- Method for producing 2-amino-6-methylnicotinic acid
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The present invention provides a method for producing 2-amino-6-methylnicotinic acid represented by formula [I], wherein the production method comprises: (a) reacting 2-chloro-3-cyano-6-methylpyridine represented by formula [II] in an ammonia aqueous solution to obtain a reaction solution containing 2-amino-6-methylnicotinamide represented by formula [III]; and (b) removing the ammonia from the reaction solution, then reacting the 2-amino-6-methylnicotinamide represented by formula [III] with a base to produce 2-amino-6-methylnicotinic acid represented by formula [I].
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- 2-Aminonicotinic acid 1-oxides are chemically stable inhibitors of quinolinic acid synthesis in the mammalian brain: A step toward new antiexcitotoxic agents
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3-Hydroxyanthranilic acid 3,4-dioxygenase (3-HAO) is the enzyme responsible for the production of the neurotoxic tryptophan metabolite quinolinic acid (QUIN). Elevated brain levels of QUIN are observed in several neurodegenerative diseases, but pharmacological investigation on its role in the pathogenesis of these conditions is difficult because only one class of substrate-analogue 3-HAO inhibitors, with poor chemical stability, has been reported so far. Here we describe the design, synthesis, and biological evaluation of a novel class of chemically stable inhibitors based on the 2-aminonicotinic acid 1-oxide nucleus. After the preliminary in vitro evaluation of newly synthesized compounds using brain tissue homogenate, we selected the most active inhibitor and showed its ability to acutely reduce the production of QUIN in the rat brain in vivo. These findings provide a novel pharmacological tool for the study of the mechanisms underlying the onset and propagation of neurodegenerative diseases.
- Vallerini, Gian Paolo,Amori, Laura,Beato, Claudia,Tararina, Margarita,Wang, Xiao-Dan,Schwarcz, Robert,Costantino, Gabriele
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p. 9482 - 9495
(2014/01/06)
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- COMPOSITION FOR AGRICULTURAL USE FOR CONTROLLING OR PREVENTING PLANT DISEASES CAUSED BY PLANT PATHOGENS
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Disclosed is a composition for agricultural use, which is used for controlling or preventing plant diseases caused by plant pathogens. The composition for agricultural use contains a compound represented by formula (1), a salt thereof or a hydrate of the compound or the salt. (1) [In the formula, Z represents an oxygen atom, a sulfur atom or NRz; and E represents a furyl group, a thienyl group, a pyrrolyl group, a tetrazolyl group, a thiazolyl group, a pyrazolyl group, a phenyl group or the like.]
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Page/Page column 267-268
(2010/11/19)
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- Synthesis, in vitro and in vivo activity of thiamine antagonist transketolase inhibitors
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Tumor cells extensively utilize the pentose phosphate pathway for the synthesis of ribose. Transketolase is a key enzyme in this pathway and has been suggested as a target for inhibition in the treatment of cancer. In a pharmacodynamic study, nude mice with xenografted HCT-116 tumors were dosed with 1 ('N3′-pyridyl thiamine'; 3-(6-methyl-2-amino-pyridin-3-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-thiazol-3-ium chloride hydrochloride), an analog of thiamine, the co-factor of transketolase. Transketolase activity was almost completely suppressed in blood, spleen, and tumor cells, but there was little effect on the activity of the other thiamine-utilizing enzymes α-ketoglutarate dehydrogenase or glucose-6-phosphate dehydrogenase. Synthesis and SAR of transketolase inhibitors is described.
- Thomas, Allen A.,Le Huerou,De Meese,Gunawardana, Indrani,Kaplan, Tomas,Romoff, Todd T.,Gonzales, Stephen S.,Condroski, Kevin,Boyd, Steven A.,Ballard, Josh,Bernat, Bryan,DeWolf, Walter,Han, May,Lee, Patrice,Lemieux, Christine,Pedersen, Robin,Pheneger, Jed,Poch, Greg,Smith, Darin,Sullivan, Francis,Weiler, Solly,Wright, S. Kirk,Lin, Jie,Brandhuber, Barb,Vigers, Guy
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p. 2206 - 2210
(2008/12/20)
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- AKT PROTEIN KINASE INHIBITORS
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The present invention provides compounds, including resolved enantiomers, diastereomers, solvates and pharmaceutically acceptable salts thereof, comprising the Formula: A-L-CR where CR is a cyclical core group, L is a linking group and A is as defined herein. Also provided are methods of using the compounds of this invention as AKT protein kinase inhibitors and for the treatment of hyperproliferative diseases such as cancer.
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Page/Page column 145-146
(2008/06/13)
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