N-glucosides as human sodium-dependent glucose cotransporter 2 (hSGLT2) inhibitors

被引：22
|
作者：
Yamamoto, Yasuo [1 ]
Kawanishi, Eiji [1 ]
Koga, Yuichi [1 ]
Sakamaki, Shigeki [1 ]
Sakamoto, Toshiaki [1 ]
Ueta, Kiichiro [2 ]
Matsushita, Yasuaki [2 ]
Kuriyama, Chiaki [2 ]
Tsuda-Tsukimoto, Minoru [3 ]
Nomura, Sumihiro [1 ]
机构：
[1] Mitsubishi Tanabe Pharma Corp, Med Chem Res Labs, Toda, Saitama 3358505, Japan
[2] Mitsubishi Tanabe Pharma Corp, Pharmacol Res Labs, Toda, Saitama 3358505, Japan
[3] Mitsubishi Tanabe Pharma Corp, DMPK Res Labs, Toda, Saitama 3358505, Japan
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2013年 / 23卷 / 20期
关键词：
SGLT2; Sodium-dependent glucose cotransporter; Diabetes; Glucoside; N-glucoside; NA+/GLUCOSE COTRANSPORTER; DIABETES-MELLITUS; SGLT2; INHIBITORS; MECHANISM; TYPE-2; REABSORPTION; DISCOVERY; POTENT; RING;
D O I：
10.1016/j.bmcl.2013.08.042
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Inhibition of renal sodium-dependent glucose cotransporter 2 (SGLT2) increases urinary glucose excretion (UGE), and thus reduces blood glucose levels in hyperglycemia. A series of N-glucosides was synthesized for biological evaluation as human SGLT2 (hSGLT2) inhibitors. Among these compounds, N-glucoside 9d possessing an indole core structure showed good in vitro activity (IC50 = 7.1 nM against hSGLT2). Furthermore, 9d exhibited favorable in vivo potency with regard to UGE in rats based on good pharmacokinetic profiles. (C) 2013 Elsevier Ltd. All rights reserved.
引用
收藏
页码：5641 / 5645
页数：5
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