1374258-40-8Relevant academic research and scientific papers
Spirolactam-based acetyl-CoA carboxylase inhibitors: Toward improved metabolic stability of a chromanone lead structure
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.,Préville, Cathy,Banks, Tereece,Moore, Dianna E.,Mathiowetz, Alan M.,Menhaji-Klotz, Elnaz,Smith, Aaron C.,Doran, Shawn D.,Beebe, David A.,Dunn, Matthew F.
, p. 7110 - 7119 (2013)
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 improved chemical and metabolic stability relative to our previously reported pyrazoloketone series, while retaining potent inhibition of ACC1 and ACC2. Optimization of the pyrazole and amide substituents led to quinoline amide 21, which was advanced to preclinical development.
N1/N2-Lactam Acetyl-CoA carboxylase inhibitors
-
Page/Page column 36, (2012/05/07)
The invention provides a compound of Formula (I) or a pharmaceutically acceptable salt thereof; wherein G is R1, R2 and R3 are as described herein; pharmaceutical compositions thereof; and the use thereof in treating diseases, conditions or disorders modulated by the inhibition of an acetyl-CoA carboxylase enzyme(s) in an animal
