Discovery of a novel olefin derivative as a highly potent and selective acetyl-CoA carboxylase 2 inhibitor with in vivo efficacy.

•Novel olefin derivative as a highly potent and selective ACC2 inhibitor.•SAR optimization improved the ACC2 activity and CYP450 inhibition profile.•Compound 2e exhibited good PK profile and in vivo efficacy in C57BL/6 mice.