93033-60-4Relevant academic research and scientific papers
HCl-mediated cascade cyclocondensation of oxygenated arylacetic acids with arylaldehydes: one-pot synthesis of 1-arylisoquinolines
Hsueh, Nai-Chen,Chen, Shin-Mei,Lin, Chun-Yi,Chang, Meng-Yang
, p. 1047 - 1059 (2021/02/16)
In this paper, a concise, open-vessel synthesis of 1-arylisoquinolines is describedviaHCl-mediated intermolecular cyclocondensation of oxygenated arylacetic acids with arylaldehydes in the presence of NH2OH and alcoholic solvents under mild and one-pot reaction conditions. A plausible mechanism is proposed and discussed herein. In the overall reaction process, only water was generated as the byproduct. Various environmentally friendly reaction conditions are investigated for convenient transformationviathe (4C + 1C + 1N) annulation. This protocol provides a highly effective ring closureviathe formations of one carbon-carbon (C-C) bond, two carbon-nitrogen (C-N) bonds and one carbon-oxygen (C-O) bond.
Identification of histone deacetylase inhibitors with (arylidene)aminoxy scaffold active in uveal melanoma cell lines
Nencetti, Susanna,Cuffaro, Doretta,Nuti, Elisa,Ciccone, Lidia,Rossello, Armando,Fabbi, Marina,Ballante, Flavio,Ortore, Gabriella,Carbotti, Grazia,Campelli, Francesco,Banti, Irene,Gangemi, Rosaria,Marshall, Garland R.,Orlandini, Elisabetta
, p. 34 - 47 (2020/11/04)
Uveal melanoma (UM) represents an aggressive type of cancer and currently, there is no effective treatment for this metastatic disease. In the last years, histone deacetylase inhibitors (HDACIs) have been studied as a possible therapeutic treatment for UM, alone or in association with other chemotherapeutic agents. Here we synthesised a series of new HDACIs based on the SAHA scaffold bearing an (arylidene)aminoxy moiety. Their HDAC inhibitory activity was evaluated on isolated human HDAC1, 3, 6, and 8 by fluorometric assay and their binding mode in the catalytic site of HDACs was studied by molecular docking. The most promising hit was the quinoline derivative VS13, a nanomolar inhibitor of HDAC6, which exhibited a good antiproliferative effect on UM cell lines at micromolar concentration and a capability to modify the mRNA levels of HDAC target genes similar to that of SAHA.
A Transition-Metal-Free One-Pot Cascade Process for Transformation of Primary Alcohols (RCH2OH) to Nitriles (RCN) Mediated by SO2F2
Jiang, Ying,Sun, Bing,Fang, Wan-Yin,Qin, Hua-Li
supporting information, p. 3190 - 3194 (2019/05/21)
A new transition-metal-free one-pot cascade process for the direct conversion of alcohols to nitriles was developed without introducing an “additional carbon atom”. This protocol allows transformations of readily available, inexpensive, and abundant alcohols to highly valuable nitriles.
SO 2 F 2 -Promoted Dehydration of Aldoximes: A Rapid and Simple Access to Nitriles
Ding, Chengrong,Mei, Guangyao,Wang, Haibo,Zhang, Guofu,Zhao, Yiyong
supporting information, p. 1484 - 1488 (2019/07/15)
A rapid, simple and mild process for the dehydration of aldoximes to give the corresponding nitriles, which utilizes SO 2 F 2 as an efficient reagent, has been developed. A variety of (hetero)arene, alkene, alkyne and aliphatic aldoximes proceeded with high efficiency to afford nitriles in excellent to quantitative yields with great functional group compatibilities in acetonitrile under ambient conditions. Furthermore, an eco-friendly synthetic protocol to access nitriles from aldehydes with ortho -, meta - and para -nitrile groups was also described in aqueous methanol by using inorganic base Na 2 CO 3, and a one-pot synthetic strategy to generate nitriles from aldehydes was proved to be feasible.
