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Synthesis of New 4‐Heteroaryl‐2‐Phenylquinolines and Their Pharmacological Activity as NK‐2/NK‐3 Receptor Ligands
Author(s) -
Borioni Anna,
Mustazza Carlo,
Sestili Isabella,
Sbraccia Maria,
Turchetto Luciana,
Del Giudice Maria Rosaria
Publication year - 2007
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.200600113
Subject(s) - chemistry , stereochemistry , selectivity , molecule , receptor , ring (chemistry) , acceptor , two dimensional nuclear magnetic resonance spectroscopy , biological activity , combinatorial chemistry , in vitro , catalysis , biochemistry , organic chemistry , physics , condensed matter physics
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 .