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- W3132783161 abstract "A structure–activity relationship (SAR) study towards novel ACC1-selective inhibitors was carried out by modifying the molecular length of the linker in biaryl derivative 1 g , an ACC1/2 dual inhibitor. Ultimately, this leads us to discover novel phenoxybenzyloxy derivative 1i as a potent ACC1-selective inhibitor. Further chemical modification of this scaffold to improve cellular potency as well as physicochemical and pharmacokinetic (PK) properties produced N -2-(pyridin-2-ylethyl)acetamide derivative 1n , which showed highly potent ACC1-selective inhibition as well as sufficient PK profile for further in vivo evaluations. Oral administration of 1n significantly reduced the concentration of malonyl-CoA in HCT-116 xenograft tumors at doses of 100 mg/kg. Accordingly, our novel series of potent ACC1-selective inhibitors represents a set of useful orally-available research tools, as well as potential therapeutic agents for cancer and fatty acid-related diseases." @default.
- W3132783161 created "2021-03-01" @default.
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- W3132783161 date "2021-04-01" @default.
- W3132783161 modified "2023-09-27" @default.
- W3132783161 title "Design and synthesis of a monocyclic derivative as a selective ACC1 inhibitor by chemical modification of biphenyl ACC1/2 dual inhibitors" @default.
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- W3132783161 doi "https://doi.org/10.1016/j.bmc.2021.116056" @default.
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