Department of Chemistry & Pharmaceutical Sciences, Piazzale Europa 1, University of Trieste, 34127 Trieste, Italy.
Molecular Simulation Engineering (MOSE) Laboratory, DI3, Piazzale Europa 1, University of Trieste, 34127 Trieste, Italy.
Eur J Med Chem. 2015 Jan 27;90:797-808. doi: 10.1016/j.ejmech.2014.12.018. Epub 2014 Dec 12.
We report the design, synthesis and binding evaluation against σ1 and σ2 receptors of a series of new piperidine-4-carboxamide derivatives variously substituted on the amide nitrogen atom. Specifically, we assessed the effects exerted on σ receptor affinity by substituting the N-benzylcarboxamide group present on a series of compounds previously synthesized in our laboratory with different cyclic or linear moieties. The synthesized compounds 2a-o were tested to estimate their affinity and selectivity toward σ1 and σ2 receptors. Very high σ1 affinity (Ki = 3.7 nM) and Kiσ2/Kiσ1 selectivity ratio (351) were found for the tetrahydroquinoline derivative 2k, featuring a 4-chlorobenzyl moiety linked to the piperidine nitrogen atom.
我们报告了一系列新的哌啶-4-甲酰胺衍生物的设计、合成和对 σ1 和 σ2 受体的结合评估，这些衍生物在酰胺氮原子上有不同的取代。具体来说，我们评估了用不同的环状或线状部分取代我们实验室以前合成的一系列化合物中存在的 N-苄基甲酰胺基团对 σ 受体亲和力的影响。合成的化合物 2a-o 被测试以估计它们对 σ1 和 σ2 受体的亲和力和选择性。具有与哌啶氮原子相连的 4-氯苄基部分的四氢喹啉衍生物 2k 表现出非常高的 σ1 亲和力（Ki = 3.7 nM）和 Kiσ2/Kiσ1 选择性比值（351）。
