Synthesis of New 4-Heteroaryl-2-Phenylquinolines and Their Pharmacological Activity as NK-2/NK-3 Receptor Ligands

Substituted 4-heteroaryl-2-phenylquinolines were synthesized and tested on NK-2 and NK-3 receptors in order to get a better insight in the structure-activity relationship. On the whole, these molecules, which can be regarded as bioisosters of the NK-3 antagonist SB 218795, displayed a lower activity than the template. Ring electronic distribution and H-bond donor and acceptor positions played some role in selectivity, 2-imidazolyl substituted 2a showing affinity mainly towards NK-3 while 3-pyrazolyl substituted 4 displayed a preferential interaction with NK-2 receptor. Structural characterization of the synthesized compounds was achieved by NMR and mass techniques. Bidimensional 1 H-NOESY experiments were a helpful tool for the assignment of the isomeric structures of compounds 9 and llb-c.