- A Hg(OTf)2-Catalyzed Enolate Umpolung Reaction Enables the Synthesis of Coumaran-3-ones and Indolin-3-ones
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The potential of mercury catalysis has been extended to the arena of enolate umpolung reactions for the first time by the generation of enolonium species via Hg(OTf)2-catalyzed N-oxide addition to alkynes. The enolonium species formed can undergo intramolecular nucleophilic attack by hydroxyl or amino groups, leading to the synthesis of various coumaran-3-ones and indolin-3-ones.
- Dai, Ning,Hu, Weican,Qian, Guoying,Rong, Zhouting
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p. 3286 - 3290
(2020/04/21)
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- Catalytic synthesis method of 3-benzofuranone compound
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The invention discloses a catalytic synthesis method of a 3-benzofuranone compound. The catalytic synthesis method comprises the following steps: dissolving a 2-acetenyl phenol derivative into a solvent dichloromethane at normal temperature and normal pressure according to a molar volume ratio of the 2-acetenyl phenol derivative to the dichloromethane of 1:5mmol/mL, so as to obtain a dichloromethane solution of the 2-acetenyl phenol derivative; then adding mercury trifluoromethanesulfonate and pyridine-N-oxide into a dichloromethane solution of the 2-ethynylphenol derivative, wherein the molaramounts of mercury trifluoromethanesulfonate and pyridine-N-oxide are respectively 5% and 120% of the molar amount of the 2-ethynylphenol derivative; and then performing stirring for 1 hour at room temperature, and performing reacting to generate the 3-benzofuranone compound. The market price of the catalyst mercury trifluoromethanesulfonate used in the catalytic synthesis method is lower than 30yuan/g, the cost is low, the operation is simple, the reaction time is short, the reaction conditions are mild, the reaction yield is high, and the yield can reach 91.0-96.0%.
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Paragraph 0022; 0023
(2020/05/14)
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- Virtual screening-driven discovery of dual 5-HT6/5-HT2A receptor ligands with pro-cognitive properties
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A virtual screening campaign aimed at finding structurally new compounds active at 5-HT6R provided a set of candidates. Among those, one structure, 4-(5-{[(2-{5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl}ethyl)amino]methyl}furan-2-yl)phenol (1, 5-HT6R Ki = 91 nM), was selected as a hit for further optimization. As expected, the chemical scaffold of selected compound was significantly different from all the serotonin receptor ligands published to date. Synthetic efforts, supported by molecular modelling, provided 43 compounds representing different substitution patterns. The derivative 42, 4-(5-{[(2-{5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl}ethyl)amino]methyl}furan-2-yl)phenol (5-HT6R Ki = 25, 5-HT2AR Ki = 32 nM), was selected as a lead and showed a good brain/plasma concentration profile, and it reversed phencyclidine-induced memory impairment. Considering the unique activity profile, the obtained series might be a good starting point for the development of a novel antipsychotic or antidepressant with pro-cognitive properties.
- Staroń, Jakub,Kurczab, Rafa?,Warszycki, Dawid,Sata?a, Grzegorz,Krawczyk, Martyna,Bugno, Ryszard,Lenda, Tomasz,Popik, Piotr,Hogendorf, Adam S.,Hogendorf, Agata,Dubiel, Krzysztof,Mat?oka, Miko?aj,Moszczyński-P?tkowski, Rafa?,Pieczykolan, Jerzy,Wieczorek, Maciej,Zajdel, Pawe?,Bojarski, Andrzej J.
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supporting information
(2019/11/28)
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- Discovery of benzofuran-3(2H)-one derivatives as novel DRAK2 inhibitors that protect islet β-cells from apoptosis
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Death-associated protein kinase-related apoptosis-inducing kinase-2 (DRAK2) is a serine/threonine kinase that plays a key role in a wide variety of cell death signaling pathways. Inhibition of DRAK2 was found to efficiently protect islet β-cells from apoptosis and hence DRAK2 inhibitors represent a promising therapeutic strategy for the treatment of diabetes. Only very few chemical entities targeting DRAK2 are currently known. We carried out a high throughput screening and identified compound 4 as a moderate DRAK2 inhibitor with an IC50value of 3.15?μM. Subsequent SAR studies of hit compound 4 led to the development of novel benzofuran-3(2H)-one series of DRAK2 inhibitors with improved potency and favorable selectivity profiles against 26 selected kinases. Importantly, most potent compounds 40 (IC50?=?0.33?μM) and 41 (IC50?=?0.25?μM) were found to protect islet β-cells from apoptosis in dose-dependent manners. These data support the notion that small molecule inhibitors of DRAK2 represents a promising strategy for the treatment of diabetes.
- Wang, Sheng,Xu, Lei,Lu, Yu-Ting,Liu, Yu-Fei,Han, Bing,Liu, Ting,Tang, Jie,Li, Jia,Wu, Jiangping,Li, Jing-Ya,Yu, Li-Fang,Yang, Fan
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p. 195 - 208
(2017/03/02)
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- Practical, modular, and general synthesis of 3-coumaranones through gold-catalyzed intermolecular alkyne oxidation strategy
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A gold-catalyzed intermolecular alkyne oxidation for the preparation of 3-coumaranones has been developed. Using 8-isopropylquinoline N-oxides as oxidants, the reactions of o-ethynylanisoles afford versatile 3-coumaranones in moderate to good isolated yields. The synthetic utility of this chemistry is also indicated by the synthesis of the natural product sulfuretin.
