Vu Chi B, Milne Jill C, Carney David P, Song Jeffrey, Choy Wendy, Lambert Philip D, Gagne David J, Hirsch Michael, Cote Angela, Davis Meghan, Lainez Elden, Meade Nekeya, Normington Karl, Jirousek Michael R, Perni Robert B
Sirtris Pharmaceuticals, Departments of Medicinal Chemistry, Lead Discovery and Pharmacology, 200 Technology Square, Cambridge, MA 02139, USA.
Bioorg Med Chem Lett. 2009 Mar 1;19(5):1416-20. doi: 10.1016/j.bmcl.2009.01.044. Epub 2009 Jan 19.
A series of triamide derivatives bearing a benzothiazole core is shown to be potent microsomal triglyceride transfer protein (MTP) inhibitors. In order to minimize liver toxicity, these compounds have been optimized to have activity only in the enterocytes and have limited systemic bioavailability. Upon oral administration, selected analogs within this series have been further demonstrated to reduce food intake along with body weight and thereby improve glucose homeostasis and insulin sensitivity in a 28-day mice diet-induced obesity (DIO) model.
一系列带有苯并噻唑核心的三酰胺衍生物被证明是强效的微粒体甘油三酯转移蛋白（MTP）抑制剂。为了将肝脏毒性降至最低，这些化合物已被优化，使其仅在肠细胞中具有活性，并且全身生物利用度有限。口服给药后，该系列中的选定类似物在28天的小鼠饮食诱导肥胖（DIO）模型中进一步证明可减少食物摄入量以及体重，从而改善葡萄糖稳态和胰岛素敏感性。
