基于哌啶-芳基脲的硬脂酰辅酶A去饱和酶1抑制剂的发现。
Discovery of piperidine-aryl urea-based stearoyl-CoA desaturase 1 inhibitors.
作者信息
Xin Zhili, Zhao Hongyu, Serby Michael D, Liu Bo, Liu Mei, Szczepankiewicz Bruce G, Nelson Lissa T J, Smith Harriet T, Suhar Tom S, Janis Rich S, Cao Ning, Camp Heidi S, Collins Christine A, Sham Hing L, Surowy Teresa K, Liu Gang
机构信息
Abbott Laboratories, Global Pharmaceutical Research and Development, 100 Abbott Road, Abbott Park, IL 60064, USA.
出版信息
Bioorg Med Chem Lett. 2008 Aug 1;18(15):4298-302. doi: 10.1016/j.bmcl.2008.06.088. Epub 2008 Jun 28.
A series of structurally novel stearoyl-CoA desaturase1 (SCD1) inhibitors has been identified via molecular scaffold manipulation. Preliminary structure-activity relationship (SAR) studies led to the discovery of potent, and orally bioavailable piperidine-aryl urea-based SCD1 inhibitors. 4-(2-Chlorophenoxy)-N-[3-(methyl carbamoyl)phenyl]piperidine-1-carboxamide 4c exhibited robust in vivo activity with dose-dependent desaturation index lowering effects.
通过分子骨架操纵，已鉴定出一系列结构新颖的硬脂酰辅酶A去饱和酶1（SCD1）抑制剂。初步的构效关系（SAR）研究促成了强效且口服生物可利用的基于哌啶-芳基脲的SCD1抑制剂的发现。4-(2-氯苯氧基)-N-[3-(甲基氨基甲酰基)苯基]哌啶-1-甲酰胺4c表现出强大的体内活性，具有剂量依赖性的去饱和指数降低作用。
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