Differentiating Antiproliferative and Chemopreventive Modes of Activity for Electron-Deficient Aryl Isothiocyanates against Human MCF-7 Cells
Anderson, Ruthellen H.,Lensing, Cody J.,Forred, Benjamin J.,Amolins, Michael W.,Aegerter, Cassandra L.,Vitiello, Peter F.,Mays, Jared R.
, p. 1695 - 1710 (2018/08/01)
The consumption of Brassica vegetables provides beneficial effects through organic isothiocyanates (ITCs), products of the enzymatic hydrolysis of glucosinolate secondary metabolites. The ITC l-sulforaphane (l-SFN) is the principle agent in broccoli that demonstrates several modes of anticancer action. While the anticancer properties of ITCs like l-SFN have been extensively studied and l-SFN has been the subject of multiple human clinical trials, the scope of this work has largely been limited to those derivatives found in nature. Previous studies have demonstrated that structural changes in an ITC can lead to marked differences in a compound's potency to 1) inhibit the growth of cancer cells, and 2) alter cellular transcriptional profiles. This study describes the preparation of a library of non-natural aryl ITCs and the development of a bifurcated screening approach to evaluate the dose- and time-dependence on antiproliferative and chemopreventive properties against human MCF-7 breast cancer cells. Antiproliferative effects were evaluated using a commercial MTS cell viability assay. Chemopreventive properties were evaluated using an antioxidant response element (ARE)-promoted luciferase reporter assay. The results of this study have led to the identification of 1) several key structure–activity relationships and 2) lead ITCs for continued development.
Glucose-derived spiro-isoxazolines are anti-hyperglycemic agents against type 2 diabetes through glycogen phosphorylase inhibition
Goyard, David,Kónya, Bálint,Chajistamatiou, Aikaterini S.,Chrysina, Evangelia D.,Leroy, Jérémy,Balzarin, Sophie,Tournier, Michel,Tousch, Didier,Petit, Pierre,Duret, Cédric,Maurel, Patrick,Somsák, László,Docsa, Tibor,Gergely, Pál,Praly, Jean-Pierre,Azay-Milhau, Jacqueline,Vidal, Sébastien
supporting information, p. 444 - 454 (2015/12/24)
Glycogen phosphorylase (GP) is a target for the treatment of hyperglycaemia in the context of type 2 diabetes. This enzyme is responsible for the depolymerization of glycogen into glucose thereby affecting the levels of glucose in the blood stream. Twelve
Synthesis of Novel 3-aryl-1-oxa-2,8-diazaspiro[4.5]dec-2-ene Derivatives and Their Biological Evaluation Against Protein Tyrosine Phosphatase 1B
Wang, Wen-Long,Chen, Xia,Gao, Li-Xin,Sheng, Li,Li, Jing-Ya,Li, Jia,Feng, Bainian
, p. 1161 - 1167 (2015/10/28)
A series of novel 3-aryl-1-oxa-2,8-diazaspiro[4.5]dec-2-ene derivatives were designed, synthesized, and evaluated as a new class of inhibitors against protein tyrosine phosphatase 1B. Among them, compound 6f displayed moderate inhibitory activity with IC50 of 2.87 ± 0.24 μm and can be used as a novel lead compound for the design of inhibitors of protein tyrosine phosphatase 1B. A series of novel 3-aryl-1-oxa-2,8-diazaspiro[4.5]dec-2-ene derivatives were designed, synthesized, and evaluated as a new class of inhibitors against PTP1B. Among them, compound 6f displayed moderate inhibitory activity with IC50 of 2.87 ± 0.24 μm and can be used as a novel lead compound for the design of inhibitors of PTP1B.
