- Novel method for synthesizing 6-bromine-3,4-dihydro-1H-[1,8] naphthyridine-2-ketone
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The invention discloses a novel method for synthesizing 6-bromine-3,4-dihydro-1H-[1,8] naphthyridine-2-ketone and relates to the field of chemical synthesis. The method comprises the following steps:by using a four-step synthesis method, performing hydrogen substitution on a benzene ring on 2-amino-3-hydroxymethylpyridine by using bromine so as to generate 2-amino-3-hydroxymethyl-5-bromopyridine;substituting hydroxyl in the 2-amino-3-hydroxymethyl-5-bromopyridine by using chlorine in thionyl chloride so as to generate 2-amino-3-methyl chloride-5-bromopyridine hydrochloride; carrying out an annulation reaction of the 2-amino-3-methyl chloride-5-bromopyridine hydrochloride by using diethyl malonate so as to generate 6-bromine-3-nonanoic acid-ethyl ester-1,2,3,5-tetrahydro-1,8-naphthyridine-2-ketone; finally, under an alkali condition, removing carboxylic acid carbethoxy from the 6-bromine-3-nonanoic acid-ethyl ester-1,2,3,5-tetrahydro-1,8-naphthyridine-2-ketone, thereby obtaining a final product, namely 6-bromine-3,4-dihydro-1H-[1,8] naphthyridine-2-ketone. The method is low in raw material cost, simple in synthesis process, not harsh in reaction condition, safe and convenient to operate, high in final product yield, and applicable to large-scale industrial production.
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Paragraph 0028; 0030
(2018/09/12)
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- Synthesis of quinolines and naphthyridines: Via catalytic retro-aldol reaction of β-hydroxyketones with ortho -aminobenzaldehydes or nicotinaldehydes
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A Cu(i)-catalyzed retro-aldol reaction of β-hydroxyketones with ortho-aminobenzaldehydes and nicotinaldehydes is reported that produces a range of quinolines and naphthyridines with high efficiency and selectivity. This reaction uses β-hydroxyketones as a regiospecific ketone-protected enolate source via copper-catalyzed retro-aldol Cα-Cβ bond cleavage. The in situ generated copper enolate undergoes kinetically favorable cyclization with ortho-amino aryl aldehydes to produce quinolines and naphthyridines in a chemo- and regioselective manner. The mild and weakly basic reaction conditions also suppress possible side reactions of benzaldehydes under strongly basic conditions, resulting in improved reaction yields.
- Zhang, Song-Lin,Deng, Zhu-Qin
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supporting information
p. 8966 - 8970
(2016/10/05)
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- NOVEL HETEROCYCLIC ACRYLAMIDES AND THEIR USE AS PHARMACEUTICALS
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The invention relates to novel heterocyclic acrylamide compounds (I), to the preparation of the compounds and intermediates used therein, to the use of the compounds as antibacterial medicaments and pharmaceutical compositions containing the compounds.
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Page/Page column 30-31
(2011/06/19)
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- FAB I INHIBITORS
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Compounds of the formula (I) are disclosed which are Fab I inhibitors and are useful in the treatment of bacterial infections.
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- Methods of agonizing and antagonizing FabK
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The invention provides methods for using agonists and antagonists of FabK polypeptides, particularly to modulate the metabolism of bacteria or to treat bacterial infection.
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- Indole naphthyridinones as inhibitors of bacterial enoyl-ACP reductases FabI and FabK
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Bacterial enoyl-ACP reductase (FabI) is responsible for catalyzing the final step of bacterial fatty acid biosynthesis and is an attractive target for the development of novel antibacterial agents. Previously we reported the development of FabI inhibitor 4 with narrow spectrum antimicrobial activity and in vivo efficacy against Staphylococcus aureus via intraperitoneal (ip) administration. Through iterative medicinal chemistry aided by X-ray crystal structure analysis, a new series of inhibitors has been developed with greatly increased potency against FabI-containing organisms. Several of these new inhibitors have potent antibacterial activity against multidrug resistant strains of S. aureus, and compound 30 demonstrates exceptional oral (po) in vivo efficacy in a S. aureus infection model in rats. While optimizing FabI inhibitory activity, compounds 29 and 30 were identified as having low micromolar FabK inhibitory activity, thereby increasing the antimicrobial spectrum of these compounds to include the FabK-containing pathogens Streptococcus pneumoniae and Enterococcus faecalis. The results described herein support the hypothesis that bacterial enoyl-ACP reductases are valid targets for antibacterial agents.
- Seefeld, Mark A.,Miller, William H.,Newlander, Kenneth A.,Burgess, Walter J.,DeWolf Jr., Walter E.,Elkins, Patricia A.,Head, Martha S.,Jakas, Dalia R.,Janson, Cheryl A.,Keller, Paul M.,Manley, Peter J.,Moore, Terrance D.,Payne, David J.,Pearson, Stewart,Polizzi, Brian J.,Qiu, Xiayang,Rittenhouse, Stephen F.,Uzinskas, Irene N.,Wallis, Nicola G.,Huffman, William F.
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p. 1627 - 1635
(2007/10/03)
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