Piperazine oxadiazole inhibitors of acetyl-CoA carboxylase

…, A Siegmund, JG Allen, H Shu, C Fotsch…

Index: Bourbeau, Matthew P.; Siegmund, Aaron; Allen, John G.; Shu, Hong; Fotsch, Christopher; Bartberger, Michael D.; Kim, Ki-Won; Komorowski, Renee; Graham, Melissa; Busby, James; Wang, Minghan; Meyer, James; Xu, Yang; Salyers, Kevin; Fielden, Mark; Veniant, Murielle M.; Gu, Wei Journal of Medicinal Chemistry, 2013 , vol. 56, # 24 p. 10132 - 10141

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Citation Number: 6

Abstract

Acetyl-CoA carboxylase (ACC) is a target of interest for the treatment of metabolic syndrome. Starting from a biphenyloxadiazole screening hit, a series of piperazine oxadiazole ACC inhibitors was developed. Initial pharmacokinetic liabilities of the piperazine oxadiazoles were overcome by blocking predicted sites of metabolism, resulting in compounds with suitable properties for further in vivo studies. Compound 26 was shown to inhibit malonyl- ...