Glucokinase-activating ureas.
The synthesis, SAR and biological evaluation of a series of ureas that activate glucokinase, a target for diabetes therapy as a result of its critical role in the regulation of whole-body glucose homeostasis, are described. Some of the urea-containing glucokinase activators lowered blood glucose levels in vivo following oral dosing to C57BL/6J mice.
Castelhano
Arlindo L
AL
OSI Pharmaceuticals, 1 Bioscience Park Drive, Farmingdale, NY 11735, USA.
Dong
Hanqing
H
Fyfe
Matthew C T
MC
Gardner
Lisa S
LS
Kamikozawa
Yukari
Y
Kurabayashi
Satomi
S
Nawano
Masao
M
Ohashi
Rikiya
R
Procter
Martin J
MJ
Qiu
Li
L
Rasamison
Chrystelle M
CM
Schofield
Karen L
KL
Shah
Vilas K
VK
Ueta
Kiichiro
K
Williams
Geoffrey M
GM
Witter
David
D
Yasuda
Kosuke
K
D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005941:Glucokinase / Q000187:drug effects* / Q000378:metabolism*; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology*
D001786:Blood Glucose; D014508:Urea; D005941:Glucokinase