title: Discovery of canagliflozin, a novel C-glucoside with thiophene ring, as sodium-dependent glucose cotransporter 2 inhibitor for the treatment of type 2 diabetes mellitus.
abstract: We discovered that C-glucosides 4 bearing a heteroaromatic ring formed metabolically more stable inhibitors for sodium-dependent glucose cotransporter 2 (SGLT2) than the O-glucoside, 2 (T-1095). A novel thiophene derivative 4b-3 (canagliflozin) was a highly potent and selective SGLT2 inhibitor and showed pronounced anti-hyperglycemic effects in high-fat diet fed KK (HF-KK) mice.
authors.affiliation: Medicinal Chemistry Research Laboratories, Mitsubishi Tanabe Pharma Corporation, 2-2-50 Kawagishi, Toda, Saitama, Japan. nomura.sumihiro@mw.mt-pharma.co.jp
authors.forename: Sumihiro
authors.initials: S
authors.lastname: Nomura
authors.forename: Shigeki
authors.initials: S
authors.lastname: Sakamaki
authors.forename: Mitsuya
authors.initials: M
authors.lastname: Hongu
authors.forename: Eiji
authors.initials: E
authors.lastname: Kawanishi
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Koga
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Sakamoto
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Kiichiro
authors.initials: K
authors.lastname: Ueta
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Kimata
authors.forename: Keiko
authors.initials: K
authors.lastname: Nakayama
authors.forename: Minoru
authors.initials: M
authors.lastname: Tsuda-Tsukimoto
mesh_terms: D000818:Animals; D001682:Biological Availability; D000068896:Canagliflozin; D002254:Carbonates / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005960:Glucosides / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D002254:Carbonates; D005960:Glucosides; D007004:Hypoglycemic Agents; D000077203:Sodium-Glucose Transporter 2 Inhibitors; C121396:T 1095; D013876:Thiophenes; D000068896:Canagliflozin