- Diversity-Oriented Synthesis of Coumarin-Linked Benzimidazoles via a One-Pot, Three-Step, Intramolecular Knoevenagel Cyclization
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Diversity-oriented synthesis of coumarin-linked benzimidazoles from N-(2-aminophenyl)-2-cyanoacetamide was achieved via a one-pot, three-step sequential reaction in excellent yields. In situ intramolecular cyclization of the cyanoacetamide afforded benzimidazoles which subsequently underwent a Knoevenagel condensation of the 2-cyanomethylbenzimidazoles with salicylaldehydes promoted by triethylamine to reach the target compounds. An important intermediate, 2-(2-imino-2H-chromen-3-yl)-1H-benzimidazole was characterized by X-ray analysis and further hydrolyzed to 2-(coumarin-3-yl)benzimidazole in acidic condition. Among the synthesized compounds, some were found to be promising inhibitors of porcine kidney d-amino acid oxidase (pkDAO).
- Yao, Po-Hsin Eric,Kumar, Sunil,Liu, Yu-Li,Fang, Chiu-Ping,Liu, Chia-Chen,Sun, Chung-Ming
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supporting information
p. 271 - 275
(2017/04/21)
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- A Novel Mechanistic Study on Ultrasound-Assisted, One-Pot Synthesis of Functionalized Benzimidazo[2,1-b]quinazolin-1(1H)-ones
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Ultrasound-assisted synthesis of benzimidazo[2,1-b]quinazolin-1(1H)-ones was achieved via piperidine-catalyzed three-component reaction of 2-aminobenzimidazoles, an aromatic aldehyde, and 1,3-dione in aqueous isopropanol. This mechanism was first suspected following our identification of unusual reaction intermediates in a one-pot reaction. An unprecedented coupling reaction, it involved a nucleophilic attack by 2-aminobenzimidazole on in situ generated Michael adduct, followed by electrocyclic ring formation reaction. In contrast to the commonly accepted mechanism, that the direct reaction of 2-amino benzimidazole with a Knoevenagel adduct cannot deliver target compounds.
- Chen, Li-Hsun,Chung, Tsai-Wen,Narhe, Bharat D.,Sun, Chung-Ming
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p. 162 - 169
(2016/03/25)
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- Novel Ferroptosis Inhibitors with Improved Potency and ADME Properties
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Ferroptosis is a nonapoptotic, iron-catalyzed form of regulated necrosis that is critically dependent on glutathione peroxidase 4 (GPX4). It has been shown to contribute to liver and kidney ischemia reperfusion injury in mice. A chemical inhibitor discovered by high-throughput screening displayed inhibition of ferroptosis with nanomolar activity and was dubbed ferrostatin-1 (fer-1). Ferrostatins inhibit oxidative lipid damage, but suffer from inherent stability problems due to the presence of an ester moiety. This limits the application of these molecules in vivo, due to rapid hydrolysis of the ester into the inactive carboxylic acid. Previous studies highlighted the importance of the ethyl ester and suggested steric modifications of the ester for generating improved molecules. In this study, we report the synthesis of novel ferroptosis inhibitors containing amide and sulfonamide moieties with improved stability, single digit nanomolar antiferroptotic activity, and good ADME properties suitable for application in in vivo disease models.
- Hofmans, Sam,Berghe, Tom Vanden,Devisscher, Lars,Hassannia, Behrouz,Lyssens, Sophie,Joossens, Jurgen,Van Der Veken, Pieter,Vandenabeele, Peter,Augustyns, Koen
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p. 2041 - 2053
(2016/03/22)
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- Ferrostatins inhibit oxidative lipid damage and cell death in diverse disease models
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Ferrostatin-1 (Fer-1) inhibits ferroptosis, a form of regulated, oxidative, nonapoptotic cell death. We found that Fer-1 inhibited cell death in cellular models of Huntington's disease (HD), periventricular leukomalacia (PVL), and kidney dysfunction; Fer-1 inhibited lipid peroxidation, but not mitochondrial reactive oxygen species formation or lysosomal membrane permeability. We developed a mechanistic model to explain the activity of Fer-1, which guided the development of ferrostatins with improved properties. These studies suggest numerous therapeutic uses for ferrostatins, and that lipid peroxidation mediates diverse disease phenotypes.
- Skouta, Rachid,Dixon, Scott J.,Wang, Jianlin,Dunn, Denise E.,Orman, Marina,Shimada, Kenichi,Rosenberg, Paul A.,Lo, Donald C.,Weinberg, Joel M.,Linkermann, Andreas,Stockwell, Brent R.
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p. 4551 - 4556
(2014/04/17)
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- COMPOUNDS, COMPOSITIONS, AND METHODS FOR MODULATING FERROPTOSIS AND TREATING EXCITOTOXIC DISORDERS
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The present invention provides, inter alia, a compound having the structure: (Formula (I). Also provided are compositions containing a pharmaceutically acceptable carrier and a compound according to the present invention. Further provided are methods for treating or ameliorating the effects of an excitotoxic disorder in a subject, methods of modulating ferroptosis in a subject, methods of reducing reactive oxygen species (ROS) in a cell, and methods for treating or ameliorating the effects of a neurodegenerative disease.
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Paragraph 0173; 0180: 0218
(2013/10/22)
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- Multicomponent solvent-free synthesis of benzimidazolyl imidazo[1,2-a]-pyridine under microwave irradiation
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A novel one-pot, three-component reaction employing variously substituted benzimidazole-linked amino pyridines, aldehydes, and isonitriles catalyzed by scandium(III) triflate under solvent-free conditions were accomplished. This new synthetic methodology
- Maiti, Barnali,Chanda, Kaushik,Selvaraju, Manikandan,Tseng, Chih-Chung,Sun, Chung-Ming
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p. 291 - 297
(2013/07/25)
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- Lewis acid-catalyzed formation of Ugi four-component reaction product from Passerini three-component reaction system without an added amine
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In the presence of a Lewis acid the phenol-Passerini three-component reaction (phenol-P-3CR) system is found to deliver a product of the phenol-Ugi four-component reaction (phenol-U-4CR). It is the first demonstration of an isocyanide as an amine equivale
- Dai, Wei-Min,Li, Huoming
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p. 12866 - 12876
(2008/03/28)
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- NITROGEN-CONTAINING HETEROARYL DERIVATIVES
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Disclosed are compounds, compositions and methods for treating Flaviviridae family virus infections.
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- Compounds useful for treating hepatitis C virus
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A series of compounds of Formula I are disclosed which are useful in treating viral hepatitus C. 1
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- An improved synthesis of N-substituted-2-nitroanilines
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The reaction of 2-chloronitrobenzene with substituted amines/ anilines in the presence of DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) gives N-substituted-2-nitroanilines in good to excellent yields (>75-90%).
- Chauhan,Singh, Ram,Geetanjali
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p. 2899 - 2906
(2007/10/03)
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