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Discovery and optimization of arylsulfonyl 3-(pyridin-2-yloxy)anilines as novel GPR119 agonists |
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| Authors: | Jian 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 Liu |
| Affiliation: | 1. Department of Therapeutic Discovery, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA;2. Department of Metabolic Disorders, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA;3. Department of Pharmacokinetics & Drug Metabolism, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA |
| 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. |
| Keywords: | GPR119 agonist Type 2 diabetes Metabolic stability SAR optimization |
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