Identification of spirocyclic piperidine-azetidine inverse agonists of the ghrelin receptor

…, S Cabral, W Jiao, M Fichtner, PA Carpino…

Index: Kung, Daniel W.; Coffey, Steven B.; Jones, Ryan M.; Cabral, Shawn; Jiao, Wenhua; Fichtner, Michael; Carpino, Philip A.; Rose, Colin R.; Hank, Richard F.; Lopaze, Michael G.; Swartz, Roger; Chen, Hou Tommy; Hendsch, Zachary; Posner, Bruce; Wielis, Christopher F.; Manning, Brian; Dubins, Jeffrey; Stock, Ingrid A.; Varma, Sam; Campbell, Mary; Debartola, Demetria; Kosa-Maines, Rachel; Steyn, Stefanus J.; McClure, Kim F. Bioorganic and Medicinal Chemistry Letters, 2012 , vol. 22, # 13 p. 4281 - 4287

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Citation Number: 16

Abstract

The discovery of spirocyclic piperidine-azetidine inverse agonists of the ghrelin receptor is described. The characterization and redressing of the issues associated with these compounds is detailed. An efficient three-step synthesis and a binding assay were relied upon as the primary means of rapidly improving potency and ADMET properties for this class of inverse agonist compounds. Compound 10n bearing distributed polarity in the ...