28615-67-0Relevant articles and documents
Metal- and Acid-Free C-H Formylation of Nitrogen Heterocycles: Using Trioxane as an Aldehyde Equivalent Enabled by an Organic-Soluble Oxidant
Ganley, Jacob M.,Christensen, Melodie,Lam, Yu-Hong,Peng, Zhengwei,Angeles, Angie R.,Yeung, Charles S.
, p. 5752 - 5756 (2018)
A metal-free, innate, and practical C-H formylation of nitrogen heterocycles using trioxane as a formyl equivalent is reported. This reaction provides a mild and robust method for modifying medicinally relevant heterocycles with an aldehyde handle. The use of an organic soluble oxidant, tetrabutylammonium persulfate, is critical in promoting the desired coupling.
From dual binding site acetylcholinesterase inhibitors to allosteric modulators: A new avenue for disease-modifying drugs in Alzheimer's disease
Chierrito, Talita P.C.,Mantoani, Susimaire P.,Roca, Carlos,Requena, Carlos,Sebastian-Perez, Victor,Castillo, Willian O.,Moreira, Natalia C.S.,Pérez, Concepción,Sakamoto-Hojo, Elza T.,Takahashi, Catarina S.,Jiménez-Barbero, Jesús,Ca?ada, F. Javier,Campillo, Nuria E.,Martinez, Ana,Carvalho, Ivone
, p. 773 - 791 (2017)
The lack of an effective treatment for Alzheimer’ disease (AD), an increasing prevalence and severe neurodegenerative pathology, boost medicinal chemists to look for new drugs. Currently, only acethylcholinesterase (AChE) inhibitors and glutamate antagonist have been approved to the palliative treatment of AD. Although they have a short-term symptomatic benefits, their clinical use have revealed important non-cholinergic functions for AChE such its chaperone role in beta-amyloid toxicity. We propose here the design, synthesis and evaluation of non-toxic dual binding site AChEIs by hybridization of indanone and quinoline heterocyclic scaffolds. Unexpectely, we have found a potent allosteric modulator of AChE able to target cholinergic and non-cholinergic functions by fixing a specific AChE conformation, confirmed by STD-NMR and molecular modeling studies. Furthermore the promising biological data obtained on human neuroblastoma SH-SY5Y cell assays for the new allosteric hybrid 14, led us to propose it as a valuable pharmacological tool for the study of non-cholinergic functions of AChE, and as a new important lead for novel disease modifying agents against AD.
Discovery of 4-anilinoquinolinylchalcone derivatives as potential NRF2 activators
Chen, Yeh-Long,Chen, Yi-Siao,Kao, Yu-Tse,Lee, Jin-Ching,Tang, Kai-Wei,Tseng, Chih-Hua,Tzeng, Cherng-Chyi,Yen, Chia-Hung
, (2020)
Activation of nuclear factor erythroid-2-related factor 2 (NRF2) has been proven to be an effective means to prevent the development of cancer, and natural curcumin stands out as a potent NRF2 activator and cancer chemopreventive agent. In this study, we have synthesized a series of 4-anilinoquinolinylchalcone derivatives, and used a NRF2 promoter-driven firefly luciferase reporter stable cell line, the HaCaT/ARE cells, to screen a panel of these compounds. Among them, (E)-3-{4-[(4-acetylphenyl)amino]quinolin-2-yl}-1-(4-fluorophenyl)prop-2-en-1-one (13b) significantly increased NRF2 activity in the HaCaT cell with a half maximal effective concentration (EC50) value of 1.95 μM. Treatment of compound 13b upregulated HaCaT cell NRF2 expression at the protein level. Moreover, the mRNA level of NRF2 target genes, heme oxygenase-1 (HO-1), glutamate-cysteine ligase catalytic subunit (GCLC), and glucose-6-phosphate dehydrogenase (G6PD) were significantly increased in HaCaT cells upon the compound 13b treatment. The molecular docking results exhibited that the small molecule 13b is well accommodated by the bound region of Kelch-like ECH-associated protein 1 (Keap1)-Kelch and NRF2 through stable hydrogen bonds and hydrophobic interaction, which contributed to the enhancement of affinity and stability between the ligand and receptor. Compound 13b has been identified as the lead compound for further structural optimization.
