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Design, Synthesis, and Molecular Docking Study of Flavonol Derivatives as Selective JAK1 Inhibitors
Design, Synthesis, and Molecular Docking Study of Flavonol Derivatives as Selective JAK1 Inhibitors
Bulletin of the Korean Chemical Society. 2014. Aug, 35(8): 2581-2584
Copyright © 2014, Korea Chemical Society
  • Received : April 24, 2014
  • Accepted : April 28, 2014
  • Published : August 20, 2014
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Mi Kyoung Kim
Onnuri Bae
Youhoon Chong

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Experimental Section
Preparation of the Title Compound 2b. To a stirred suspension of 2′-hydroxyacetophenone ( 4 ) (1 g, 2.3 mmol) in dichloromethane (10 mL) was added EDC (881 mg, 4.6 mmol) followed by DMAP (562 mg, 4.6 mmol). Upon complete dissolution, benzoic acid 6b (2.3 mmol) was added. The mixture was stirred at rt for 4 h and concentrated under reduced pressure. The ester (7) (2.3 mmol) thus obtained was dissolved in toluene (10 mL), and the resulting solution was treated with K 2 CO 3 (636 mg, 4.6 mmol) and tetra-n-butylammonium bromide (741 mg, 2.3 mmol). After stirring for 3 h at 90 ℃, solid materials were removed by filtration, and the filtrate was concentrated under reduced pressure. The crude compound obtained above was dissolved in MeOH (5 mL), and the resulting solution was treated with p -TsOH (10 mmol) at 0 ℃. The reaction mixture was stirred for 4 h at room temperature, and then concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (2:1 = Hex:Acetone) to give 2-(2-(3-hydroxyprop-1-yn-1-yl)-5-(3,5,7-trihydroxy-4-oxo-4Hchromen-2-yl)phenyl) acetonitrile ( 2b ) as yellow powder: 1H NMR (400 MHz, Acetone- d 6 ) δ 12.8 (s, OH), 7.42 (d, J = 8.4 Hz, 1H), 7.27 (d, J = 2.0 Hz, 1H), 7.12 (dd, J = 2.1, 8.4 Hz, 1H), 6.44 (d, J = 2.1 Hz, 1H), 6.40 (d, J = 2.2 Hz, 1H), 4.42 (s, 2H), 4.12 (s, 2H); 13 C NMR (100 MHz, DMSO- d 6 ) δ 176.1, 166.7, 161.8, 160.3, 147.2, 136.6, 133.5, 130.2, 128.1, 126.9, 125.9, 122.3, 117.8, 104.8, 99.5, 95.1, 98.6, 88.4, 52.6, 23.5.
Acknowledgements
This research was supported by a grant from the Korean Health Technology R&D project, Ministry of Health & Welfare, Republic of Korea (A111698), by the Priority Research Centers Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2009-0093824), and by a grant from Next Generation Bio-Green 21 PJ007982 (Korea Rural Development Administration).
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