Ruthenium-catalyzed rearrangement of aldoximes to primary amides in water
Garcia-Alvarez, Rocio,Diaz-Alvarez, Alba E.,Borge, Javier,Crochet, Pascale,Cadierno, Victorio
, p. 6482 - 6490 (2012/10/30)
The rearrangement of aldoximes to primary amides has been studied using the readily available arene-ruthenium(II) complex [RuCl2(η 6-C6Me6){P(NMe2)3}] (5 mol %) as catalyst. Reactions proceeded cleanly in pure water at 100 °C without the assistance of any cocatalyst, affording the desired amides in high yields (70-90%) after short reaction times (1-7 h). The process was operative with both aromatic, heteroaromatic, α,β-unsaturated, and aliphatic aldoximes and tolerated several functional groups. Reaction profiles and experiments using 18O-labeled water indicate that two different mechanisms are implicated in these transformations. In both of them, nitrile intermediates are initially formed by dehydration of the aldoximes. These intermediates are then hydrated to the corresponding amides by the action of a second molecule of aldoxime or water. A kinetic analysis of the rearrangement of benzaldoxime to benzamide is also discussed.
Synthesis of heteroaromatic analogues of (2-aryl-1-cyclopentenyl-1-alkylidene)-(arylmethyloxy)amine COX-2 inhibitors: Effects on the inhibitory activity of the replacement of the cyclopentene central core with pyrazole, thiophene or isoxazole ring
Balsamo, Aldo,Coletta, Isabella,Guglielmotti, Angelo,Landolfi, Carla,Mancini, Francesca,Martinelli, Adriano,Milanese, Claudio,Minutolo, Filippo,Nencetti, Susanna,Orlandini, Elisabetta,Pinza, Mario,Rapposelli, Simona,Rossello, Armando
, p. 157 - 168 (2007/10/03)
Several heteroaromatic analogues of (2-aryl-1-cyclopentenyl-1-alkylidene)-(arylmethyloxy)amine COX-2 inhibitors, in which the cyclopentene moiety was replaced by pyrazole, thiophene or isoxazole ring, were synthesized, in order to verify the influence of the different nature of the central core on the COX inhibitory properties of these kinds of molecules. Among the compounds tested, only the 3-(p-methylsulfonylphenyl) substituted thiophene derivatives 17 and 22, showed a certain COX-2 inhibitory activity, accompanied by an appreciable COX-2 versus COX-1 selectivity. Only one of the 1-(p-methylsulfonylphenyl)pyrazole compounds (16) displayed a modest inhibitory activity towards both type of isoenzymes, while the pyrazole 1-(p-aminosulfonylphenyl) substituted 12 proved to be significantly active only towards COX-1. All the isoxazole derivatives were inactive on both COX isoforms.
Inactivation of mitochondrial monoamine oxidase B by methylthio-substituted benzylamines
Lu, Xingliang,Rodriguez, Maria,Gu, Wenxin,Silverman, Richard B.
, p. 4423 - 4430 (2007/10/03)
Mitochondrial monoamine oxidase was inactivated by o-mercaptobenzylamine (1) and o- (2) and p-methylthiobenzylamine (5). Experiments were carried out to provide evidence for possible mechanisms of inactivation. The corresponding o- (3) and p-hydroxybenzylamine (4) are not inactivators. Four radiolabeled analogues of 2 and 5, having radioactivity at either the methyl or benzyl groups, were synthesized, and all were shown to incorporate multiple equivalents of radioactivity into the enzyme. Inactivation in the presence of an electrophile scavenger decreased the number of molecules incorporated, but still multiple molecules became incorporated; catalase did not further reduce the number of inactivator molecules bound. Two inactivation mechanisms are proposed, one involving a nucleophilic aromatic substitution (SNAr) mechanism and the other a dealkylation mechanism. Evidence for both mechanisms is that inactivation leads to reduction of the flavin (oxidation of the inactivator), but upon denaturation the flavin is reoxidized, indicating that attachment is not at the flavin. A cysteine titration indicates the loss of four cysteines after inactivation and denaturation. Support for the S NAr mechanism was obtained by showing that o- and p-chlorobenzylamine also inactivate MAO. Chemical model studies were carried out that also support both SNAr and dealkylation mechanisms.
