Aglycone exploration of C-arylglucoside inhibitors of renal sodium-dependent glucose transporter SGLT2

被引：55

作者：

Ellsworth, Bruce A. ^{[1
]}

Meng, Wei ^{[1
]}

Patel, Manorama ^{[1
]}

Girotra, Ravindar N. ^{[1
]}

Wu, Gang ^{[1
]}

Sher, Philip M. ^{[1
]}

Hagan, Deborah L. ^{[1
]}

Obermeier, Mary T. ^{[1
]}

Humphreys, William G. ^{[1
]}

Robertson, James G. ^{[1
]}

Wang, Aiying ^{[1
]}

Han, Songping ^{[1
]}

Waldron, Thomas L. ^{[1
]}

Morgan, Nathan N. ^{[1
]}

Whaley, Jean M. ^{[1
]}

Washburn, William N. ^{[1
]}

机构：

[1] Bristol Myers Squibb Co, Res & Dev, Princeton, NJ 08543 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 17期

关键词：

diabetes; metabolism; glucosidase; metabolic diseases; NIDDM; C-glucoside; C-arylglucoside; SGLT; SGLT2; sodium-dependent glucose transporter; hyperglycemia; glucosuria; phlorizin; dapagliflozin;

D O I：

10.1016/j.bmcl.2008.07.109

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Inhibition of sodium-dependent glucose transporter 2 (SGLT2), the transporter that is responsible for renal re-uptake of glucose, leads to glucosuria in animals. SGLT-mediated glucosuria provides a mechanism to shed excess plasma glucose to ameliorate diabetes-related hyperglycemia and associated complications. The current study demonstrates that the proper relationship of a 4'-substituted benzyl group to a beta-1C-phenylglucoside is important for potent and selective SGLT2 inhibition. The lead C-arylglucoside (7a) demonstrates superior metabolic stability to its O-arylglucoside counterpart ( 4) and it promotes glucosuria when administered in vivo. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：4770 / 4773

页数：4

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