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

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...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2013-06, Vol.23 (12), p.3609-3613
Main Authors: Zhang, Jian (Ken), Li, An-Rong, Yu, Ming, Wang, Yingcai, Zhu, Jiang, Kayser, Frank, Medina, Julio C., Siegler, Karen, Conn, Marion, Shan, Bei, Grillo, Mark P., Eksterowicz, John, Coward, Peter, Liu, Jiwen (Jim)
Format: Article
Language:English
Subjects:
agonists
Aniline Compounds - chemical synthesis
Aniline Compounds - chemistry
Aniline Compounds - pharmacology
Animals
chemistry
Diabetes Mellitus, Type 2 - drug therapy
Drug Discovery
GPR119 agonist
Humans
Metabolic stability
Mice
Models, Molecular
pharmacokinetics
Receptors, G-Protein-Coupled - agonists
Receptors, G-Protein-Coupled - chemistry
SAR optimization
Structure-Activity Relationship
Type 2 diabetes
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Summary: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. 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.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2013.04.014