Novel acetyl-CoA carboxylase 2 (ACC2) selective inhibitors were identified by the conversion of the alkyne unit of A-908292 to the olefin linker. Modification of the center and left part of the lead compound 1b improved the ACC2 inhibitory activity and CYP450 inhibition profile, and afforded a highly selective ACC2 inhibitor 2e which showed in vivo efficacy in C57BL/6 mice.

中文翻译：

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发现新型烯烃衍生物作为具有体内功效的高效和选择性乙酰辅酶A羧化酶2抑制剂

通过将A-908292的炔单元转化为烯烃接头，可以鉴定出新型的乙酰辅酶A羧化酶2（ACC2）选择性抑制剂。对前导化合物1b的中央和左侧部分的修饰改善了ACC2抑制活性和CYP450抑制特性，并提供了高选择性的ACC2抑制剂2e，其在C57BL / 6小鼠中显示出体内功效。