Design, synthesis, and structure-affinity relationship studies in NK1 receptor ligands based on azole-fused quinolinecarboxamide moieties

被引：51
|
作者：
Cappelli, Andrea [1 ,2 ]
Giuliani, Germano [1 ,2 ]
Anzini, Maurizio [1 ,2 ]
Riitano, Daniela [3 ]
Giorgi, Gianluca [4 ]
Vomero, Salvatore [1 ,2 ]
机构：
[1] Univ Siena, Dipartimento Farm Chim Tecnol, I-53100 Siena, Italy
[2] Univ Siena, European Res Ctr Drug Discovery & Dev, I-53100 Siena, Italy
[3] Ist Super Sanita, Dipartimento Farmacol, I-00161 Rome, Italy
[4] Univ Siena, Dipartimento Chim, I-53100 Siena, Italy
来源：
BIOORGANIC & MEDICINAL CHEMISTRY | 2008年 / 16卷 / 14期
关键词：
neurokinin; NK1; receptor; substance P; synthesis; amide derivatives;
D O I：
10.1016/j.bmc.2008.05.067
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
The substituent in position 2 of the quinoline nucleus of NK1 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 NK1 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. (c) 2008 Elsevier Ltd. All rights reserved.
引用
收藏
页码：6850 / 6859
页数：10
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