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 11b–c .