Discovery and structure-activity relationships of a novel class of quinazoline glucokinase activators.
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).
Iino
Tomoharu
T
Banyu Tsukuba Research Institute, Banyu Pharmaceutical Co. Ltd, Okubo-3, Tsukuba 300-2611, Ibaraki, Japan. tomoharu_iino@merck.com
Sasaki
Yasuhiro
Y
Bamba
Makoto
M
Mitsuya
Morihiro
M
Ohno
Akio
A
Kamata
Kenji
K
Hosaka
Hideka
H
Maruki
Hiroko
H
Futamura
Mayumi
M
Yoshimoto
Riki
R
Ohyama
Sumika
S
Sasaki
Kaori
K
Chiba
Masato
M
Ohtake
Norikazu
N
Nagata
Yasufumi
Y
Eiki
Jun-Ichi
J
Nishimura
Teruyuki
T
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
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D011799:Quinazolines; D005941:Glucokinase