Bioorganic & Medicinal Chemistry 2011-09-15

Novel macrocyclic C-aryl glucoside SGLT2 inhibitors as potential antidiabetic agents.

Min Ju Kim, Suk Ho Lee, So Ok Park, Hyunku Kang, Jun Sung Lee, Ki Nam Lee, Myung Eun Jung, Jeongmin Kim, Jinhwa Lee

Index: Bioorg. Med. Chem. 19(18) , 5468-79, (2011)

Full Text: HTML

Abstract

Novel macrocyclic C-aryl glucoside SGLT2 inhibitors were designed and synthesized. Two different synthetic routes of macrocyclization were adopted to prepare novel ansa SGLT2 inhibitors. Among the compounds tested, [1,7]dioxacyclopentadecine macrocycles possessing methylthiophenyl at the distal ring 40 or ethoxyphenyl at the distal ring 23 showed the best in vitro inhibitory activity in this series to date (40, IC(50)=0.778 nM and 23, IC(50)=0.899 nM) against hSGLT2.Copyright © 2011 Elsevier Ltd. All rights reserved.