Xie Yuli, Raffo Anthony, Ichise Masanori, Deng Shixian, Harris Paul E, Landry Donald W
Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA.
Bioorg Med Chem Lett. 2008 Sep 15;18(18):5111-4. doi: 10.1016/j.bmcl.2008.07.129. Epub 2008 Aug 7.
Vesicular monoamine transporter type 2 (VMAT2) is a newly emerging target for both diagnostic and therapeutic applications in diabetes mellitus. In pursuit of novel VMAT2 antagonists, we identified a potent hypoglycemic agent with a novel dihydropyridone scaffold. Several analogs were designed and synthesized. A preliminary structure activity relationship (SAR) showed that the dihydropyridone scaffold is required for the activity.
囊泡单胺转运体2(VMAT2)是糖尿病诊断和治疗应用中一个新出现的靶点。为了寻找新型VMAT2拮抗剂,我们鉴定出一种具有新型二氢吡啶骨架的强效降血糖药物。设计并合成了几种类似物。初步的构效关系(SAR)表明,二氢吡啶骨架是活性所必需的。