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.
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
Andrea
A
Cappelli
Germano
G
Giuliani
Maurizio
M
Anzini
Daniela
D
Riitano
Gianluca
G
Giorgi
Salvatore
S
Vomero
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