- Synthesis and anti-staphylococcal activity of novel bacterial topoisomerase inhibitors with a 5-amino-1,3-dioxane linker moiety
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Novel bacterial type II topoisomerase inhibitors (NBTIs) constitute a promising new class of antibacterial agents. We report a series of NBTIs with potent anti-staphylococcal activity and diminished hERG inhibition. Dioxane-linked compound 9 demonstrated MICs ≤1 μg/mL against both methicillin-susceptible (MSSA) and -resistant Staphylococcus aureus (MRSA), accompanied by reduced hERG inhibition as compared to cyclohexane- or piperidine-linked analogs.
- Li, Linsen,Okumu, Antony,Dellos-Nolan, Sheri,Li, Zoe,Karmahapatra, Soumendrakrishna,English, Anthony,Yalowich, Jack C.,Wozniak, Daniel J.,Mitton-Fry, Mark J.
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Read Online
- TYPE II TOPOISOMERASE INHIBITORS AND METHODS OF MAKING AND USING THEREOF
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Disclosed are Type II Topoisomerase Inhibitors, analogs thereof, pharmaceutical compositions thereof, and methods of making and using these compounds and compositions. Methods of using the disclosed compounds to treat infections, such as MRSA, MDR P. aeruginosa, and other pathogens are also described.
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Page/Page column 44; 45
(2018/11/22)
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- Direct access of the chiral quinolinyl core of cinchona alkaloids via a br?nsted acid and chiral amine co-catalyzed chemo- and enantioselective α-alkylation of quinolinylmethanols with enals
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A strategy for the facile construction of the chiral quinolinylmethanolic structure, a core featured in cinchona alkaloids, is reported. A new reactivity is harnessed by TfOH-promoted chemoselective activation of α-C-H over O-H bond in quinolinylmethanols. The new reactivity is successfully engineered with an iminium catalysis in a synergistic manner to create a powerful conjugate addition-cyclization cascade process for synthesis of chiral quinoline derived π-butyrolactones in good yields and with good to excellent enantioselectivities. The method enables the first total synthesis of natural product broussonetine in three steps.
- Tong, Mengchao,Wang, Sinan,Zhuang, Jinchen,Qin, Cong,Li, Hao,Wang, Wei
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supporting information
p. 1195 - 1199
(2018/02/23)
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- The design, synthesis, in silico ADME profiling, antiplasmodial and antimycobacterial evaluation of new arylamino quinoline derivatives
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A series of new arylamino quinoline derivatives was designed based on the quinine and mefloquine scaffolds and evaluated in vitro for antiplasmodial and antimycobacterial activities. A number of these compounds exhibited significant activity against the d
- Tukulula, Matshawandile,Little, Susan,Gut, Jiri,Rosenthal, Philip J.,Wan, Baojie,Franzblau, Scott G.,Chibale, Kelly
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p. 259 - 267
(2013/01/15)
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- Flexible palladium-catalysed amidation reactions for the synthesis of complex aryl amides
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This Letter describes the synthesis of complex aryl amides using palladium-catalysed amidation reactions. Use of these conditions allowed for the coupling of a variety of aryl halides and triflates with a host of primary amides in high yields.
- Barfoot, Christopher,Brooks, Gerald,Brown, Pamela,Dabbs, Steven,Davies, David T.,Giordano, Ilaria,Hennessy, Alan,Jones, Graham,Markwell, Roger,Miles, Timothy,Pearson, Neil,Smethurst, Christian A.
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body text
p. 2685 - 2689
(2010/06/21)
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- From serendipity to rational antituberculosis drug discovery of mefloquine-isoxazole carboxylic acid esters
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Both in vitro and in vivo metabolism studies suggested that 5-(2,8-bis(trifluoromethyl)quinolin-4-yloxymethyl)isoxazole-3-carboxylic acid ethyl ester (compound 3) with previously reported antituberculosis activity is rapidly converted to two metabolites 3
- Mao, Jialin,Yuan, Hai,Wang, Yuehong,Wan, Baojie,Pieroni, Marco,Huang, Qingqing,Van Breemen, Richard B.,Kozikowski, Alan P.,Franzblau, Scott G.
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experimental part
p. 6966 - 6978
(2010/08/20)
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- Novel pyrazole derivatives as potent inhibitors of type II topoisomerases. Part 1: Synthesis and preliminary SAR analysis
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In an attempt to search for a new class of antibacterial agents, we have discovered a series of pyrazole analogs that possess good antibacterial activity for Gram-positive and Gram-negative organisms via inhibition of type II bacterial topoisomerases. We have investigated the structure-activity relationships of this series, with an emphasis on the length and conformation of the linker. This work led to the identification of tetrahydroindazole analogs, such as compound 1, as the most potent class of compounds.
- Gomez, Laurent,Hack, Michael D.,Wu, Jiejun,Wiener, John J.M.,Venkatesan, Hari,Santillan Jr., Alejandro,Pippel, Daniel J.,Mani, Neelakandha,Morrow, Brian J.,Motley, S. Timothy,Shaw, Karen Joy,Wolin, Ronald,Grice, Cheryl A.,Jones, Todd K.
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p. 2723 - 2727
(2008/02/03)
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- ANTIBACTERIAL AGENTS
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Naphthalene, quinoline, quinoxaline and naphthyridine derivatives useful in the treatment of bacterial infections in mammals, particularly humans, are disclosed herein.
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Page/Page column 31
(2010/11/25)
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- Bicyclic pyrazole compounds as antibacterial agents
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Antibacterial compounds, compositions containing them, and methods of use for the inhibition of bacterial activity and the treatment, prevention or inhibition of bacterial infection.
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Page/Page column 20
(2010/11/24)
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- ANTIBACTERIAL AGENTS
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Naphthalene, quinoline, quinoxaline and naphthyridine derivatives useful in the treatment of bacterial infections in mammals, particularly humans, are disclosed herein.
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Page/Page column 77
(2010/02/15)
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- Catalytic Asymmetric Total Syntheses of Quinine and Quinidine
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The catalytic, asymmetric syntheses of quinine and quinidine were achieved in 16 steps. The recently developed salen(Al)-catalyzed enantioselective Michael addition of methyl cyanoacetate served to set the crucial C4 stereocenter in 92% ee, and a late-stage asymmetric dihydroxylation was used to differentiate the common intermediate and access the two desired diastereomeric products with high selectivity. Copyright
- Raheem, Izzat T.,Goodman, Steven N.,Jacobsen, Eric N.
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p. 706 - 707
(2007/10/03)
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