Discovery and optimization of arylsulfonyl 3-(pyridin-2-yloxy)anilines as novel GPR119 agonists

Jian Ken Zhang; An-Rong Li; Ming Yu; Yingcai Wang; Jiang Zhu; Frank Kayser; Julio C Medina; Karen Siegler; Marion Conn; Bei Shan; Mark P Grillo; John Eksterowicz; Peter Coward; Jiwen Jim Liu

doi:10.1016/j.bmcl.2013.04.014

Discovery and optimization of arylsulfonyl 3-(pyridin-2-yloxy)anilines as novel GPR119 agonists

Bioorg Med Chem Lett. 2013 Jun 15;23(12):3609-13. doi: 10.1016/j.bmcl.2013.04.014. Epub 2013 Apr 15.

Authors

Jian Ken Zhang¹, An-Rong Li, Ming Yu, Yingcai Wang, Jiang Zhu, Frank Kayser, Julio C Medina, Karen Siegler, Marion Conn, Bei Shan, Mark P Grillo, John Eksterowicz, Peter Coward, Jiwen Jim Liu

Affiliation

¹ Department of Therapeutic Discovery, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA. jian@amgen.com

PMID: 23648181
DOI: 10.1016/j.bmcl.2013.04.014

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.

Publication types

Letter

MeSH terms

Aniline Compounds / chemical synthesis
Aniline Compounds / chemistry*
Aniline Compounds / pharmacology*
Animals
Diabetes Mellitus, Type 2 / drug therapy
Drug Discovery
Humans
Mice
Models, Molecular
Receptors, G-Protein-Coupled / agonists*
Receptors, G-Protein-Coupled / chemistry
Structure-Activity Relationship

Substances

Aniline Compounds
GPR119 protein, human
Receptors, G-Protein-Coupled