Synthesis, binding affinity and SAR of new benzolactam derivatives as dopamine D3 receptor ligands

被引：31

作者：

Ortega, Raquel ^{[1
]}

Ravina, Enrique ^{[1
]}

Masaguer, Christian F. ^{[1
]}

Areias, Filipe ^{[2
]}

Brea, Jose ^{[2
]}

Loza, Maria I. ^{[2
]}

Lopez, Laura ^{[3
]}

Selent, Jana ^{[3
]}

Pastor, Manuel ^{[3
]}

Sanz, Ferran ^{[3
]}

机构：

[1] Univ Santiago Compostela, Fac Farm, Dept Quim Organ, E-15782 Santiago De Compostela, Spain

[2] Univ Santiago Compostela, Fac Farm, Dept Farmacol, E-15782 Santiago De Compostela, Spain

[3] Univ Pompeu Fabra, IMIM, Res Unit Biomed Informat GRIB, E-08003 Barcelona, Spain

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 06期

关键词：

Dopamine receptors; Antipsychotics; Structure-activity relationship; Benzolactams; Arylpiperazines; SCHMIDT REACTION; SCHIZOPHRENIA; SELECTIVITY; ANTAGONISTS; INHIBITION; MODELS; DRUGS; 2ND;

D O I：

10.1016/j.bmcl.2009.01.067

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of new benzolactam derivatives was synthesized and the derivatives were evaluated for their affinities at the dopamine D-1, D-2, and D-3 receptors. Some of these compounds showed high D-2 and/or D-3 affinity and selectivity over the D-1 receptor. The SAR study of these compounds revealed structural characteristics that decisively influenced their D-2 and D-3 affinities. Structural models of the complexes between some of the most representative compounds of this series and the D-2 and D-3 receptors were obtained with the aim of rationalizing the observed experimental results. Moreover, selected compounds showed moderate binding affinity on 5-HT2A which could contribute to reducing the occurrence of extrapyramidal side effects as potential antipsychotics. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：1773 / 1778

页数：6

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