title: Synthesis of new 4-heteroaryl-2-phenylquinolines and their pharmacological activity as NK-2/NK-3 receptor ligands.
abstract: 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 1H-NOESY experiments were a helpful tool for the assignment of the isomeric structures of compounds 9 and llb-c.
authors.affiliation: Dipartimento del Farmaco, Istituto Superiore di Sanità, Roma, Italy. anna.borioni@iss.it
authors.forename: Anna
authors.initials: A
authors.lastname: Borioni
authors.forename: Carlo
authors.initials: C
authors.lastname: Mustazza
authors.forename: Isabella
authors.initials: I
authors.lastname: Sestili
authors.forename: Maria
authors.initials: M
authors.lastname: Sbraccia
authors.forename: Luciana
authors.initials: L
authors.lastname: Turchetto
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Del Giudice
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D005240:Feasibility Studies; D006801:Humans; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D018041:Receptors, Neurokinin-2 / Q000235:genetics / Q000378:metabolism*; D018042:Receptors, Neurokinin-3 / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014162:Transfection
chemical_list: D008024:Ligands; D011804:Quinolines; D018041:Receptors, Neurokinin-2; D018042:Receptors, Neurokinin-3; C106585:SB 218795