Activation of the G-Protein-Coupled Receptor 119: A Conformation-Based Hypothesis for Understanding Agonist Response
Journal of Medicinal Chemistry2011Vol. 54(6), pp. 1948–1952
Citations Over TimeTop 10% of 2011 papers
Kim F. McClure, Etzer Darout, Cristiano R. W. Guimarães, Michael P. DeNinno, Vincent Mascitti, Michael J. Munchhof, Ralph P. Robinson, Jeffrey T. Kohrt, Anthony R. Harris, Dianna E. Moore, Bryan Li, Lacey Samp, Bruce A. Lefker, Kentaro Futatsugi, Daniel W. Kung, Paul D. Bonin, Peter Cornelius, Ruduan Wang, E.D. Salter, Sam Hornby, Amit S. Kalgutkar, Yue Chen
Abstract
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.
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