- A new and efficient method for the synthesis of 3-(2-nitrophenyl)pyruvic acid derivatives and indoles based on the Reissert reaction
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The formation of 3-(2-nitrophenyl)pyruvic acid and its amide and ester derivatives – key compounds for the Reissert indole synthesis – was achieved under various reaction conditions via the acid catalyzed hydrolysis of 5-(2-nitrobenzyliden)-2,2-dimethyl-1,3-oxazolidin-4-one, which is readily available from 3-(2-nitrophenyl)oxirane-2-carboxamide. A new and highly efficient method for the synthesis of indole-2-carboxylic acid derivatives via the intramolecular reductive cyclization of o-nitrophenylpyruvic acid and its amide and ester derivatives was developed using Na2S2O4 in dioxane/water at reflux.
- Mamedov, Vakhid A.,Mamedova, Vera L.,Syakaev, Victor V.,Khikmatova, Gul'naz Z.,Korshin, Dmitry E.,Kushatov, Temur A.,Latypov, Shamil K.
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p. 3923 - 3925
(2018/10/02)
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- Synthesis of New 1-Hydroxyindole-2-Carboxylates and Mechanistic Studies on Reaction Pathways
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Synthesis of new 1-hydroxyindole-2-carboxylates 1 and mechanistic studies on the reaction pathways were described. The substrates 2, prepared through two-step synthetic sequences, were treated with nucleophiles in the presence of SnCl2 · 2H2O to obtain compounds 1. In particular, the mechanistic studies led to a significant finding that reactions with thiol nucleophiles occur through a newly proposed pathway (path B: 1,4-addition followed by reduction/condensation) rather than through a previously assumed pathway (path A: reduction/condensation followed by 1,5-addition). Further mechanistic investigations revealed steric effects of o-substituents in 2 governing the ratio of products (1i/7).
- Park, Yeon Kyeong,Lee, Sang Hyup
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p. 1995 - 2002
(2017/05/29)
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- Synthesis of new highly substituted and hindered 1-hydroxyindole-2-carboxylates
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The synthesis of new, highly substituted, and hindered 1-hydroxyindole-2-carboxylates 1 is described. Substrates 2, prepared through a two-step synthetic sequence, were treated with relatively weak nucleophiles in the presence of SnCl2 · 2H2O to afford compounds 1. In particular, nucleophiles of low reactivity and/or high steric hindrance reacted efficiently to give 1 in good to modest yields.
- Park, Yeon Kyeong,Kim, Hyejin,Lee, Sang Hyup
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- Discovery of N-hydroxyindole-based inhibitors of human lactate dehydrogenase isoform A (LDH-A) as starvation agents against cancer cells
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Highly invasive tumor cells are characterized by a metabolic switch, known as the Warburg effect, from "normal" oxidative phosphorylation to increased glycolysis even under sufficiently oxygenated conditions. This dependence on glycolysis also confers a growth advantage to cells present in hypoxic regions of the tumor. One of the key enzymes involved in glycolysis, the muscle isoform of lactate dehydrogenase (LDH-A), is overexpressed by metastatic cancer cells and is linked to the vitality of tumors in hypoxia. This enzyme may be considered as a potential target for new anticancer agents, since its inhibition cuts cancer energetic and anabolic supply, thus reducing the metastatic and invasive potential of cancer cells. We have discovered new and efficient N-hydroxyindole-based inhibitors of LDH-A, which are isoform-selective (over LDH-B) and competitive with both the substrate (pyruvate) and the cofactor (NADH). The antiproliferative activity of these compounds was confirmed on a series of cancer cell lines, and they proved to be particularly effective under hypoxic conditions. Moreover, NMR experiments showed that these compounds are able to reduce the glucose-to-lactate conversion inside the cell.
- Granchi, Carlotta,Roy, Sarabindu,Giacomelli, Chiara,MacChia, Marco,Tuccinardi, Tiziano,Martinelli, Adriano,Lanza, Mario,Betti, Laura,Giannaccini, Gino,Lucacchini, Antonio,Funel, Nicola,León, Leticia G.,Giovannetti, Elisa,Peters, Godefridus J.,Palchaudhuri, Rahul,Calvaresi, Emilia C.,Hergenrother, Paul J.,Minutolo, Filippo
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supporting information; experimental part
p. 1599 - 1612
(2011/06/21)
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- COMPOUNDS INHIBITORS OF ENZYME LACTATE DEHYDROGENASE (LDH) AND PHARMACEUTICAL COMPOSITIONS CONTAINING THESE COMPOUNDS
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The present invention concerns compounds, some of which are novel, and their pharmaceutical applications. The compounds of the invention inhibit the enzyme lactate dehydrogenase (LDH) involved both in the metabolic process of hypoxic tumour cells, and in the process used by parasitic protozoa that cause malaria to obtain most of the energy they need.
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Page/Page column 35-36
(2011/06/11)
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- New synthetic technology for the construction of N-hydroxyindoles and synthesis of nocathiacin I model systems
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A new synthetic method providing expedient access to a wide range of polyfunctionalized N-hydroxyindoles (IV) is reported. These unique constructs are assembled by nucleophilic additions to in situ generated α,β-unsaturated nitrones (III) through carbon-carbon and carbon-heteroatom bond formation. The new synthetic technology was applied to the synthesis of nocathiacin I (1) model systems (2 and 3a-c) containing the N-hydroxyindole structural motif.
- Nicolaou,Estrada, Anthony A.,Freestone, Graeme C.,Lee, Sang Hyup,Alvarez-Mico, Xavier
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p. 6088 - 6114
(2008/02/04)
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