title: Aglycone exploration of C-arylglucoside inhibitors of renal sodium-dependent glucose transporter SGLT2.
abstract: 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.
authors: Research and Development, Bristol Myers Squibb Co., PO Box 5400, Princeton, NJ 08543-5400, USA.
authors: Bruce A
authors: BA
authors: Ellsworth
authors: Wei
authors: W
authors: Meng
authors: Manorama
authors: M
authors: Patel
authors: Ravindar N
authors: RN
authors: Girotra
authors: Gang
authors: G
authors: Wu
authors: Philip M
authors: PM
authors: Sher
authors: Deborah L
authors: DL
authors: Hagan
authors: Mary T
authors: MT
authors: Obermeier
authors: William G
authors: WG
authors: Humphreys
authors: James G
authors: JG
authors: Robertson
authors: Aiying
authors: A
authors: Wang
authors: Songping
authors: S
authors: Han
authors: Thomas L
authors: TL
authors: Waldron
authors: Nathan N
authors: NN
authors: Morgan
authors: Jean M
authors: JM
authors: Whaley
authors: William N
authors: WN
authors: Washburn
mesh_terms: D000818:Animals; D005947:Glucose / Q000737:chemistry; D005960:Glucosides / Q000737:chemistry* / Q000494:pharmacology*; D006030:Glycosuria, Renal / Q000188:drug therapy; D006801:Humans; D007668:Kidney / Q000187:drug effects; D051381:Rats; D051269:Sodium-Glucose Transporter 1 / Q000037:antagonists & inhibitors; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors
chemical_list: D005960:Glucosides; C089180:SLC5A2 protein, human; D051269:Sodium-Glucose Transporter 1; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D005947:Glucose