Kung Daniel W, Griffith David A, Esler William P, Vajdos Felix F, Mathiowetz Alan M, Doran Shawn D, Amor Paul A, Bagley Scott W, Banks Tereece, Cabral Shawn, Ford Kristen, Garcia-Irizarry Carmen N, Landis Margaret S, Loomis Kathrine, McPherson Kirk, Niosi Mark, Rockwell Kristin L, Rose Colin, Smith Aaron C, Southers James A, Tapley Susan, Tu Meihua, Valentine James J
Worldwide Medicinal Chemistry, Groton, CT 06340, United States.
Worldwide Medicinal Chemistry, Cambridge, MA 02139, United States.
Bioorg Med Chem Lett. 2015 Nov 15;25(22):5352-6. doi: 10.1016/j.bmcl.2015.09.035. Epub 2015 Sep 15.
A novel series of spirocyclic-diamine based, isoform non-selective inhibitors of acetyl-CoA carboxylase (ACC) is described. These spirodiamine derivatives were discovered by design of a library to mimic the structural rigidity and hydrogen-bonding pattern observed in the co-crystal structure of spirochromanone inhibitor I. The lead compound 3.5.1 inhibited de novo lipogenesis in rat hepatocytes, with an IC50 of 0.30 μM.
描述了一系列基于螺环二胺的新型乙酰辅酶A羧化酶（ACC）同工型非选择性抑制剂。这些螺二胺衍生物是通过设计一个文库发现的，以模拟在螺色满酮抑制剂I的共晶体结构中观察到的结构刚性和氢键模式。先导化合物3.5.1在大鼠肝细胞中抑制从头脂肪生成，IC50为0.30μM。
