Discovery of a nortropanol derivative as a potent and orally active GPR119 agonist for type 2 diabetes

…, H Vaccaro, XL Xu, H Baker, K O'Neill, M Woods…

文献索引：Xia, Yan; Chackalamannil, Samuel; Greenlee, William J.; Jayne, Charles; Neustadt, Bernard; Stamford, Andrew; Vaccaro, Henry; Xu, Xiaoying; Baker, Hana; O'Neill, Kim; Woods, Morgan; Hawes, Brian; Kowalski, Tim Bioorganic and Medicinal Chemistry Letters, 2011 , vol. 21, # 11 p. 3290 - 3296

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被引用次数: 26

摘要

Abstract The lead optimization studies of a series of GPR119 agonists incorporating a nortropanol scaffold are described. Extensive structure–activity relationship (SAR) studies of the lead compound 20f led to the identification of compound 36j as a potent, single digit nanomolar GPR119 agonist with high agonist activity. Compound 36j was orally active in lowering blood glucose levels in a mouse oral glucose tolerance test and increased ...