title: N-Glucosides as human sodium-dependent glucose cotransporter 2 (hSGLT2) inhibitors.
abstract: 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.
authors.affiliation: Medicinal Chemistry Research Laboratories, Mitsubishi Tanabe Pharma Corporation, 2-2-50 Kawagishi, Toda, Saitama 335-8505, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Eiji
authors.initials: E
authors.lastname: Kawanishi
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Koga
authors.forename: Shigeki
authors.initials: S
authors.lastname: Sakamaki
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Sakamoto
authors.forename: Kiichiro
authors.initials: K
authors.lastname: Ueta
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Matsushita
authors.forename: Chiaki
authors.initials: C
authors.lastname: Kuriyama
authors.forename: Minoru
authors.initials: M
authors.lastname: Tsuda-Tsukimoto
authors.forename: Sumihiro
authors.initials: S
authors.lastname: Nomura
mesh_terms: D000818:Animals; D005947:Glucose / Q000378:metabolism; D005960:Glucosides / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D006207:Half-Life; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D011485:Protein Binding; D051381:Rats; D051297:Sodium-Glucose Transporter 2 / Q000378:metabolism; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013329:Structure-Activity Relationship
chemical_list: C588140:3-(4-ethylphenylmethyl)-1-(glucopyranosyl)indole; D005960:Glucosides; D007211:Indoles; C089180:SLC5A2 protein, human; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D005947:Glucose
keywords: Diabetes; Glucoside; N-glucoside; SGLT2; Sodium-dependent glucose cotransporter