5551-11-1Relevant articles and documents
Non-alkylator anti-glioblastoma agents induced cell cycle G2/M arrest and apoptosis: Design, in silico physicochemical and SAR studies of 2-aminoquinoline-3-carboxamides
Gu, Xiangyu,Liu, Jianwen,Ni, Xintong,Qi, Yingxue,Qian, Xuhong,Shao, Xusheng,Xu, Xiaoyong,Yuan, Pengtao
supporting information, (2021/09/22)
Malignant gliomas are the most common brain tumors, with generally dismal prognosis, early clinical deterioration and high mortality. Recently, 2-aminoquinoline scaffold derivatives have shown pronounced activity in central nervous system disorders. We herein reported a series of 2-aminoquinoline-3-carboxamides as novel non-alkylator anti-glioblastoma agents. The synthesized compounds showed comparable activity to cisplatin against glioblastoma cell line U87 MG in vitro. Among them, we found that 6a displayed good inhibitory activity against A172 and U118 MG glioblastoma cell lines and induced cell cycle arrest in the G2/M phase and apoptosis in U87 MG by flow cytometry analysis. Additionally, 6a displayed low cytotoxicity to several normal human cell lines. In silico study showed 6a had promising physicochemical properties and was predicted to cross the blood–brain barrier. Moreover, preliminary structure–activity relationships are also investigated, shedding light on further modifications towards more potent agents on this series of compounds. Our results suggest this compound has a promising potential as an anti-glioblastoma agent with a differential effect between tumor and non-malignant cells.
Exploiting excited-state aromaticity to design highly stable singlet fission materials
Fallon, Kealan J.,Budden, Peter,Salvadori, Enrico,Ganose, Alex M.,Savory, Christopher N.,Eyre, Lissa,Dowland, Simon,Ai, Qianxiang,Goodlett, Stephen,Risko, Chad,Scanlon, David O.,Kay, Christopher W. M.,Rao, Akshay,Friend, Richard H.,Musser, Andrew J.,Bronstein, Hugo
supporting information, p. 13867 - 13876 (2019/09/30)
Singlet fission, the process of forming two triplet excitons from one singlet exciton, is a characteristic reserved for only a handful of organic molecules due to the atypical energetic requirement for low energy excited triplet states. The predominant strategy for achieving such a trait is by increasing ground state diradical character; however, this greatly reduces ambient stability. Herein, we exploit Baird's rule of excited state aromaticity to manipulate the singlet-triplet energy gap and create novel singlet fission candidates. We achieve this through the inclusion of a [4n] 5-membered heterocycle, whose electronic resonance promotes aromaticity in the triplet state, stabilizing its energy relative to the singlet excited state. Using this theory, we design a family of derivatives of indolonaphthyridine thiophene (INDT) with highly tunable excited state energies. Not only do we access novel singlet fission materials, they also exhibit excellent ambient stability, imparted due to the delocalized nature of the triplet excited state. Spin-coated films retained up to 85% activity after several weeks of exposure to oxygen and light, while analogous films of TIPS-pentacene showed full degradation after 4 days, showcasing the excellent stability of this class of singlet fission scaffold. Extension of our theoretical analysis to almost ten thousand candidates reveals an unprecedented degree of tunability and several thousand potential fission-capable candidates, while clearly demonstrating the relationship between triplet aromaticity and singlet-triplet energy gap, confirming this novel strategy for manipulating the exchange energy in organic materials.
Iron promoted C3-H nitration of 2H-indazole: direct access to 3-nitro-2H-indazoles
Murugan, Arumugavel,Gorantla, Koteswar Rao,Mallik, Bhabani S.,Sharada, Duddu S.
supporting information, p. 5113 - 5118 (2018/07/29)
An efficient C3-H functionalization of indazole has been demonstrated. Notably, this method involves chelation-free radical C-H nitration on 2H-indazole. The radical mechanism was confirmed by control experiments and quantum chemical calculations. The synthetic utility has been proven by the synthesis of bio-relevant benzimidazoindazoles via reductive cyclization.
