Discovery of 3,5-Dimethylpyridin-4(1H)-one Derivatives as Activators of AMP-Activated Protein Kinase (AMPK)

Novel 3,5-dimethylpyridin-4(1H)-one scaffold compounds were synthesized and evaluated as AMP-activated protein kinase (AMPK) activators. Unlike direct AMPK activators, this series of compounds showed selective cell growth inhibitory activity against human breast cancer cell lines. By optimizing the...

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Bibliographic Details
Published inChemical and Pharmaceutical Bulletin Vol. 68; no. 1; pp. 77 - 90
Main Authors Kazuyuki Kuramoto, Yuki Sawada, Naoki Ishibashi, Tomohiro Yamada, Takeyuki Nagashima, Takashi Shin
Format Journal Article
LanguageJapanese
Published Pharmaceutical Society of Japan 01.01.2020
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Summary:Novel 3,5-dimethylpyridin-4(1H)-one scaffold compounds were synthesized and evaluated as AMP-activated protein kinase (AMPK) activators. Unlike direct AMPK activators, this series of compounds showed selective cell growth inhibitory activity against human breast cancer cell lines. By optimizing the lead compound (4a) from our library, 2-[({1'-[(4-fluorophenyl)methyl]-2-methyl-1',2',3',6'-tetrahydro[3,4'-bipyridin]-6-yl}oxy)methyl]-3,5-dimethylpyridin-4(1H)-one (25) was found to have potent AMPK activating activity. Compound 25 also showed good aqueous solubility while maintaining the unique selectivity in cell growth inhibitory activity.
ISSN:0009-2363
1347-5223