Methanol as a formylating agent in nitrogen heterocycles
Xu, Zhengbao,Zhang, Lizhi
, p. 9476 - 9482 (2021/11/17)
A radical mediated C-H direct formylation of N-heteroarenes with methanol is reported. The reaction features a novel iron-catalyzed Minisci oxidative coupling process using commercially available methanol as a formylating reagent. It effectively solved the long-standing problems associated with using methanol as a formylating reagent in these types of reactions. Compared to the traditional Minisci C-H formylation methods, this protocol is highly atom-economical, simple to operate, and environmentally friendly and shows good functional group tolerance. This Minisci formylation strategy is a straightforward approach for the late-stage functionalization of N-heteroarenes. This journal is
Photoredox-Catalyzed Redox-Neutral Minisci C?H Formylation of N-Heteroarenes
Dong, Jianyang,Wang, Xiaochen,Song, Hongjian,Liu, Yuxiu,Wang, Qingmin
supporting information, p. 2155 - 2159 (2020/02/11)
We report a protocol for redox-neutral Minisci C?H formylation of N-heteroarenes using 1,3-dioxoisoindolin-2-yl 2,2-diethoxyacetate as a formyl equivalent at room temperature. This scalable benchtop protocol offers a distinct advantage over traditional reductive carbonylation and Minisci C?H formylation methods in not requiring the use of carbon monoxide, pressurized gas, a stoichiometric reductant, or a stoichiometric oxidant. (Figure presented.).
Endeavors towards transformation of M. tuberculosis thymidylate kinase (MtbTMPK) inhibitors into potential antimycobacterial agents
Jian, Yanlin,Merceron, Romain,De Munck, Steven,Forbes, He Eun,Hulpia, Fabian,Risseeuw, Martijn D.P.,Van Hecke, Kristof,Savvides, Savvas N.,Munier-Lehmann, Hélène,Boshoff, Helena.I.M.,Van Calenbergh, Serge
, (2020/08/19)
As the last enzyme in nucleotide synthesis as precursors for DNA replication, thymidylate kinase of M. tuberculosis (MtbTMPK) attracts significant interest as a target in the discovery of new anti-tuberculosis agents. Earlier, we discovered potent MtbTMPK inhibitors, but these generally suffered from poor antimycobacterial activity, which we hypothesize is due to poor bacterial uptake. To address this, we herein describe our efforts to equip previously reported MtbTMPK inhibitors with targeting moieties to increase the whole cell activity of the hybrid analogues. Introduction of a simplified Fe-chelating siderophore motif gave rise to analogue 17 that combined favorable enzyme inhibitory activity with significant activity against M. tuberculosis (MIC of 12.5 μM). Conjugation of MtbTMPK inhibitors with an imidazo[1,2-a]pyridine or 3,5-dinitrobenzamide scaffold afforded analogues 26, 27 and 28, with moderate MtbTMPK enzyme inhibitory potency, but sub-micromolar activity against mycobacteria without significant cytotoxicity. These results indicate that conjugation with structural motifs known to favor mycobacterial uptake may be a valid approach for discovering new antimycobacterial agents.
Photoredox-Catalyzed Decarboxylative C-H Acylation of Heteroarenes
Jia, Wei,Jian, Yong,Huang, Binbin,Yang, Chao,Xia, Wujiong
supporting information, p. 1881 - 1886 (2018/08/28)
A mild, environmentally friendly, and regioselective acylation of heterocycles with inexpensive carboxylic acids is reported via photoredox catalysis. The strategy is highlighted with good functional group tolerance and substrate scope which could rapidly
Copper-Catalyzed Aerobic Oxidation of Azinylmethanes for Access to Trifluoromethylazinylols
Zheng, Gang,Liu, Hao,Wang, Mang
supporting information, p. 519 - 523 (2016/06/01)
A copper-catalyzed oxygenation of methylazaarenes was found to occur in the absence of both ligand and additive, and has been successfully employed for the synthesis of trifluoromethylazinylketols. This synthetic strategy incorporates aerobic oxidation and a trifluoromethylation in one-pot and provides a novel method for the trifluoromethylation of aliphatic C-H bond.
Novel lipopeptides as antibacterial agents
-
, (2008/06/13)
The present invention relates to novel lipopeptide compounds. The invention also relates to pharmaceutical compositions of these compounds and methods of using these compounds as antibacterial compounds. The invention also relates to methods of producing
Synthesis of 4-[4-(N,N-dimethylsulfamoyl)piperazin-1-yl]-quinolines derivatives as sorbitol dehydrogenase potential inhibitors
Varlet, Didier,Fourmaintraux, Eric,Depreux, Patrick,Lesieur, Daniel
, p. 385 - 396 (2007/10/03)
Synthesis of various quinolines, substituted in position 4 by [4-(N,N-dimethylsulfamoyl)piperazin-1-yl] group and in position 2 by different groups such as hydrogen, methyl, hydroxymethyl, formyl or carboxyl is described. Besides, we have synthesized derivatives of 8-hydroxyquinoline.
