title: Discovery of 5-aryloxy-2,4-thiazolidinediones as potent GPR40 agonists.
abstract: 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.
authors.affiliation: Merck Research Laboratories, Rahway, NJ 07065, USA.
authors.forename: Changyou
authors.initials: C
authors.lastname: Zhou
authors.forename: Cheng
authors.initials: C
authors.lastname: Tang
authors.forename: Eric
authors.initials: E
authors.lastname: Chang
authors.forename: Min
authors.initials: M
authors.lastname: Ge
authors.forename: Songnian
authors.initials: S
authors.lastname: Lin
authors.forename: Eric
authors.initials: E
authors.lastname: Cline
authors.forename: Carina P
authors.initials: CP
authors.lastname: Tan
authors.forename: Yue
authors.initials: Y
authors.lastname: Feng
authors.forename: Yun-Ping
authors.initials: YP
authors.lastname: Zhou
authors.forename: George J
authors.initials: GJ
authors.lastname: Eiermann
authors.forename: Aleksandr
authors.initials: A
authors.lastname: Petrov
authors.forename: Gino
authors.initials: G
authors.lastname: Salituro
authors.forename: Peter
authors.initials: P
authors.lastname: Meinke
authors.forename: Ralph
authors.initials: R
authors.lastname: Mosley
authors.forename: Taro E
authors.initials: TE
authors.lastname: Akiyama
authors.forename: Monica
authors.initials: M
authors.lastname: Einstein
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Kumar
authors.forename: Joel
authors.initials: J
authors.lastname: Berger
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Howard
authors.forename: Nancy
authors.initials: N
authors.lastname: Thornberry
authors.forename: Sander G
authors.initials: SG
authors.lastname: Mills
authors.forename: Lihu
authors.initials: L
authors.lastname: Yang
mesh_terms: 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
chemical_list: C473036:Ffar1 protein, mouse; D043562:Receptors, G-Protein-Coupled; D045162:Thiazolidinediones; C089946:2,4-thiazolidinedione