograft model test.
A pharmaceutical intermediate 3, 4 - dimethoxy -6 - nitro benzoic acid (by machine translation)
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Paragraph 0006; 0009-0014, (2018/07/30)
Abstract Drugs intermediates 3,4-dimethoxy-6-nitrobenzoic acid synthesis method, comprises the following steps: the reaction vessel was added 3 mol 5 2-bromo-3,4-dimethoxy-6-aminoacetophenone solution and 6-8 mol 1,5-pentanediol, controlled the stirring speed at 210-250 rpm, kept for 30-40 min, added 600 ml potassium carbonate solution, adjusted the pH to 8-9, increased the solution temperature to 60-70'C, added 3-5 mol nickel trioxide, continued to react for 30-40 min, added hydrogen sulfate potassium solution, adjusted the pH to 2-3, reduced the 10 solution temperature to 10-15 C, washed with sodium sulfate solution, washed with methyl cyclohexanone solution, washed with 1-methyl naphthalene solution, recrystallizated in 2-methyl-3-pentanol solution, dehydrated with dehydration, obtained the product 3,4 - dimethoxy-6-nitrobenzoic acid.
Erlotinib derivative with antitumor activity, and preparation method and application thereof
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Paragraph 0032; 0033; 0034, (2017/08/29)
The invention discloses an erlotinib derivative with antitumor activity, and a preparation method and application thereof, and belongs to the technical field of synthesis of antitumor active medicine. The method has the main technical scheme that the erlotinib derivative with antitumor activity has a structure formula shown as the accompanying drawing, wherein R is phenyl, p-methylphenyl, m-nitrophenyl, o-chlorphenyl or o-hydroxy benzon phenyl. The invention also discloses a concrete synthesis process of the erlotinib derivative with antitumor activity and application of the erlotinib derivative with antitumor activity to preparation of liver cancer treatment medicine. The erlotinib molecules are modified and are structurally connected with a series of different 1,2,3-triazole groups; the synthesized erlotinib derivative is subjected to anti-tumor activity test; the test result shows that the compound has high inhibition activity on liver cancer HepG2 cells.
