Cao Jianjing, Kopajtic Theresa, Katz Jonathan L, Newman Amy Hauck
Medicinal Chemistry Section, National Institute on Drug Abuse-Intramural Research Program, National Institutes of Health, 333 Cassell Drive, Baltimore, MD 21224, USA.
Bioorg Med Chem Lett. 2008 Oct 1;18(19):5238-41. doi: 10.1016/j.bmcl.2008.08.065. Epub 2008 Aug 22.
Ester analogs of (+/-)3-(4-(3-(bis(4-fluorophenyl)amino)propyl)piperazin-1-yl)-1-phenylpropan-1-ol were synthesized and evaluated for binding at DAT, SERT, NET, and sigma1 receptors, and compared to GBR 12909 and several known sigma1 receptor ligands. Most of these compounds demonstrated high affinity (K(i)=4.3-51 nM) and selectivity for the DAT among the monoamine transporters. S- and R-1-(4-(3-(bis(4-fluorophenyl)amino)propyl)piperazin-1-yl)-3-phenylpropan-2-ol were also prepared wherein modest enantioselectivity was demonstrated at the DAT. However, no enantioselectivity at sigma1 receptors was observed and most of the ester analogs of the more active S-enantiomer showed comparable binding affinities at both DAT and sigma1 receptors with a maximal 16-fold DAT/sigma1 selectivity.
合成了(±)3-(4-(3-(双(4-氟苯基)氨基)丙基)哌嗪-1-基)-1-苯基丙-1-醇的酯类似物，并评估了它们与多巴胺转运体（DAT）、5-羟色胺转运体（SERT）、去甲肾上腺素转运体（NET）和σ1受体的结合情况，并与GBR 12909和几种已知的σ1受体配体进行了比较。这些化合物中的大多数对单胺转运体中的DAT表现出高亲和力（K(i)=4.3 - 51 nM）和选择性。还制备了S-和R-1-(4-(3-(双(4-氟苯基)氨基)丙基)哌嗪-1-基)-3-苯基丙-2-醇，其中在DAT上表现出适度的对映选择性。然而，在σ1受体上未观察到对映选择性，并且活性较高的S-对映体的大多数酯类似物在DAT和σ1受体上均显示出相当的结合亲和力，最大DAT/σ1选择性为16倍。
