title: Discovery and structure-activity relationships of a novel class of quinazoline glucokinase activators.
abstract: We describe design, syntheses and structure-activity relationships of a novel class of 4,6-disubstituted quinazoline glucokinase activators. Prototype quinazoline leads (4 and 5) were designed based on the X-ray analyses of the previous 2-aminobenzamide lead classes. Modifications of the quinazoline leads led to the identification of a potent GK activator (21d).
authors.affiliation: Banyu Tsukuba Research Institute, Banyu Pharmaceutical Co. Ltd, Okubo-3, Tsukuba 300-2611, Ibaraki, Japan. tomoharu_iino@merck.com
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Iino
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Makoto
authors.initials: M
authors.lastname: Bamba
authors.forename: Morihiro
authors.initials: M
authors.lastname: Mitsuya
authors.forename: Akio
authors.initials: A
authors.lastname: Ohno
authors.forename: Kenji
authors.initials: K
authors.lastname: Kamata
authors.forename: Hideka
authors.initials: H
authors.lastname: Hosaka
authors.forename: Hiroko
authors.initials: H
authors.lastname: Maruki
authors.forename: Mayumi
authors.initials: M
authors.lastname: Futamura
authors.forename: Riki
authors.initials: R
authors.lastname: Yoshimoto
authors.forename: Sumika
authors.initials: S
authors.lastname: Ohyama
authors.forename: Kaori
authors.initials: K
authors.lastname: Sasaki
authors.forename: Masato
authors.initials: M
authors.lastname: Chiba
authors.forename: Norikazu
authors.initials: N
authors.lastname: Ohtake
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: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D055808:Drug Discovery; D005941:Glucokinase / Q000737:chemistry* / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051379:Mice; D011799:Quinazolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D011799:Quinazolines; D005941:Glucokinase