Activation of the G-Protein-Coupled Receptor 119: A Conformation-Based Hypothesis for Understanding Agonist Response
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- 作者：Kim F. McClure ; Etzer Darout ; Cristiano R. W. Guimar茫es ; Michael P. DeNinno ; Vincent Mascitti ; Michael J. Munchhof ; Ralph P. Robinson ; Jeffrey Kohrt ; Anthony R. Harris ; Dianna E. Moore ; Bryan Li ; Lacey Samp ; Bruce A. Lefker ; Kentaro Futatsugi ; Daniel Kung ; Paul D. Bonin ; Peter Cornelius ; Ruduan Wang ; Eben Salter ; Sam Hornby ; Amit S. Kalgutkar ; Yue Chen
- 刊名：Journal of Medicinal Chemistry
- 出版年：2011
- 出版时间：March 24, 2011
- 年：2011
- 卷：54
- 期：6
- 页码：1948-1952
- 全文大小：778K
- 年卷期：v.54,no.6(March 24, 2011)
- ISSN：1520-4804
文摘
The synthesis and properties of the bridged piperidine (oxaazabicyclo) compounds 8, 9, and 11 are described. A conformational analysis of these structures is compared with the representative GPR119 ligand 1. These results and the differences in agonist pharmacology are used to formulate a conformation-based hypothesis to understand activation of the GPR119 receptor. We also show for these structures that the agonist pharmacology in rat masks the important differences in human pharmacology.