1131-62-0Relevant articles and documents
Design, Synthesis and Biological Evaluation of Novel α-Acyloxycarboxamide-Based Derivatives as c-Met Inhibitors
Feng, Yu-juan,Ren, Yu-Lin,Zhao, Li-Ming,Xue, Guo-Qiang,Yu, Wen-Hao,Yang, Jia-Qi,Liu, Jun-Wei
, p. 2241 - 2250 (2021)
Dysregulated HGF/c-Met signalling has been associated with many human cancers, poor clinical outcomes, and even resistance acquisition to some approved targeted therapies. As such, c-Met kinase has emerged as an attractive target for anticancer drug discovery. Herein, a series of 6,7-disubstitued-4-(2-fluorophenoxy)quinoline derivatives bearing α-acyloxycarboxamide moiety were designed, synthesized via Passerini reaction as the key step, and evaluated for their in vitro biological activities against c-Met kinase and five selected cancer cell lines. The preliminary structure-activity relationship demonstrated that α-acyloxycarboxamide as the 5-atom linker maintained the potent antitumor potency. Among these compounds, compound 25s (c-Met IC50 = 4.06 nmol/L) was identified as the most promising lead compound and displayed the most potent antiproliferative activities against A549, HT-29 and MDA-MB-231 cell lines with IC50 of 0.39, 0.20, and 0.58 μmol/L, which were 1.3-, 1.4- and 1.2-fold superior to foretinib, respectively. The further studies indicated that compound 25s can induce apoptosis of A549 cells and arrest efficiently the cell cycle distribution in G2/M phase of A549 cells. Moreover, compound 25s can also inhibit c-Met phosphorylation in A549 cells by a dose-dependent manner. Collectively, these results indicated that compound 25s could be a potential anticancer lead compound deserving for further development.
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Dominguez et al.
, p. 5150 (1954)
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Lignin peroxidase catalysed oxidation of 4-methoxymandelic acid. The role of mediator structure
Baciocchi, Enrico,Gerini, Maria Francesca,Lanzalunga, Osvaldo,Mancinelli, Simona
, p. 8087 - 8093 (2002)
A large number of substances have been tested as redox mediators in the LiP-catalysed oxidation of 4-methoxymandelic acid (4-MMA) to anisaldehyde. In some cases (i.e. thioanisole), the mediation efficiency is almost equal to the maximum value displayed by the natural mediator veratryl alcohol. The mediation efficiency is a function of the redox potential of the mediator and also appears to depend on the kinetic effectiveness with which the mediator is oxidised by the enzyme. In contrast, the lifetime of the mediator radical cation seems not to play any significant role, which would support the idea that the redox mediation is actually accomplished by a complex between the mediator radical cation and the enzyme.
Highly selective vapor-phase acylation of veratrole over H3PO4/TiO2-ZrO2: Using ethyl acetate as a green and efficient acylating agent
Javad Kalbasi, Roozbeh,Abbaspourrad, Alireza,Massah, Ahmad Reza,Zamani, Farzada
, p. 273 - 284 (2010)
A simple sol-gel method with and without surfactant was applied to prepare TiO2-ZrO2 mixed oxides containing Ti and Zr at a molar ratio of 1:1. Several catalysts containing w=15%-35% H3PO4 were set up using these mixed oxides. The physical and chemical properties of catalysts were investigated by BET, SEM and pyridine adsorption-desorption. The catalytic performance of each material was determined for the vapor-phase acylation of veratrole (1,2-dimethoxybenzene) to 3,4-dimethoxyacetophenone (3,4-DMAP), which was found to be the major product of the reaction of veratrole with ethyl acetate, with alkylated products being the minor products. 2,3-Dimethoxyacetophenone (2,3-DMAP) was not detected in the product stream. In the best experimental conditions, the alkylated products were less than 0.7%. This reaction may represent an environmentally friendly alternative to use the ethyl acetate as the acylating reagent. The feed molar ratios of veratrole/ethyl acetate were varied over a wide range of 0.1 to 1, and the optimum feed ratio of veratrole/ethyl acetate was 1:3. Space velocity employed in the veratrole acylation reported as WHSV (veratrole) was 1.2 h-1. The acylation reactions were carried out in the temperature range of 423 to 673 and the optimum H3PO4 content for acylation was w15%.
