- Structural understanding of 5-(4-hydroxy-phenyl)-N-(2-(5-methoxy-1H-indol-3-yl)-ethyl)-3-oxopentanamide as a neuroprotectant for Alzheimer's disease
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In our continuing efforts to develop novel neuroprotectants for Alzheimer's disease (AD), a series of analogs based on a lead compound that was recently shown to target the mitochondrial complex I were designed, synthesized and biologically characterized to understand the structure features that are important for neuroprotective activities. The results from a cellular AD model highlighted the important roles of the 4-OH on the phenyl ring and the 5-OCH3 on the indole ring of the lead compound. The results also demonstrated that the β-keto moiety can be modified to retain or improve the neuroprotective activity. Docking studies of selected analogs to the FMN site of mitochondrial complex I also supported the observed neuroprotective activities. Collectively, the results provide further information to guide optimization and development of analogs based on this chemical scaffold as neuroprotectants with a novel mechanism of action for AD.
- Green, Jakob,Jiang, Yuqi,Kellogg, Glen E.,Saathoff, John,Xu, Yiming,Zhang, Shijun
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- Short Total Synthesis of (±)-Gelliusine e and 2,3′-Bis(indolyl)ethylamines via PTSA-Catalyzed Transindolylation
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A first and short total synthesis of the marine sponge 2,3′-bis(indolyl)ethylamine (2,3′-BIEA) alkaloid (±)-gelliusine E was performed in both a three-step divergent approach and a one-pot three-component approach with an overall yield of up to 58%. A key feature of the novel strategy is PTSA-catalyzed transindolylation of the readily synthesized 3,3′-BIEAs with tryptamine derivatives. The structure of the isolated natural product is revised as protonated (±)-gelliusine E (4′). By design, this modular route allows the rapid synthesis of other members of the 2,3′-BIEA family, for example, (±)-6,6′-bis-(debromo)-gelliusine F and analogues with step economy, operational simplicity, and reduced waste. Furthermore, their cytotoxicity in breast cancer cells was investigated.
- Chantana, Chayamon,Iawsipo, Panata,Jaratjaroonphong, Jaray,Sirion, Uthaiwan
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p. 13360 - 13370
(2021/10/01)
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- The discovery of tetrahydro-β-carbolines as inhibitors of the kinesin Eg5
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A series of tetrahydro-β-carbolines were identified by HTS as inhibitors of the kinesin Eg5. Molecular modeling and medicinal chemistry techniques were employed to explore the SAR for this series with a focus of removing potential metabolic liabilities and improving cellular potency.
- Barsanti, Paul A.,Wang, Weibo,Ni, Zhi-Jie,Duhl, David,Brammeier, Nathan,Martin, Eric,Bussiere, Dirksen,Walter, Annette O.
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scheme or table
p. 157 - 160
(2010/04/02)
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- THIOPHENE-TRYPTAMINE DERIVATIVES
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5-Thiophene-substituted tryptamine analogs are provided, which exhibit selectivity towards 5-HT D1 receptors and consequently show potential in alleviation of the symptoms of migraine. The analogs are represented by the following general chemical formula:
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- 5-HT(1D) receptor agonist properties of novel 2-[5- [[(trifluoromethyl)sulfonyl]oxy]indolyl]ethylamines and their use as synthetic intermediates
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2-[5-[[(Trifluoromethyl)sulfonyl]oxy]-1H-indol-3-yl]ethylamine (18), its N,N'-di-n-propyl (12), N,N-diethyl (13), and N,N-dimethyl (14) derivatives, and 4-[3-[2-(N,N-dimethylamino)ethyl]-1H-indol-3-yl]-N-(p- methoxybenzyl)acrylamide (GR46611, 19) were syn
- Barf,De Boer,Wikstrom,Peroutka,Svensson,Ennis,Ghazal,McGuire,Smith
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p. 4717 - 4726
(2007/10/03)
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