title: Discovery of novel 2-(pyridine-2-yl)-1H-benzimidazole derivatives as potent glucokinase activators.
abstract: The synthesis and structure-activity-relationships (SARs) of novel 2-(pyridine-2-yl)-1H-benzimidazole glucokinase activators are described. Systematic modification of benzimidazole lead 5a identified from a high-throughput screening led to the discovery of a potent and metabolically stable glucokinase activator 16p(R) with greater structural diversity from GKAs reported to date. The compound also demonstrated acute oral glucose lowering efficacy in rat OGTT model.
authors.affiliation: Banyu Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd, Okubo 3, Tsukuba 300-2611, Ibaraki, Japan. makoto.ishikawa@mochida.co.jp
authors.forename: Makoto
authors.initials: M
authors.lastname: Ishikawa
authors.forename: Katsumasa
authors.initials: K
authors.lastname: Nonoshita
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Ogino
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Nagae
authors.forename: Daisuke
authors.initials: D
authors.lastname: Tsukahara
authors.forename: Hideka
authors.initials: H
authors.lastname: Hosaka
authors.forename: Hiroko
authors.initials: H
authors.lastname: Maruki
authors.forename: Sumika
authors.initials: S
authors.lastname: Ohyama
authors.forename: Riki
authors.initials: R
authors.lastname: Yoshimoto
authors.forename: Kaori
authors.initials: K
authors.lastname: Sasaki
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Nagata
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Eiki
authors.forename: Teruyuki
authors.initials: T
authors.lastname: Nishimura
mesh_terms: D000495:Allosteric Site; D000818:Animals; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D001665:Binding Sites; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy; D015195:Drug Design; D004789:Enzyme Activation; D005941:Glucokinase / Q000378:metabolism*; D005951:Glucose Tolerance Test; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D008956:Models, Chemical; D008968:Molecular Conformation; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D001562:Benzimidazoles; D007004:Hypoglycemic Agents; C031000:benzimidazole; D005941:Glucokinase