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

页码：6850 / 6859

页数：10

共 22 条

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