Discovery of dopamine D4 receptor antagonists with planar chirality

被引：7

作者：

Sanna, Fabrizio ^{[1
]}

Ortner, Birgit ^{[1
]}

Huebner, Harald ^{[1
]}

Loeber, Stefan ^{[1
]}

Tschammer, Nuska ^{[1
]}

Gmeiner, Peter ^{[1
]}

机构：

[1] Univ Erlangen Nurnberg, Dept Med Chem, Emil Fischer Ctr, D-91052 Erlangen, Germany

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2013年 / 21卷 / 07期

关键词：

GPCR; Dopamine; Subtype selectivity; Ligand efficacy; Paracyclophane; Planar chirality; PENILE ERECTION; PARTIAL AGONISTS; HIGH-AFFINITY; CYCLIC-AMP; CELL-LINE; BINDING; LIGANDS; DERIVATIVES; SUBTYPE; BIOISOSTERES;

D O I：

10.1016/j.bmc.2013.01.065

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：

Employing the D-4 selective phenylpiperazine 2 as a lead compound, planar chiral analogs with paracyclophane substructure were synthesized and evaluated for their ability to bind and activate dopamine receptors. The study revealed that the introduction of a [2.2]paracyclophane moiety is tolerated by dopamine receptors of the D-2 family. Subtype selectivity for D-4 and ligand efficacy depend on the absolute configuration of the test compounds. Whereas the achiral single-layered lead 2 and the double-layered paracyclophane (R)-3 showed partial agonist properties, the enantiomer (S)-3 behaved as a neutral antagonist. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：1680 / 1684

页数：5

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