Lead Generation Department, AstraZeneca R&D Mölndal, S-431 83 Mölndal, Sweden.
Bioorg Med Chem Lett. 2010 Jan 15;20(2):479-82. doi: 10.1016/j.bmcl.2009.11.125. Epub 2009 Nov 27.
A novel class of cannabinoid-1 (CB1) receptor antagonists for the treatment of obesity is presented. The carboxamide linker in a set of 5,6-diaryl-pyrazine-2-amide derivatives was transformed into the corresponding thioamide, by using a one-pot synthesis. The structural series of thioamides not only showed retained CB1 potency (below 10nM), but also showed improved solubility. In addition, the neutral antagonist 2c significantly reduced body weight in cafeteria diet obese mice.
本文介绍了一类新型的大麻素-1（CB1）受体拮抗剂，可用于治疗肥胖症。通过一锅合成的方法，将一组 5,6-二芳基吡嗪-2-甲酰胺衍生物中的羧酰胺连接基转化为相应的硫代酰胺。硫代酰胺结构系列不仅保持了 CB1 的效力（低于 10nM），而且还提高了其溶解度。此外，中性拮抗剂 2c 可显著降低 cafeteria 饮食肥胖小鼠的体重。
