Discovery of potent, balanced and orally active dual NK1/NK3 receptor ligands.

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.