A 3 - amino -7 - chloroquinolin synthetic method (by machine translation)
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Paragraph 0045; 0046; 0066; 0067, (2018/09/26)
The invention provides a 3 - amino - 7 - chloroquinolin synthetic method. Synthesis method of the invention, in order to 4 - chloro - 1 - methyl - 2 - nitrobenzene as the raw materials, and N, N - dimethyl formamide dimethyl acetal to hydroformylation reaction to produce 4 - chloro - 2 - nitrobenzaldehyde, with 3, 3 - diethyl oxygen radical propionic acid ethyl ester to ring-closure reaction to produce 7 - chloro - 3 - quinoline carboxylic acid ethyl ester, under basic condition to produce 7 - chloro - 3 - quinoline carboxylic acid, with the azido diphenyl phosphate through Curtius rearrangement reaction to 3 - tert-butoxycarbonyl amino - 7 - chloroquinolin, finally through takes off uncle butoxycarbonyl to obtain 3 - amino - 7 chloroquinolin. The invention of 3 - amino - 7 - chloroquinolin synthetic method, the synthetic route is simple, reasonable process, low material cost, simple and easy to obtain, operation and after treatment is convenient, the total yield is high, easy to enlarge, can be large-scale production of 3 - amino - 7 - chloroquinolin. (by machine translation)
A depression drug impurity of preparing method (by machine translation)
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, (2018/09/11)
The invention relates to a depression drug impurity of preparing method, it comprises the following steps: (a) the high sodium iodate, water and mixed DMF; (b) is poured into ice water, adjusting pH with alkali and layered extraction, purification to obtain compound 4; in the 120 - 150 °C reaction after column chromatography separation to obtain compound 5; (c) the compound 3 and said compound 5 by adding ethylene glycol dimethyl ether, in the ice water bath under the conditions of the adding sodium hydride to, heating up to 40 - 60 °C reaction 20 - 40 minutes, further heating up to reflux; (d) the compound 6 with the [...] catalyst, morpholine, methanol and ethanol are mixed, the reaction is carried out in a hydrogen atmosphere, filtered [...] filtrate to obtain compound 7; (e) the compound 7 with formic acid, a sodium mixed, heated to 100 - 120 °C refluxing reaction; (g) the compound 10 in toluene soluble, in an inert gas atmosphere by adding sodium hydride, temperature reaction. This can obtain the high purity of the depression drug impurity isomer, for impurity accurate control. (by machine translation)
Preparation method of impurity isomer key intermediate of anti-depressive drug
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, (2018/09/11)
The invention relates to a preparation method of an impurity isomer key intermediate of an anti-depressive drug. The preparation method comprises the following steps: (a) mixing sodium periodate, water and DMF (Dimethylformamide); (b) pouring in ice water, adjusting pH with an alkaline solution, extracting by layers, purifying to obtain a compound 4, and performing column chromatography isolationafter reacting at 120 to 150 DEG C to obtain a compound 5; (c) adding the compound 3 and the compound 5 into 1,2-dimethoxyethane, adding sodium hydride under the condition of ice water bath, heating to 40 to 60 DEG C for reacting for 20 to 40 minutes, and heating and refluxing; (d) mixing the compound 6 with a rhodium carbon catalyst, morpholine, methanol and ethanol, reacting under a hydrogen atmosphere, and performing suction filtration and spin drying on filtrate to obtain a compound 7; (e) mixing the compound 7 with formic acid and sodium formate, and heating to 100 to 120 DEG C for refluxreaction; (f) adding anhydrous K2CO3,Cu powder and CuBr, performing reaction under the protection of insert gas at the temperature of 150 to 180 DEG C to obtain a compound 9; cooling to 30 to 60 DEGC, adding NaOH solution to perform reaction, filtering, and purfying to obtain a compound 10.. By adopting the preparation method, a high-purity impurity isomer of the anti-depressive drug can be obtained for accurate control of impurities.
