Identification of spirocyclic piperidine-azetidine inverse agonists of the ghrelin receptor
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Published on: March 21, 2017
Daniel W Kung1, Steven B Coffey, Ryan M Jones
1Pfizer Worldwide Research and Development, Eastern Point Road, Groton, CT 06340, USA. daniel.w.kung@pfizer.com
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 10 n bearing distributed polarity in the form of an imidazo-thiazole acetamide and a phenyl triazole is a unit lower in logP and has significantly improved binding affinity compared to the hit molecule 10a, providing support for further optimization of this series of compounds.
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