Hydroxy-Substituted Heteroarylpiperazines: Novel Scaffolds for beta-Arrestin-Biased D2R Agonists

Maennel Barbara; Dengler Daniela; Shonberg Jeremy; Huebner Harald; Moeller Dorothee; Gmeiner Peter

首页> 外文期刊>Journal of Medicinal Chemistry >Hydroxy-Substituted Heteroarylpiperazines: Novel Scaffolds for beta-Arrestin-Biased D2R Agonists

【24h】

Hydroxy-Substituted Heteroarylpiperazines: Novel Scaffolds for beta-Arrestin-Biased D2R Agonists

机译：羟基取代的杂芳基哌嗪：用于β-抑制偏置的D2R激动剂的新型支架

获取原文

获取原文并翻译 | 示例

掌桥外文数据库（机构版） >>

开具论文收录证明 >>

文献代查 >>

页面导航

摘要
著录项
相似文献
相关主题

摘要

By means of a formal structural hybridization of the antipsychotic drug aripiprazole and the heterocyclic catecholamine surrogates present in the beta(2)-adrenoceptor agonists procaterol and BI-167107 (4),, we designed and synthesized a collection of novel hydroxy-substituted heteroarylpiperazines and heteroatylhomopiperazines with high dopamine D-2 receptor (D2R) affinity. In contrast to the weak agonistic behavior of aripiprazole, these ligands are capable of effectively mimicking those interactions of dopamine and the. D2R. that are crucial for an active state, leading to the recruitment of beta-arrestin-2. Interestingly, some ligands show considerably lower intrinsic activity in guanine nucleotide exchange experiments at D2R. and consequently represent biased agonists favoring beta-arrestin-2 recruitment over canonical G protein activation. The ligands' agonistic properties are substantially driven by thepresence of an endocyclic H-bond donor.

机译：通过抗精神病药物的正式结构杂交和β（2） - β-胞嘧啶的杂交类丙醇丙氨酸丙醇和BI-167107（4）中存在的杂环儿茶酚胺替代，我们设计并合成了一种新的羟基取代的杂芳基哌嗪和具有高多巴胺D-2受体（D2R）亲和力的杂种原子哌嗪。与阿里普哌唑的弱激动行为相反，这些配体能够有效地模拟多巴胺和该相互作用。 D2R。这对活跃国家至关重要，导致招募β-arrestin-2。有趣的是，一些配体在D2R的鸟嘌呤核苷酸交换实验中显示出相当低的内在活性。因此，代表了偏见的激动剂，青睐β-interniN-2对典型G蛋白激活的招募。配体的激动性质基本上由环环H键供体的假期驱动。

著录项

来源
《Journal of Medicinal Chemistry》 |2017年第11期|共21页
作者
Maennel Barbara; Dengler Daniela; Shonberg Jeremy; Huebner Harald; Moeller Dorothee; Gmeiner Peter;
展开▼
作者单位

Friedrich Alexander Univ Erlangen Nuernberg Dept Chem &

Pharm Med Chem Schuhstr 19 D-91052 Erlangen Germany;

Friedrich Alexander Univ Erlangen Nuernberg Dept Chem &

Pharm Med Chem Schuhstr 19 D-91052 Erlangen Germany;

Friedrich Alexander Univ Erlangen Nuernberg Dept Chem &

Pharm Med Chem Schuhstr 19 D-91052 Erlangen Germany;

Friedrich Alexander Univ Erlangen Nuernberg Dept Chem &

Pharm Med Chem Schuhstr 19 D-91052 Erlangen Germany;

Friedrich Alexander Univ Erlangen Nuernberg Dept Chem &

Pharm Med Chem Schuhstr 19 D-91052 Erlangen Germany;

Friedrich Alexander Univ Erlangen Nuernberg Dept Chem &

Pharm Med Chem Schuhstr 19 D-91052 Erlangen Germany;

展开▼
收录信息
原文格式 PDF
正文语种 eng
中图分类药学;
关键词

相似文献

外文文献
中文文献
专利

1. Hydroxy-Substituted Heteroarylpiperazines: Novel Scaffolds for beta-Arrestin-Biased D2R Agonists [J] . Maennel Barbara, Dengler Daniela, Shonberg Jeremy, Journal of Medicinal Chemistry . 2017,第11期

机译：羟基取代的杂芳基哌嗪：用于β-抑制偏置的D2R激动剂的新型支架
2. The Beta-Arrestin-Biased Dopamine D2 Receptor Ligand, UNC9994, Is a Partial Agonist at G-Protein-Mediated Potassium Channel Activation [J] . ?gren Richard, ?rhem Peter, Nilsson Johanna, The international journal of neuropsychopharmacology . 2018,第12期

机译：Beta-Arrestin导致的多巴胺D2受体配体UNC9994是G蛋白介导的钾通道活化的部分激动剂。
3. Hallucinogenic 5-HT2AR agonists LSD and DOI enhance dopamine D2R protomer recognition and signaling of D2-5-HT2A heteroreceptor complexes [J] . Borroto-EscuelaD.O., Romero-FernandezW., NarvaezM., Biochemical and Biophysical Research Communications . 2014,第1期

机译：致幻剂5-HT2AR激动剂LSD和DOI增强了多巴胺D2R前体的识别和D2-5-HT2A异源受体复合物的信号传导
4. Pan-PPAR Agonists Based on the Resveratrol Scaffold: Biological Evaluation and Docking Studies [C] . Wei Li, Xinhua He, Weiguo Shi, International conference of molecular simulations and applied informatics technologies . 2012

机译：基于白藜芦醇支架的Pan-PPAR激动剂：生物学评估和对接研究
5. Tetrapeptide Melanocortin Agonist Ligands Exploring Selectivity of the mMC3R Using DPhe Substitutions in the Ac-His-Arg-DPhe-Tic-NH2 Scaffold [D] . Schlasner, Katherine N. 2018

机译：四肽Melanocortin激动剂配体在AC-HIS-ARG-DPHE-NH2支架中使用DPHE取代探索MMC3R的选择性
6. The Beta-Arrestin-Biased Dopamine D2 Receptor Ligand UNC9994 Is a Partial Agonist at G-Protein-Mediated Potassium Channel Activation [O] . Richard Ågren, Peter Århem, Johanna Nilsson, 2018

机译：Beta-Arrestin偏爱的多巴胺D2受体配体UNC9994是G蛋白介导的钾通道活化的部分激动剂。
7. Dopamine D2 receptor-mediated modulation of adenosine A2A receptor agonist binding within the A2AR/D2R oligomer framework [O] . Víctor Fernández-Dueñas, Maricel Gómez-Soler, Xavier Morató, 2013

机译：多巴胺D2受体介导的A2AR / D2R低聚物框架内的腺苷A2A受体激动剂结合的调节

Hydroxy-Substituted Heteroarylpiperazines: Novel Scaffolds for beta-Arrestin-Biased D2R Agonists

摘要

著录项

相似文献

相关主题

期刊订阅