- Dichloroacetophenones targeting at pyruvate dehydrogenase kinase 1 with improved selectivity and antiproliferative activity: Synthesis and structure-activity relationships
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Dichloroacetophenone is a pyruvate dehydrogenase kinase 1 (PDK1) inhibitor with suboptimal kinase selectivity. Herein, we report the synthesis and biological evaluation of a series of novel dichloroacetophenones. Structure-activity relationship analyses (SARs) enabled us to identify three potent compounds, namely 54, 55, and 64, which inhibited PDK1 function, activated pyruvate dehydrogenase complex, and reduced the proliferation of NCI-H1975 cells. Mitochondrial bioenergetics assay suggested that 54, 55, and 64 enhanced the oxidative phosphorylation in cancer cells, which might contribute to the observed anti-proliferation effects. Collectively, these results suggested that 54, 55, and 64 could be promising compounds for the development of potent PDK1 inhibitors.
- Zhang, Shao-Lin,Yang, Zheng,Hu, Xiaohui,Tam, Kin Yip
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supporting information
p. 3441 - 3445
(2018/09/29)
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- SUBSTITUTED BICYCLIC HCV INHIBITORS
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Provided herein are compounds, pharmaceutical compositions and combination therapies for treatment of hepatitis C.
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Page/Page column 61-62
(2012/04/10)
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- SUBSTITUTED BICYCLIC HCV INHIBITORS
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Provided herein are compounds, pharmaceutical compositions and combination therapies for treatment of hepatitis C.
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Page/Page column 37-38
(2010/11/03)
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- A diastereoselective total synthesis of trans-trikentrin A: A ring contraction approach
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(Chemical Equation Presented) A new route to obtain the polyalkylated indole (±)-trans-trikentrin A was developed. The synthesis of this natural alkaloid features a thallium(III)-mediated ring contraction reaction to obtain the trans-1,3-disubstituted five-membered ring in a diastereoselective manner. Thallium(III) is chemoselective in this rearrangement, reacting with the olefin without oxidation of the indole moiety. Other key transformations are the Bartoli's reaction to construct the heterocyclic ring and a Heck coupling to add the carbons atom that will originate the nonaromatic cycle.
- Silva Jr., Luiz F.,Craveiro, Marcus V.
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supporting information; experimental part
p. 5417 - 5420
(2009/06/06)
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- Substituted alkylaryl ketones and methods of use as herbicides
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Ring and side chain substituted alkylaryl ketones are useful in controlling the growth of germinating and seedling weed grasses and germinating and seedling broadleaf weeds.
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