title: Discovery and optimization of arylsulfonyl 3-(pyridin-2-yloxy)anilines as novel GPR119 agonists.
abstract: We describe the discovery of a series of arylsulfonyl 3-(pyridin-2-yloxy)anilines as GPR119 agonists derived from compound 1. Replacement of the three methyl groups in 1 with metabolically stable moieties led to the identification of compound 34, a potent and efficacious GPR119 agonist with improved pharmacokinetic (PK) properties.
authors: Department of Therapeutic Discovery, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA. jian@amgen.com
authors: Jian Ken
authors: JK
authors: Zhang
authors: An-Rong
authors: AR
authors: Li
authors: Ming
authors: M
authors: Yu
authors: Yingcai
authors: Y
authors: Wang
authors: Jiang
authors: J
authors: Zhu
authors: Frank
authors: F
authors: Kayser
authors: Julio C
authors: JC
authors: Medina
authors: Karen
authors: K
authors: Siegler
authors: Marion
authors: M
authors: Conn
authors: Bei
authors: B
authors: Shan
authors: Mark P
authors: MP
authors: Grillo
authors: John
authors: J
authors: Eksterowicz
authors: Peter
authors: P
authors: Coward
authors: Jiwen Jim
authors: JJ
authors: Liu
mesh_terms: D000814:Aniline Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D055808:Drug Discovery; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D000814:Aniline Compounds; C519854:GPR119 protein, human; D043562:Receptors, G-Protein-Coupled