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 1H-NOESY experiments were a helpful tool for the assignment of the isomeric structures of compounds 9 and llb-c.
Borioni
Anna
A
Dipartimento del Farmaco, Istituto Superiore di Sanità, Roma, Italy. anna.borioni@iss.it
Mustazza
Carlo
C
Sestili
Isabella
I
Sbraccia
Maria
M
Turchetto
Luciana
L
Del Giudice
Maria Rosaria
MR
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
D008024:Ligands; D011804:Quinolines; D018041:Receptors, Neurokinin-2; D018042:Receptors, Neurokinin-3; C106585:SB 218795