- Shu, Chao,Liu, Rongfu,Liu, Shuang,Li, Jian-Qiao,Yu, Yong-Fei,He, Qiao,Lu, Xin,Ye, Long-Wu
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supporting information
p. 91 - 95
(2015/02/19)
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- Novel benzofuran derivatives with dual 5-HT1A receptor and serotonin transporter affinity
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Several benzofuran derivatives linked to a 3-indoletetrahydropyridine through an alkyl chain were prepared and evaluated for serotonin transporter and 5-HT1A receptor affinities. Their design, synthesis and structure-activity relationships are described.
- Venkatesan, Aranapakam M.,Dos Santos,Ellingboe, John,Evrard, Deborah A.,Harrison, Boyd L.,Smith, Deborah L.,Scerni, Rosemary,Hornby, Geoffrey A.,Schechter, Lee E.,Andree, Terrence H.
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scheme or table
p. 824 - 827
(2010/06/13)
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- BENZOFURANYL- AND BENZOTHIENYL- PIPERAZINYL QUINOLINES AND METHODS OF THEIR USE
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Benzofuranyl- and benzothienyl-piperzinyl quinoline derivatives and compositions containing such compounds are disclosed. Methods of using benzofuranyl- and benzothienyl-piperzinyl quinoline derivatives and compositions containing such composition in the treatment and/or prevention of serotonin-related disorders, such as depression and anxiety, are also disclosed. In addition, processes for the preparation of benzofuranyl- and benzothienyl-piperzinyl quinoline derivatives are disclosed.
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Page/Page column 25
(2009/04/24)
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- Piperazine-piperidine antagonists and agonists of the 5-HT1A receptor
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The present invention relates to novel piperazine-piperidine compounds. The compounds are useful as 5-HT1A binding agents, particularly as 5-HT1A receptor antagonists and agonists. These compounds are useful in treating central nervous system disorders, such as cognition disorders, anxiety disorders, depression and sexual dysfunction.
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Page/Page column 48
(2010/11/25)
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- Structure-based design leads to the identification of lithium mimetics that block mania-like effects in rodents. Possible new GSK-3β therapies for bipolar disorders
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More than two million American adults, or approximately one percent of the population 18 years or older, suffer from bipolar disorder. Current treatments include the so-called "mood stabilizers," lithium and valproic acid. Both are relatively dated drugs that are only partially effective and produce various undesirable side effects including weight gain. Based upon continued efforts to understand the molecular target for lithium, it now appears that specific inhibitors of the enzyme glycogen synthase kinase-3β (GSK-3β) may mimic the therapeutic action of mood stabilizers and might therefore allow for the design of improved drugs for treating patients with bipolar disorder as well as certain neurodegenerative disorders. Furthermore, the pro-apoptotic properties of the GSK-3 enzyme suggest the possible use of such inhibitors as neuroprotective agents. In fact, neuroprotection may contribute to the treatment of mood disorders. The present chemistry, modeling, and biology efforts have identified 3-benzofuranyl-4-indolylmaleimides as potent and relatively selective GSK-3β inhibitors. The best ligand in this series (having a Ki value of 4.6 nM against GSK-3β) was studied in a novel mouse model of mania that has recently been validated with several clinically effective mood stabilizers. This study presents the first demonstration of the efficacy of a GSK-3β inhibitor in this mouse model of mania. Selective brain penetrable GSK-3 ligands like those described herein become valuable research tools in better defining the role of this multifaceted kinase in both physiological and pathophysiological events.
- Kozikowski, Alan P.,Gaisina, Irina N.,Yuan, Hongbin,Petukhov, Pavel A.,Blond, Sylvie Y.,Fedolak, Allison,Caldarone, Barbara,McGonigle, Paul
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p. 8328 - 8332
(2008/02/09)
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- Piperidinyl indole and tetrohydropyridinyl indole derivatives and method of their use
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3-Piperidin-4-yl-1H-indole and 3-(1,2,3,6-tetrahydro-pyridin-4-yl)-1H-indole derivatives are disclosed. Methods of using the derivatives and compositions containing the derivatives in the prevention and/or treatment of serotonin disorders, such as depression and anxiety, are also disclosed. Additionally, processes for the preparation of 3-piperidin-4-yl-1H-indole and 3-(1,2,3,6-tetrahydro-pyridin-4-yl)-1H-indole derivatives are disclosed.
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Page/Page column 15
(2010/02/10)
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- BENZOFURANYL-AND BENZOTHIENYL-PIPERAZINYL QUINOLINES AND METHODS OF THEIR USE
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Benzofuranyl-and benzothienyl-piperzinyl quinoline derivatives and compositions containing such compounds are disclosed. Methods of using benzofuranyl- and benzothienyl-piperzinyl quinoline derivatives and compositions containing such composition in the treatment and/or prevention of serotonin-related disorders, such as depression and anxiety, are also disclosed. In addition, processes for the preparation of benzofuranyl- and benzothienyl-piperzinyl quinoline derivatives are disclosed.
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