title: Discovery of Chromane Propionic Acid Analogues as Selective Agonists of GPR120 within VivoActivity in Rodents.
abstract: GPR120 (FFAR4) is a fatty acid sensing G protein coupled receptor (GPCR) that has been identified as a target for possible treatment of type 2 diabetes. A selective activator of GPR120 containing a chromane scaffold has been designed, synthesized, and evaluatedin vivo. Results of these efforts suggest that chromane propionic acid18is a suitable tool molecule for further animal studies. Compound18is selective over the closely related target GPR40 (FFAR1), has a clean off-target profile, demonstrates suitable pharmacokinetic properties, and has been evaluated in wild-type/knockout GPR120 mouse oGTT studies.
authors.affiliation: Merck & Co., Inc. , West Point, Pennsylvania 19486, United States.
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Adams
authors.affiliation: Merck & Co., Inc. , Kenilworth, New Jersey 07033, United States.
authors.forename: Francisco
authors.initials: F
authors.lastname: Velazquez
authors.affiliation: Merck & Co., Inc. , Kenilworth, New Jersey 07033, United States.
authors.forename: Charles
authors.initials: C
authors.lastname: Jayne
authors.affiliation: Merck & Co., Inc. , Kenilworth, New Jersey 07033, United States.
authors.forename: Unmesh
authors.initials: U
authors.lastname: Shah
authors.affiliation: Merck & Co., Inc. , Kenilworth, New Jersey 07033, United States.
authors.forename: Shouwu
authors.initials: S
authors.lastname: Miao
authors.affiliation: Merck & Co., Inc. , Kenilworth, New Jersey 07033, United States.
authors.forename: Eric R
authors.initials: ER
authors.lastname: Ashley
authors.affiliation: Merck & Co., Inc. , Kenilworth, New Jersey 07033, United States.
authors.forename: Maria
authors.initials: M
authors.lastname: Madeira
authors.affiliation: Merck & Co., Inc. , Kenilworth, New Jersey 07033, United States.
authors.forename: Taro E
authors.initials: TE
authors.lastname: Akiyama
authors.affiliation: Merck & Co., Inc. , Kenilworth, New Jersey 07033, United States.
authors.forename: Jerry
authors.initials: J
authors.lastname: Di Salvo
authors.affiliation: WuXi AppTec , Shanghai 200131, China.
authors.forename: Takao
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: WuXi AppTec , Shanghai 200131, China.
authors.forename: Nengxue
authors.initials: N
authors.lastname: Wang
authors.affiliation: Merck & Co., Inc. , Kenilworth, New Jersey 07033, United States.
authors.forename: Quang
authors.initials: Q
authors.lastname: Truong
authors.affiliation: Merck & Co., Inc. , Kenilworth, New Jersey 07033, United States.
authors.forename: Eric
authors.initials: E
authors.lastname: Gilbert
authors.affiliation: Merck & Co., Inc. , Kenilworth, New Jersey 07033, United States.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Merck & Co., Inc. , Kenilworth, New Jersey 07033, United States.
authors.forename: Andreas
authors.initials: A
authors.lastname: Verras
authors.affiliation: Merck & Co., Inc. , Kenilworth, New Jersey 07033, United States.
authors.forename: Melissa
authors.initials: M
authors.lastname: Kirkland
authors.affiliation: Merck & Co., Inc. , Kenilworth, New Jersey 07033, United States.
authors.forename: Michele
authors.initials: M
authors.lastname: Pachanski
authors.affiliation: Merck & Co., Inc. , Kenilworth, New Jersey 07033, United States.
authors.forename: Maryann
authors.initials: M
authors.lastname: Powles
authors.affiliation: Merck & Co., Inc. , Kenilworth, New Jersey 07033, United States.
authors.forename: Wu
authors.initials: W
authors.lastname: Yin
authors.affiliation: Merck & Co., Inc. , Kenilworth, New Jersey 07033, United States.
authors.forename: Feroze
authors.initials: F
authors.lastname: Ujjainwalla
authors.affiliation: Merck & Co., Inc. , Kenilworth, New Jersey 07033, United States.
authors.forename: Srikanth
authors.initials: S
authors.lastname: Venkatraman
authors.affiliation: Merck & Co., Inc. , Kenilworth, New Jersey 07033, United States.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Edmondson
keywords: FFAR4; GPR120; chromane; insulin sensitization; type 2 diabetes