Discovery of 5-aryloxy-2,4-thiazolidinediones as potent GPR40 agonists.
Systematic structure-activity relationship (SAR) studies of a screening lead led to the discovery of a series of thiazolidinediones (TZDs) as potent GPR40 agonists. Among them, compound C demonstrated an acute mechanism-based glucose-lowering in an intraperitoneal glucose tolerance test (IPGTT) in lean mice, while no effects were observed in GPR40 knock-out mice.
Zhou
Changyou
C
Merck Research Laboratories, Rahway, NJ 07065, USA.
Tang
Cheng
C
Chang
Eric
E
Ge
Min
M
Lin
Songnian
S
Cline
Eric
E
Tan
Carina P
CP
Feng
Yue
Y
Zhou
Yun-Ping
YP
Eiermann
George J
GJ
Petrov
Aleksandr
A
Salituro
Gino
G
Meinke
Peter
P
Mosley
Ralph
R
Akiyama
Taro E
TE
Einstein
Monica
M
Kumar
Sanjeev
S
Berger
Joel
J
Howard
Andrew D
AD
Thornberry
Nancy
N
Mills
Sander G
SG
Yang
Lihu
L
D000818:Animals; D055808:Drug Discovery / Q000379:methods*; D051379:Mice; D018345:Mice, Knockout; D011485:Protein Binding / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000378:metabolism; D013329:Structure-Activity Relationship; D045162:Thiazolidinediones / Q000819:agonists / Q000737:chemistry* / Q000494:pharmacology
C473036:Ffar1 protein, mouse; D043562:Receptors, G-Protein-Coupled; D045162:Thiazolidinediones; C089946:2,4-thiazolidinedione