Spirolactam-based acetyl-CoA carboxylase inhibitors: toward improved metabolic stability of a chromanone lead structure

…, J Polivkova, D Zeng, CN Garcia-Irizarry…

Index: Griffith, David A.; Dow, Robert L.; Huard, Kim; Edmonds, David J.; Bagley, Scott W.; Polivkova, Jana; Zeng, Dongxiang; Garcia-Irizarry, Carmen N.; Southers, James A.; Esler, William; Amor, Paul; Loomis, Kathrine; McPherson, Kirk; Bahnck, Kevin B.; Preville, Cathy; Banks, Tereece; Moore, Dianna E.; Mathiowetz, Alan M.; Menhaji-Klotz, Elnaz; Smith, Aaron C.; Doran, Shawn D.; Beebe, David A.; Dunn, Matthew F. Journal of Medicinal Chemistry, 2013 , vol. 56, # 17 p. 7110 - 7119

Full Text: HTML

Citation Number: 11

Abstract

Acetyl-CoA carboxylase (ACC) catalyzes the rate-determining step in de novo lipogenesis and plays a crucial role in the regulation of fatty acid oxidation. Alterations in lipid metabolism are believed to contribute to insulin resistance; thus inhibition of ACC offers a promising option for intervention in type 2 diabetes mellitus. Herein we disclose a series of ACC inhibitors based on a spirocyclic pyrazololactam core. The lactam series has ...