Structure-based discovery of novel 4-(2-fluorophenoxy)quinoline derivatives as c-Met inhibitors using isocyanide-involved multicomponent reactions
Fang, Sen-Biao,Li, Hui-Jing,Li, Qin-Ying,Nan, Xiang,Wu, Yan-Chao
, (2020)
The c-Met kinase has emerged as a promising target for the development of small molecule antitumor agents because of its close relationship with the progression of many human cancers, poor clinical outcomes and even drug resistance. In this study, two novel series of 6,7-disubstitued-4-(2-fluorophenoxy)quinoline derivatives containing α-acyloxycarboxamide or α-acylaminoamide scaffolds were designed, synthesized, and evaluated for their in vitro biological activities against c-Met kinase and four cancer cell lines (H460, HT-29, MKN-45, and MDA-MB-231). Most of the target compounds exhibited moderate to significant potency and possessed selectivity for H460 and HT-29 cancer cell lines. The preliminary structure-activity relationships indicated that α-acyloxycarboxamide or α-acylaminoamide as 5-atom linker contributed to the antitumor potency. Among these compounds, compound 10m (c-Met IC50 = 2.43 nM, a multitarget tyrosine kinase inhibitor) exhibited the most potent inhibitory activities against H460, HT-29 and MDA-MB-231 cell lines with IC50 of 0.14 ± 0.03 μM, 0.20 ± 0.02 μM and 0.42 ± 0.03 μM, which were 1.7-, 1.3- and 1.6-fold more active than foretinib, respectively. In addition, concentration-dependent assay and time-dependent assay indicated compound 10m can inhibit the proliferation of H460 cell in a time and concentration dependent manner. Moreover, docking studies revealed the common mode of interaction with the c-Met binding site, suggesting that 10m is a potential candidate for cancer therapy deserving further study.
Fine chemicals from lignosulfonates. 2. Synthesis of veratric acid from acetovanillon
Bjorsvik, Hans-Rene,Norman, Kristine
, p. 341 - 346 (1999)
An optimisation study based upon experimental data obtained from multivariate statistical experimental design and modelling for the haloform reaction used for synthesis of 3,4-dimethoxybenzoic acid from 3,4-dimethoxy acetophenone is reported. It is shown how the different controllable process variables influence both the yield of 3,4-dimethoxybenzoic acid and the formation of the side product 2-chloro-4,5-dimelhoxybenzoic acid. Two predictive multivariate models are derived and used to predict optimal conditions for the oxidation process. Using these models, a yield of 90% (from approximately 60%) of desired product is achieved. Moreover, the model describing the formation of the side-product can in fact also be applied to optimise a procedure for obtaining 2-chloro-4,5-dimethoxybenzoic acid in substantial quantities. One experiment showed that the side-product could be formed in a quantity of >20%.
The immobilized porphyrin-mediator system Mn(TMePyP)/clay/HBT (clay-PMS): A lignin peroxidase biomimetic catalyst in the oxidation of lignin and lignin model compounds
Crestini, Claudia,Pastorini, Alessandra,Tagliatesta, Pietro
, p. 4477 - 4483 (2004)
A biomimetic system for lignin peroxidase (LiP) was designed by using a cationic porphyrin, [Mn(TMePyP)OAc5], supported on the smectitic clay montmorillonite [Mn(TMe-PyP)/clay]. The natural role of the polypeptidic pocket of LiP was mimicked by the clay. The possibility to use low-molecular-weight redox mediators as active readily diffusible oxidizing species has been investigated. This assembly - a sort of "synthetic enzyme" - can be defined as an immobilized porphyrin-mediator system (clay-PMS). The clay-PMS was found to be a stable, recyclable, and efficient catalyst for the environmentally friendly H2O2-catalyzed oxidation of different lignins and representative lignin model compounds. The clay-PMS showed a higher reactivity than Mn(TMePyP)/clay alone due to an effective role of the redox mediator on the oxidation. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.
Kinetics of oxidation of benzyl alcohols by the dication and radical cation of ABTS. Comparison with laccase-ABTS oxidations: An apparent paradox
Branchi, Barbara,Galli, Carlo,Gentili, Patrizia
, p. 2604 - 2614 (2005)
Laccase, a blue copper oxidase, in view of its moderate redox potential can oxidise only phenolic compounds by electron-transfer. However, in the presence of ABTS (2,2'-azinobis(3-ethylbenzthiazoline-6-sulfonate) as a redox mediator, laccase reacts with the more difficult to oxidise non-phenolic substrates, such as benzyl alcohols. The role of ABTS in these mediated oxidations is investigated. Redox interaction with laccase could produce in situ two reactive intermediates from ABTS, namely ABTS++ or ABTS ?+. These species have been independently generated by oxidation with Ce(IV) or Co(III) salts, respectively, and their efficiency as monoelectronic oxidants tested in a kinetic study towards a series of non-phenolic substrates; a Marcus treatment is provided in the case of ABTS ++. On these grounds, intervention of ABTS++ as a reactive intermediate in laccase-ABTS oxidations appears unlikely, because the experimental conditions under which ABTS++ is unambiguously generated, and survives long enough to serve as a diffusible mediator, are too harsh (2 M H2SO4 solution) and incompatible with the operation of the enzyme. Likewise, ABTS?+ seems an intermediate of limited importance in laccase-ABTS oxidations, because this weaker monoelectronic oxidant is unable to react directly with many of the non-phenolic substrates that laccase-ABTS can oxidise. To solve this paradox, it is alternatively suggested that degradation by-products of either ABTS ++ or ABTS?+ are formed in situ by hydrolysis during the laccase-ABTS reactions, and may be responsible for the observed oxidation of non-phenolics. The Royal Society of Chemistry 2005.
