Identification of novel and potent 2-amino benzamide derivatives as allosteric glucokinase activators.
The identification and structure-activity-relationships (SARs) of novel 2-amino benzamide glucokinase activators are described. Compounds in this series were developed to be potent GK activators, and their binding mode to the GK protein was determined by crystal structure analysis. In vivo pharmacokinetic and acute in vivo efficacy studies of compound 18 are also described.
Nishimura
Teruyuki
T
Banyu Tsukuba Research Institute, Banyu Pharmaceutical Co. Ltd., Okubo-3, Tsukuba, 300-2611 Ibaraki, Japan.
Iino
Tomoharu
T
Mitsuya
Morihiro
M
Bamba
Makoto
M
Watanabe
Hitomi
H
Tsukahara
Daisuke
D
Kamata
Kenji
K
Sasaki
Kaori
K
Ohyama
Sumika
S
Hosaka
Hideka
H
Futamura
Mayumi
M
Nagata
Yasufumi
Y
Eiki
Jun-Ichi
J
D000494:Allosteric Regulation / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001549:Benzamides / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D005941:Glucokinase / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
D001549:Benzamides; D005941:Glucokinase