2-Phenyl-4-quinolinecarboxamides:  A Novel Class of Potent and Selective Non-Peptide Competitive Antagonists for the Human Neurokinin-3 Receptor

Pharmacological and molecular biological studies indicate the existence of at least three human tachykinin receptor subtypes, designated neurokinin-1 (NK-1), neurokinin-2 (NK-2), and neurokinin-3 (NK-3), which belong to the superfamily of G-protein-coupled receptors possessing seven transmembrane domains. The endogenous ligands for these receptors constitute a family of small neuropeptides, named tachykinins or neurokinins, which share the common carboxy-terminal region Phe-X-Gly-Leu-MetNH sub(2). The main mammalian tachykinins, substance P, neurokinin A (NKA), and neurokinin B (NKB), interact with all three tachykinin receptors, although there is a defined agonist rank order of potency for NK-1, NK-2, and NK-3 receptors, respectively; for example, for the NK-3 receptor the rank potency order is NKB > NKA > substance P.