Sahn James J, Hodges Timothy R, Chan Jessica Z, Martin Stephen F
Department of Chemistry, The University of Texas at Austin, Austin, Texas 78712, United States.
ACS Med Chem Lett. 2017 Mar 21;8(4):455-460. doi: 10.1021/acsmedchemlett.7b00066. eCollection 2017 Apr 13.
Some norbenzomorphans exhibit high affinity for sigma 1 and sigma 2 receptors, and varying the position of substituents on the aromatic ring of this scaffold has a significant effect on subtype selectivity. In particular, compounds bearing several different substituents at C7 of the norbenzomorphan ring system exhibit a general preference for the sigma 1 receptor, whereas the corresponding C8-substituted analogues preferentially bind at the sigma 2 receptor. These findings suggest that the norbenzomorphan scaffold may be a unique chemical template that can be easily tuned to prepare small molecules for use as tool compounds to study the specific biological effects arising from preferential binding at either sigma receptor subtype. In the absence of structural characterization data for the sigma 2 receptor, such compounds will be useful toward refining the pharmacophore model of its binding site.
一些去甲苯并吗啡烷对σ1和σ2受体表现出高亲和力，并且改变该骨架芳香环上取代基的位置对亚型选择性有显著影响。特别地，在去甲苯并吗啡烷环系统的C7位带有几个不同取代基的化合物通常对σ1受体有偏好，而相应的C8取代类似物则优先结合于σ2受体。这些发现表明，去甲苯并吗啡烷骨架可能是一种独特的化学模板，可轻松调节以制备小分子用作工具化合物，来研究优先结合任一σ受体亚型所产生的特定生物学效应。在缺乏σ2受体结构表征数据的情况下，此类化合物将有助于完善其结合位点的药效团模型。