Enhanced activity of nanocrystalline Beta zeolite for acylation of veratrole with acetic anhydride
Al-Turkustani, Aisha Mahmood Abdulkareem,Selvin, Rosilda
, p. 4247 - 4251 (2016)
Friedel-Craft acylation of veratrole using homogeneous acid catalysts such as AlCl3, FeCl3, ZnCl2, and HF etc. produces acetoveratrone, (3′ ,4′-dimethoxyacetophenone), which is the intermediate for synthesis of papavarine alkaloids. The problems associated with these homogeneous catalysts can be overcome by using heterogeneous solid catalysts. Since acetoveratrone is a larger molecule, large pore Beta zeolites with smaller particle sizes are beneficial for the liquid-phase acylation of veratrole, for easy diffusion of reactants and products. The present study aims in the acylation of veratrole with acetic anhydride using nanocrystalline Beta Zeolite catalyst. A systematic investigation of the effects of various reaction parameters was done. The catalysts were characterized for their structural features by using XRD, TEM and DLS analyses. The catalytic activity of nanocrystalline Beta zeolite was compared with commercial Beta zeolite for the acylation and was found that nanocrystalline Beta zeolite possessed superior activity.
Microbial synthesis of (+)-(3R)-ethyl 3-hydroxy-3-(3,4-dimethoxyphenyl)propionate
Bardot, Valerie,Besse, Pascale,Gelas-Miahle, Yvonne,Remuson, Roland,Veschambre, Henri
, p. 1077 - 1088 (1996)
From the microbiological reduction of ethyl 3-oxo-3-(3,4-dimethoxyphenyl)-propionate, (+)-(3R)-ethyl 3-hydroxy-3-(3,4-dimethoxyphenyl)propionate was prepared on a quantitative scale. The absolute configuration was assigned by X-ray structural determination of the crystallized camphanate derivative.
Radiation-induced effects in lignin model compounds: A pulse and steady-state radiolysis study
Chuaqui,Rajagopal,Kovacs,Stepanik,Merritt,Gyorgy,Whitehouse,Ewing
, p. 9689 - 9698 (1993)
A lignin model compound β-(2-methoxyphenoxy)-3,4-dimethoxyacetophenone (1) was subjected to 60Co gamma irradiation and pulse radiolysis under different conditions (dose, medium, pH). interaction with hydroxyl radicals resulted in aryl hydroxylation, fragmentation, and cleavage. A hydroxylation-cleavage pathway was found at all pH values. At alkaline pH, fragmentation reactions were also observed. The predominant reaction with solvated electrons was fragmentation of the β-aryl ether bond followed by cleavage reactions.
The dehydrogenative oxidation of aryl methanols using an oxygen bridged [Cu-O-Se] bimetallic catalyst
Choudhury, Prabhupada,Behera, Pradyota Kumar,Bisoyi, Tanmayee,Sahu, Santosh Kumar,Sahu, Rashmi Ranjan,Prusty, Smruti Ranjita,Stitgen, Abigail,Scanlon, Joseph,Kar, Manoranjan,Rout, Laxmidhar
supporting information, p. 5775 - 5779 (2021/04/12)
Herein, we report a new protocol for the dehydrogenative oxidation of aryl methanols using the cheap and commercially available catalyst CuSeO3·2H2O. Oxygen-bridged [Cu-O-Se] bimetallic catalysts are not only less expensive than other catalysts used for the dehydrogenative oxidation of aryl alcohols, but they are also effective under mild conditions and at low concentrations. The title reaction proceeds with a variety of aromatic and heteroaromatic methanol examples, obtaining the corresponding carbonyls in high yields. This is the first example using an oxygen-bridged copper-based bimetallic catalyst [Cu-O-Se] for dehydrogenative benzylic oxidation. Computational DFT studies reveal simultaneous H-transfer and Cu-O bond breaking, with a transition-state barrier height of 29.3 kcal mol?1
STRONGLY LEWIS ACIDIC METAL-ORGANIC FRAMEWORKS FOR CONTINUOUS FLOW CATALYSIS
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Paragraph 0216-0220; 0239; 0255, (2021/02/26)
Lewis acidic metal-organic framework (MOF) materials comprising triflate-coordinated metal nodes are described. The materials can be used as heterogenous catalysts in a wide range of organic group transformations, including Diels-Alder reactions, epoxide-ring opening reactions, Friedel-Crafts acylation reactions and alkene hydroalkoxylation reactions. The MOFs can also be prepared with metallated organic bridging ligands to provide heterogenous catalysts for tandem reactions and/or prepared as composites with support particles for use in columns of continuous flow reactor systems. Methods of preparing and using the MOF materials and their composites are also described.
