title: Novel macrocyclic C-aryl glucoside SGLT2 inhibitors as potential antidiabetic agents.
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.
authors.affiliation: Research Center, Green Cross Corporation, 303 Bojeong-Dong, Giheung-Gu, Yongin, Gyeonggi-Do 446-770, Republic of Korea.
authors.forename: Min Ju
authors.initials: MJ
authors.lastname: Kim
authors.forename: Suk Ho
authors.initials: SH
authors.lastname: Lee
authors.forename: So Ok
authors.initials: SO
authors.lastname: Park
authors.forename: Hyunku
authors.initials: H
authors.lastname: Kang
authors.forename: Jun Sung
authors.initials: JS
authors.lastname: Lee
authors.forename: Ki Nam
authors.initials: KN
authors.lastname: Lee
authors.forename: Myung Eun
authors.initials: ME
authors.lastname: Jung
authors.forename: Jeongmin
authors.initials: J
authors.lastname: Kim
authors.forename: Jinhwa
authors.initials: J
authors.lastname: Lee
mesh_terms: D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D003500:Cyclization; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D005960:Glucosides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D047028:Macrocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008968:Molecular Conformation; D051297:Sodium-Glucose Transporter 2 / Q000235:genetics / Q000378:metabolism; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D005960:Glucosides; D007004:Hypoglycemic Agents; D047028:Macrocyclic Compounds; C089180:SLC5A2 protein, human; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors