Medicinal Chemistry Laboratories, Taisho Pharmaceutical Co, Ltd, Saitama-shi, Saitama 331-9530, Japan.
Bioorg Med Chem Lett. 2009 Dec 1;19(23):6645-8. doi: 10.1016/j.bmcl.2009.10.012. Epub 2009 Oct 8.
Acetyl-CoA carboxylases (ACCs), the rate limiting enzymes in de novo lipid synthesis, play important roles in modulating energy metabolism. The inhibition of ACC has demonstrated promising therapeutic potential for treating obesity and type 2 diabetes mellitus in transgenic mice and preclinical animal models. We describe herein the synthesis and structure-activity relationships of a series of disubstituted (4-piperidinyl)-piperazine derivatives as a new platform for ACC1/2 non-selective inhibitors.
乙酰辅酶 A 羧化酶(ACCs)是从头合成脂质过程中的限速酶,在调节能量代谢方面发挥着重要作用。在转基因小鼠和临床前动物模型中,ACCs 的抑制作用已被证明在治疗肥胖症和 2 型糖尿病方面具有很大的应用潜力。本文描述了一系列二取代(4-哌啶基)-哌嗪衍生物的合成及构效关系,为 ACC1/2 非选择性抑制剂提供了一个新的平台。