- Pyrano-[2,3b]-pyridines as potassium channel antagonists
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The design and synthesis of a series of highly functionalized pyrano-[2,3b]-pyridines is described. These compounds were assayed for their ability to block the IKur channel encoded by the gene hKV1.5 in patch-clamped L-929 cells. Six of the compounds in this series showed sub-micromolar activity, the most potent being 4-(4-ethyl-benzenesulfonylamino)-3-hydroxy-2,2-dimethyl-3,4-dihydro-2H-pyrano[2,3b]-pyridine-6-carboxylic acid ethyl-phenyl-amide with an IC50 of 378 nM.
- Finlay, Heather J.,Lloyd, John,Nyman, Michael,Conder, Mary Lee,West, Tonya,Levesque, Paul,Atwal, Karnail
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p. 2714 - 2718
(2008/12/21)
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- Method of manufacturing flumetralin
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The invention is a process to manufacture the intermediate secondary amine N-ethyl-2-chloro-6-fluoro-benzylamine, and then the process of reacting this intermediate to manufacture the herbicide flumetralin. Equimolar quantities of monoethylamine, sodium hydroxide, and 2-chloro-6-fluorobenzyl chloride are reacted at a temperature between about 70 DEG C. and about 100 DEG C. in a composition containing at least 2.5 times the required quantity of monoethylamine. The reagent monoethylamine functions as solvent and heat sink for the reaction, and also minimizes the formation of undesired byproducts. The excess monoethylamine is removed after formation of the intermediate. Then, equimolar quantities of sodium hydroxide in water and molten 4-chloro-3-5-dinitrobenzotrifluoride are added to the intermediate, and the temperature is controlled between about 90 DEG C. and about 115 DEG C. The product of this reaction is relatively pure, i.e., 98 percent by weight, molten flumetralin. It is advantageous to wash the product with boiling water to facilitate removal of salt and excess sodium hydroxide.
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