Synthesis and binding profile of haloperidol-based bivalent ligands targeting dopamine D(2)-like receptors.
Synthesis and binding profile of haloperidol-based bivalent ligands targeting dopamine D(2)-like receptors.
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基于氟哌啶醇的二价配体靶向多巴胺 D(2) 样受体的合成和结合概况
DOI：
10.1016/j.bmcl.2014.06.079
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发表时间：
2014
影响因子：
2.7
通讯作者：
P. Gmeiner
中科院分区：
文献类型：
--
作者：
I. Salama;S. Loeber;H. Huebner;P. Gmeiner
多巴胺D2样受体的同源二聚体在精神分裂症的病理生理学中具有特别重要的作用，因此有望成为发现非典型抗精神病药物的靶点。这项研究描述了一系列具有来自多巴胺受体拮抗剂氟哌啶醇的药效团的新型二价分子的开发。研究了这些二聚体与它们的单体类似物的D2long、D2Short、D3和D4受体结合以及连接两个相邻受体原构体的能力。对于含有22个间隔原子的二价配体13，当Hill斜率接近2时，放射性配体结合研究提供了诊断性见解，与单价对照配体的比较分析表明，二价结合模式同时占据两个相邻的结合位点。
Homodimers of dopamine D2-like receptors are suggested to be of particular importance in the pathophysiology of schizophrenia and, thus, serve as promising targets for the discovery of atypical antipsychotics. This study describes the development of a series of novel bivalent molecules with a pharmacophore derived from the dopamine receptor antagonist haloperidol. These dimers were investigated in comparison to their monomeric analogues for their D2long, D2short, D3, and D4receptor binding and the ability to bridge two neighboring receptor protomers. Radioligand binding studies provided diagnostic insights when Hill slopes close to two for the bivalent ligand13incorporating 22 spacer atoms and a comparative analysis with monovalent control ligands indicated a bivalent binding mode with a simultaneous occupancy of two neighboring binding sites.
开发二价多巴胺 D2 受体激动剂。
影响因子：
7.3
作者：
Julia Kühhorn;Angela Götz;H. Hübner;Dawn Thompson;Jennifer L. Whistler;P. Gmeiner
通讯作者：
P. Gmeiner
影响因子：
3.6
作者：
Wang M;Pei L;Fletcher PJ;Kapur S;Seeman P;Liu F
通讯作者：
Liu F
影响因子：
7.3
作者：
Zhang Y;Gilliam A;Maitra R;Damaj MI;Tajuba JM;Seltzman HH;Thomas BF
通讯作者：
Thomas BF