用于基于正电子发射断层扫描（PET）的去甲肾上腺素转运体研究的新型化合物的合成及计算机模拟评估

Synthesis and in silico evaluation of novel compounds for PET-based investigations of the norepinephrine transporter.

作者信息

Neudorfer Catharina, Seddik Amir, Shanab Karem, Jurik Andreas, Rami-Mark Christina, Holzer Wolfgang, Ecker Gerhard, Mitterhauser Markus, Wadsak Wolfgang, Spreitzer Helmut

机构信息

Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.

Division of Drug Design and Medicinal Chemistry, Department of Pharmaceutical Chemistry, Faculty of Life Sciences, University of Vienna, Althanstraße 14, 1090 Vienna, Austria.

出版信息

Molecules. 2015 Jan 20;20(1):1712-30. doi: 10.3390/molecules20011712.

DOI:10.3390/molecules20011712

PMID:25608857

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6272146/

Abstract

Since the norepinephrine transporter (NET) is involved in a variety of diseases, the investigation of underlying dysregulation-mechanisms of the norepinephrine (NE) system is of major interest. Based on the previously described highly potent and selective NET ligand 1-(3-(methylamino)-1-phenylpropyl)-3-phenyl-1,3-dihydro-2H-benzimidaz- ol-2-one (Me@APPI), this paper aims at the development of several fluorinated methylamine-based analogs of this compound. The newly synthesized compounds were computationally evaluated for their interactions with the monoamine transporters and represent reference compounds for PET-based investigation of the NET.

摘要

由于去甲肾上腺素转运体（NET）与多种疾病相关，因此对去甲肾上腺素（NE）系统潜在的失调机制进行研究具有重要意义。基于先前描述的高效、选择性NET配体1-(3-(甲氨基)-1-苯基丙基)-3-苯基-1,3-二氢-2H-苯并咪唑-2-酮（Me@APPI），本文旨在开发该化合物的几种基于氟化甲胺的类似物。对新合成的化合物与单胺转运体的相互作用进行了计算评估，它们是基于正电子发射断层扫描（PET）对NET进行研究的参考化合物。