Preparation method of chloronitrophenyl intermediate serving as impurity isomer of medicine for treating depression
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, (2018/11/22)
The invention relates to a preparation method of a chloronitrophenyl intermediate serving as an impurity isomer of medicine for treating depression. The method includes the following steps that a, sodium periodate, water and DMF are mixed, then a DMF solution of a compound 2 is added for a reaction, and after the reaction, a filtrate is taken and purified to obtain a compound 3; b, 2-bromo-4-chlorotoluene, N-bromosuccinimide, dibenzoyl peroxide and carbon tetrachloride are mixed, stirred, heated to 80-100 DEG C for a reaction and then poured into ice water, the pH is adjusted with lye, and layered extraction and purification are conducted to obtain a compound 4; c, the compound 3 and a compound 5 are added into glycol dimethyl ether, sodium hydride is added under the condition of an ice water bath, the temperature is raised to 40-60 DEG C for a reaction for 20-40 minutes, then the temperature is raised for reflux, after the reaction is completed, water and ethyl acetate are added in avolume ratio of 1:1, and solid is precipitated, subjected to suction filtration and dried to obtain a compound 6. In this way, the nitrophenyl intermediate with high purity can be obtained to be usedfor subsequent preparation of the high-purity and high-yield impurity isomer of medicine for treating depression.
Enamine compound synthesis method and aromatic aldehydes synthetic method of the compound (by machine translation)
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Paragraph 0064; 0065; 0069; 0070; 0075; 0084; 0085; 0086, (2017/12/09)
The invention provides a method for synthesis of a enamine compound and aromatic aldehydes synthetic method of the compound. Enamine compound of synthetic method comprises the starting raw materials with A N, N - dimethyl formamide dimethyl acetal to form a mixed solution; and the mixed solution is continuously fed into the continuous reactor in the alkene amination reaction to obtain the enamine compound B, and alkene amination reaction in continuous enamine compound discharged from the continuous reactor in B; A starting material of formula (1) shown in the structural formula of, enamine compound B formula (2) shown in the structural formula. The reaction of the raw material of the mixed solution and continuously fed into the reactor by way of the alkene amination reaction alkene amination reaction of continuous, then also the continuous production of aromatic aldehyde compound, shortens the reaction time, the reaction efficiency is improved. The continuous reaction method can be stopped at any time according to the actual conditions the reaction or the termination of the reaction, after-treatment can also be based on the need to batch processing or merging processing, is convenient and simple. (by machine translation)
Synthetic process of aromatic acetaldehyde compound
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Paragraph 0063; 0067; 0068; 0069; 0087, (2017/11/30)
The invention provides a synthetic process of an aromatic acetaldehyde compound; the synthetic method includes forming a mixed solution via starting material A with N,N-dimethylformamide dimethyl acetal; continuously feeding the mixed solution into a continuous reactor to carry out enamination reaction to obtain enamide B, and discharging the enamide B from the continuous reactor during enamination reaction; preparing aromatic acetaldehyde compound C with the enamide B, wherein the starting material A has a structural formula shown as formula (1), the enamide B has a structural formula shown as formula (2), and the aromatic acetaldehyde compound C has a structural formula shown as formula (3). By continuously feeding the mixed solution of reaction materials into the reactor to carry out enamination reaction, enamination reaction is continuously performed; continuous production of aromatic acetaldehyde compounds is achieved, reaction time is shortened, and reaction efficiency is improved.
Stable TEMPO and ABNO Catalyst Solutions for User-Friendly (bpy)Cu/Nitroxyl-Catalyzed Aerobic Alcohol Oxidation
Steves, Janelle E.,Stahl, Shannon S.
, p. 11184 - 11188 (2015/11/18)
Two solutions, one consisting of bpy/TEMPO/NMI and the other bpy/ABNO/NMI (bpy =2,2′-bipyridyl; TEMPO = 2,2,6,6-tetramethylpiperidine N-oxyl, ABNO = 9-azabicyclo[3.3.1]nonane N-oxyl; NMI = N-methylimidazole), in acetonitrile are shown to have good long-term stability (≥1 year) under air at 5 °C. The solutions may be combined in appropriate quantities with commercially available [Cu(MeCN)4]OTf to provide a convenient catalyst system for the aerobic oxidation of primary and secondary alcohols.
