Design, synthesis, and structure-affinity relationship studies in NK1 receptor ligands based on azole-fused quinolinecarboxamide moieties.
The substituent in position 2 of the quinoline nucleus of NK(1) receptor ligands 5 has been constrained into different five-membered heterocyclic moieties in order to obtain information on the binding site pocket interacting with this apparently critical portion of ligands 5. This structure-affinity relationship study led to the discovery of novel tricyclic NK(1) receptor ligands 6 showing affinity in the nanomolar range to the sub-micromolar one. The systematic structure variation suggests that electronic features of the tricyclic moiety play a role in modulating the interaction of these amide derivatives with their receptor.
Cappelli
Andrea
A
Dipartimento Farmaco Chimico Tecnologico and European Research Centre for Drug Discovery and Development, Università degli Studi di Siena, Via A. Moro, 53100 Siena, Italy. cappelli@unisi.it
Giuliani
Germano
G
Anzini
Maurizio
M
Riitano
Daniela
D
Giorgi
Gianluca
G
Vomero
Salvatore
S
D000577:Amides / Q000737:chemistry* / Q000378:metabolism; D001393:Azoles; D001665:Binding Sites; D015195:Drug Design; D006801:Humans; D008024:Ligands; D021281:Quantitative Structure-Activity Relationship; D011804:Quinolines; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*
D000577:Amides; D001393:Azoles; D008024:Ligands; D011804:Quinolines; D018040:Receptors, Neurokinin-1