鉴定1S,2R-米那普明类似物作为有效的去甲肾上腺素和5-羟色胺转运体抑制剂。

Identification of 1S,2R-milnacipran analogs as potent norepinephrine and serotonin transporter inhibitors.

作者信息

Tamiya Junko, Dyck Brian, Zhang Mingzhu, Phan Kasey, Fleck Beth A, Aparicio Anna, Jovic Florence, Tran Joe A, Vickers Troy, Grey Jonathan, Foster Alan C, Chen Chen

机构信息

Department of Medicinal Chemistry, Neurocrine Bioscience, Inc., 12790 El Camino Real, San Diego, CA 92130, USA.

出版信息

Bioorg Med Chem Lett. 2008 Jun 1;18(11):3328-32. doi: 10.1016/j.bmcl.2008.04.025. Epub 2008 Apr 15.

DOI:10.1016/j.bmcl.2008.04.025

PMID:18445525

Abstract

A series of milnacipran analogs were synthesized and studied as monoamine transporter inhibitors, and several potent compounds with moderate lipophilicity were identified from the 1S,2R-isomers. Thus, 15l exhibited IC(50) values of 1.7nM at NET and 25nM at SERT, which were, respectively, 20- and 13-fold more potent than 1S,2R-milnacipran 1-II.

摘要

合成了一系列米那普明类似物并作为单胺转运体抑制剂进行研究，从1S,2R-异构体中鉴定出了几种具有适度亲脂性的强效化合物。因此，15l对去甲肾上腺素转运体（NET）的IC50值为1.7 nM，对5-羟色胺转运体（SERT）的IC50值为25 nM，其效力分别比1S,2R-米那普明1-II高20倍和13倍。