Discovery of fused bicyclic agonists of the orphan G-protein coupled receptor GPR119 with in vivo activity in rodent models of glucose control

…, G Pereira, I Calderon, K Choi, Y Xiong, YJ Shin…

Index: Semple, Graeme; Ren, Albert; Fioravanti, Beatriz; Pereira, Guillherme; Calderon, Imelda; Choi, Karoline; Xiong, Yifeng; Shin, Young-Jun; Gharbaoui, Tawfik; Sage, Carleton R.; Morgan, Michael; Xing, Charles; Chu, Zhi-Liang; Leonard, James N.; Grottick, Andrew J.; Al-Shamma, Hussein; Liang, Yin; Demarest, Keith T.; Jones, Robert M. Bioorganic and Medicinal Chemistry Letters, 2011 , vol. 21, # 10 p. 3134 - 3141

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Citation Number: 38

Abstract

Abstract We herein outline the design of a new series of agonists of the pancreatic and GI- expressed orphan G-protein coupled receptor GPR119, a target that has been of significant recent interest in the field of metabolism, starting from our prototypical agonist AR231453. A number of key parameters were improved first by incorporation of a pyrazolopyrimidine core to create a new structural series and secondly by the introduction of a piperidine ether ...