- 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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- α-Halogenation of carbonyl compounds: Halotrimethylsilane-nitrate salt couple as an efficient halogenating reagent system
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A mixture of chloro/bromotrimethylsilane and nitrate salt is found to be an effective reagent system for the α-chlorination/bromination of carbonyl compounds. The reaction occurs under mild conditions yielding the products in moderate to good yields.
- Prakash, G.K. Sxurya,Ismail, Rehana,Garcia, Jessica,Panja, Chiradeep,Rasul, Golam,Mathew, Thomas,Olah, George A.
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experimental part
p. 1217 - 1221
(2011/03/22)
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- Preparation of carbon-14 labeled organophosphate pesticides: Chlorfenvinphos
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Synthesis of [vinyl-14C]chlorfenvinphos, utilizing [14C]iodomethane as the source of the label, was accomplished in 28% radiochemical yield by the methylation of 2,4-dichlorobenzoyl chloride, chlorination of the resulting [14C]-2,4-dichloroacetophenone, and condensation of the product with triethylphosphite. The product, isolated as a mixture of E and Z isomere (3.6 and 96.3%, respectively), was obtained in >99% purity and had specific activity 20 mCl/mmol.
- Fudala, Louise,Lewin, Anita H.
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p. 261 - 266
(2007/10/03)
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- Halogenation Using Quaternary Ammonium Polyhalides. XXXII. Dichlorination of Aromatic Acetyl Derivatives with Benzyltrimethylammonium Tetrachloroiodate
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The reaction of aromatic acetyl derivatives with 2 molar amounts of benzyltrimethylammonium tetrachloroiodate in acetic acid at 70 deg C for several hours gave dichloroacetyl derivatives in good yields.
- Kakinami, Takaaki,Urabe, Yasuaki,Hermawan, Irwan,Yamanishi, Hiroko,Okamoto, Tsuyoshi,Kajigaeshi, Shoji
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p. 2549 - 2551
(2007/10/02)
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- NOVEL FRIEDEL-CRAFTS REACTIONS OF SOME ARENES
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The novel secondary Friedel-Crafts acylation products of the arenes, dimethyl resorcinol, m-xylene, m-methylanisole and m-chlorotoluene using dichloroacetylchloride and anhydrous AlCl3 are described.The formation of the unexpected products has been shown to depend on the nucleophilicity of the arene and the electrophilicity of the acyl carbonyl of the initially formed acylated product.Higher molar proportion of the arene and sometimes elevated temperature are necessary for generation of the products.The reaction pathway has been shown to be influenced by the formation of the possible complex of AlCl3 and dichloroacetylchloride with the groups adjacent to the dichloroacetyl function, especially at higher temperature.Dimethylresorcinol yields the unique products 4, 5, 6, 7 and 9 and m-xylene, m-methylanisole and m-chlorotoluene furnish 10, 13 and 15 respectively.Electronic factors responsible for generation of the products and rationalisation of their formation are discussed.
- Mahato, Shashi B.,Mandal, Nirup B.,Pal, Anil K.,Maitra, Swapan K.
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p. 4439 - 4446
(2007/10/02)
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