title: Discovery of Ipragliflozin (ASP1941): a novel C-glucoside with benzothiophene structure as a potent and selective sodium glucose co-transporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes mellitus.
abstract: A series of C-glucosides with various heteroaromatics has been synthesized and its inhibitory activity toward SGLTs was evaluated. Upon screening several compounds, the benzothiophene derivative (14a) was found to have potent inhibitory activity against SGLT2 and good selectivity versus SGLT1. Through further optimization of 14a, a novel benzothiophene derivative (14h; ipragliflozin, ASP1941) was discovered as a highly potent and selective SGLT2 inhibitor that reduced blood glucose levels in a dose-dependent manner in diabetic models KK-A(y) mice and STZ rats.
authors.affiliation: Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. masakazu.imamura@astellas.com
authors.forename: Masakazu
authors.initials: M
authors.lastname: Imamura
authors.forename: Keita
authors.initials: K
authors.lastname: Nakanishi
authors.forename: Takayuki
authors.initials: T
authors.lastname: Suzuki
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ikegai
authors.forename: Ryota
authors.initials: R
authors.lastname: Shiraki
authors.forename: Takashi
authors.initials: T
authors.lastname: Ogiyama
authors.forename: Takeshi
authors.initials: T
authors.lastname: Murakami
authors.forename: Eiji
authors.initials: E
authors.lastname: Kurosaki
authors.forename: Atsushi
authors.initials: A
authors.lastname: Noda
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yokota
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Koide
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kosakai
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Ohkura
authors.forename: Makoto
authors.initials: M
authors.lastname: Takeuchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tomiyama
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Ohta
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects*; D016466:CHO Cells; D006224:Cricetinae; D003924:Diabetes Mellitus, Type 2; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005960:Glucosides / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008297:Male; D051379:Mice; D015394:Molecular Structure; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D001786:Blood Glucose; D005960:Glucosides; D007004:Hypoglycemic Agents; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013876:Thiophenes; C572941:ipragliflozin