Novel hypoglycemic dihydropyridones serendipitously discovered from O- versus C-alkylation in the synthesis of VMAT2 antagonists

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:18

Article

Xie, Yuli¹  Raffo, Anthony¹  Ichise, Masanori²  Deng, Shixian¹  Harris, Paul E.¹  Landry, Donald W.¹ 

[1] Columbia Univ, Med Ctr, Dept Med, New York, NY 10032 USA

[2] Columbia Univ, Med Ctr, Dept Radiol, New York, NY 10032 USA

关键词: VMAT2;    hypoglycemic;    SARs;    dihydropyridone;   

DOI  :  10.1016/j.bmcl.2008.07.129

来源: Elsevier

【 摘 要 】

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. (C) 2008 Elsevier Ltd. All rights reserved.

【 授权许可】

Free