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A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
Published on: February 20, 2018
Discovery of potent, balanced and orally active dual NK1/NK3 receptor ligands
Jens-Uwe Peters1, Torsten Hoffmann, Patrick Schnider
1F. Hoffmann-La Roche Ltd, Pharma Research, CH-4070 Basel, Switzerland. jens-uwe.peters@roche.com
Abstract:
During a program directed at selective NK(1) receptor antagonists, we serendipitously discovered an NK(1) receptor ligand with additional affinity for the NK(3) receptor. Recognising an opportunity for a drug discovery program aiming for dual NK(1)/NK(3) receptor antagonists, we prepared a series of analogues from a novel, versatile building block. From this series emerged compounds with high and balanced affinities for the NK(1) and the NK(3) receptors. Typical representatives of this series were active in the gerbil foot tapping assay after oral administration.
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