对一系列含有杂芳基的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的研究。

Studies on a series of milnacipran analogs containing a heteroaromatic group as potent norepinephrine and serotonin transporter inhibitors.

作者信息

Vickers Troy, Dyck Brian, Tamiya Junko, Zhang Mingzhu, Jovic Florence, Grey Jonathan, Fleck Beth A, Aparicio Anna, Johns Michael, Jin Liping, Tang Hui, 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):3230-5. doi: 10.1016/j.bmcl.2008.04.045. Epub 2008 Apr 25.

DOI:10.1016/j.bmcl.2008.04.045

PMID:18468895

Abstract

A series of milnacipran analogs containing a heteroaromatic group were synthesized and studied as monoamine transporter inhibitors. Many compounds exhibited higher potency than milnacipran at NET and NET/SERT with no significant change in lipophilicity. For example, compound R-26f was about 10-fold more potent than milnacipran with IC(50) values of 8.7 and 26nM at NET and SERT, respectively.

摘要

合成了一系列含有杂芳基的米那普明类似物，并将其作为单胺转运体抑制剂进行研究。许多化合物在去甲肾上腺素转运体（NET）和去甲肾上腺素/5-羟色胺转运体（NET/SERT）上表现出比米那普明更高的效力，且亲脂性无显著变化。例如，化合物R-26f的效力比米那普明高约10倍，在NET和SERT上的半数抑制浓度（IC50）值分别为8.7和26 nM。