Document Report Card

ID: ALA1764954

Journal: J Med Chem

Title: Activation of the G-protein-coupled receptor 119: a conformation-based hypothesis for understanding agonist response.

Authors: McClure KF, Darout E, Guimarães CR, DeNinno MP, Mascitti V, Munchhof MJ, Robinson RP, Kohrt J, Harris AR, Moore DE, Li B, Samp L, Lefker BA, Futatsugi K, Kung D, Bonin PD, Cornelius P, Wang R, Salter E, Hornby S, Kalgutkar AS, Chen Y.

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.

CiteXplore: 21361292

DOI: 10.1021/jm200003p