α2-adrenoreceptors profile modulation.: 2.: Biphenyline analogues as tools for selective activation of the α2C-subtype

被引：34

作者：

Gentili, F

Ghelfi, F

Giannella, M

Piergentili, A

Pigini, M

Quaglia, W

Vesprini, C

Crassous, PA

Paris, H

Carrieri, A

机构：

[1] Univ Camerino, Dipartimento Sci Chim, I-62032 Camerino, Italy

[2] CHU Rangueil, INSERM, Unit 388, Inst Louis Bugnard,IFR31, F-31403 Toulouse, France

[3] Univ Bari, Dipartimento Farmacochim, I-70125 Bari, Italy

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2004年 / 47卷 / 25期

关键词：

D O I：

10.1021/jm0408215

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of derivatives structurally related to biphenyline (3) was designed with the aim to modulate selectivity toward the alpha(2)-AR subtypes. The results obtained demonstrated that the presence of a correctly oriented function with positive electronic effect (+sigma) in portion X of the ligands is an important factor for significant alpha(2C)-subtype selectivity (imidazolines 5, 13, 16, and 19). Homology modeling and docking studies support experimental data and highlight the crucial role for the hydrogen bond between the pyridine nitrogen in. position 3 of 5 and the NH-indole ring of Trp6.48, which is favorably oriented in the alpha(2C)-subtype, only.

引用

页码：6160 / 6173

页数：14

共 68 条

[1] The alpha-2A-adrenoceptor agonist, guanfacine, increases regional cerebral blood flow in dorsolateral prefrontal cortex of monkeys performing a spatial working memory task [J].