The development of a novel series of non-peptide tachykinin NK3 receptor selective antagonists

In this paper we describe the transformation of a series of modified dipeptide NK3 receptor selective ligands, previously developed from a hit identified from the screening of a dipeptide chemical library, into non-peptide, nanomolar affinity NK3 receptor selective antagonists eg. PD160946 and PD161182. PD 161182 blocks senktide-induced human NK3 receptor mediated increases in intracellular calcium levels with a Ke of 0.88nM.