1-(3-(biphenyl-4-yl)butyl)piperidine | 1346216-60-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-(3-(biphenyl-4-yl)butyl)piperidine
• 英文别名: 1-[3-(4-Phenylphenyl)butyl]piperidine
• CAS: 1346216-60-1
• 化学式: C₂₁H₂₇N
• 分子量: 293.452
• InChiKey: BJQAKTZCQPXMQT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  3.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1-(3-(biphenyl-4-yl)butyl)piperidine 在 盐酸 作用下， 以 甲醇 、 水 为溶剂， 以2.53 g的产率得到1-(3-(biphenyl-4-yl)butyl)piperidine hydrochloride
  参考文献：
  名称：

  RC-33是增强PC12细胞中NGF诱导的神经突增生的有效和选择性σ1受体激动剂。第2部分：g级合成，理化特性和体外代谢稳定性

  摘要：

  有力的药理证据表明，σ1受体与所有主要中枢神经系统疾病的病理生理有关。在过去的几年我们的研究小组进行了旨在发现新σ1配体的深入研究，我们最近选择（[R /小号）- RC-33作为一种新型强效的选择性σ1受体激动剂。作为我们在这一领域工作的继续，在这里我们报告了我们在开发这种新的σ1受体激动剂方面所做的努力。最初，我们通过计算机模拟研究了RC-33的（R）和（S）对映异构体与σ1受体的结合。（R）-RC-33和（S）-RC-33蛋白证明RC-33与σ1受体非立体选择性结合；反过来，这支持了消旋形式的RC-33的进一步开发和表征。随后，我们建立一个按比例放大的，优化的（合成- [R /小号）- RC-33的一些化合物的表征数据一起（例如，在不同的介质并通过热分析技术固态表征溶解度）。最后，在不同物种（例如大鼠，小鼠，狗和人）的不同生物基质（例如血浆，血液和肝S9部分）中进行了RC-33的代谢研究。（R

  DOI：

  10.1016/j.bmc.2013.02.029
• 作为产物：
  描述：

  β-Methyl<1,1'-biphenyl>-4-propansaeure 在 lithium aluminium tetrahydride 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 作用下， 以 四氢呋喃 为溶剂， 反应 3.41h， 生成 1-(3-(biphenyl-4-yl)butyl)piperidine
  参考文献：
  名称：

  RC-33对映体作为神经保护剂的研究：分离，构型分配和初步生物学概况。

  摘要：

  在这项研究中，我们探讨了手性在RC-33的生物活性中的作用，最近我们以消旋形式对其进行了研究。不对称合成程序是第一个实验，导致所需的对映体富集的RC-33，但对映体过量（ee）不足以支持体外研究。然后成功进行了对映选择性高效液相色谱（HPLC）程序，得到的RC-33对映异构体的数量和光学纯度均适合药理学研究。利用先前设计的不对称合成，很容易分配纯对映异构体的绝对构型。正如在体外生物学初步研究中发现的那样，（小号） -和（R）-RC-33具有相当的亲和力朝向σ 1受体和非常在钙流入测定中的相似行为，从而产生同等有效的σ 1受体激动剂。总的来说，到目前为止获得的结果表明与生物靶标的相互作用是非立体选择性的，并且使我们假设RC-33的生物活性中缺乏立体选择性。手性25：814–822，2013年。©2013 Wiley Periodicals，Inc.

  DOI：

  10.1002/chir.22223

文献信息

• Sigma-1 Receptor Agonists Acting on Aquaporin-Mediated H2O2 Permeability: New Tools for Counteracting Oxidative Stress
  作者：Giorgia Pellavio、Giacomo Rossino、Giulia Gastaldi、Daniela Rossi、Pasquale Linciano、Simona Collina、Umberto Laforenza

  DOI：10.3390/ijms22189790

  日期：——

  Sigma1 Receptor (S1R) is involved in oxidative stress, since its activation is triggered by oxidative or endoplasmic reticulum stress. Since specific aquaporins (AQP), called peroxiporins, play a relevant role in controlling H2O2 permeability and ensure reactive oxygen species wasted during oxidative stress, we studied the effect of S1R modulators on AQP-dependent water and hydrogen peroxide permeability in the presence and in the absence of oxidative stress. Applying stopped-flow light scattering and fluorescent probe methods, water and hydrogen peroxide permeability in HeLa cells have been studied. Results evidenced that S1R agonists can restore water permeability in heat-stressed cells and the co-administration with a S1R antagonist totally counteracted the ability to restore the water permeability. Moreover, compounds were able to counteract the oxidative stress of HeLa cells specifically knocked down for S1R. Taken together these results support the hypothesis that the antioxidant mechanism is mediated by both S1R and AQP-mediated H2O2 permeability. The finding that small molecules can act on both S1R and AQP-mediated H2O2 permeability opens a new direction toward the identification of innovative drugs able to regulate cell survival during oxidative stress in pathologic conditions, such as cancer and degenerative diseases.

  Sigma1受体（S1R）参与氧化应激，因为其激活是由氧化或内质网应激触发的。由于特定的水通道蛋白（AQP），被称为过氧化物通道蛋白，在控制H2O2渗透性和确保在氧化应激期间废弃的活性氧物质方面发挥了重要作用，我们研究了S1R调节剂对AQP依赖性水和过氧化氢渗透性在有氧化应激和无氧化应激条件下的影响。通过应用停流光散射和荧光探针方法，研究了HeLa细胞中的水和过氧化氢渗透性。结果表明，S1R激动剂可以恢复受热应激细胞的水渗透性，而与S1R拮抗剂联合给药完全抵消了恢复水渗透性的能力。此外，化合物能够抵消对S1R特异敲除的HeLa细胞的氧化应激。综合这些结果支持抗氧化机制是通过S1R和AQP介导的 渗透性来介导的假说。发现小分子可以作用于S1R和AQP介导的 渗透性，开辟了一条新的方向，以便鉴定能够在病理条件下，如癌症和退行性疾病中调节细胞存活的创新药物。
• Use of Sigma-1 receptor agonist compounds
  申请人：MTA TÁMOGATOTT KUTATÓCSOPORTOK IRODÁJA

  公开号：US10842794B2

  公开（公告）日：2020-11-24

  Compositions and methods for the prevention, inhibition, and/or treatment of progressive fibrosis present in various fibroproliferative disorders. Embodiments relate to the use of Sigma-1 receptor agonists for use in the treatment of prevention of progressive fibrosis characterized by the over proliferation of ECM producing cells, e.g. myofibroblasts and by the excessive deposition of ECM components in a medical or disease condition. Preferred Sigma-1 agonists are disclosed.

  用于预防、抑制和/或治疗各种纤维增生性疾病中出现的进行性纤维化的组合物和方法。本发明的实施方案涉及 Sigma-1 受体激动剂在治疗和预防进行性纤维化方面的用途，进行性纤维化的特征是产生 ECM 的细胞（如肌成纤维细胞）过度增殖，以及医疗或疾病条件下 ECM 成分的过度沉积。本文公开了优选的 Sigma-1 激动剂。
• Identification of a potent and selective σ1 receptor agonist potentiating NGF-induced neurite outgrowth in PC12 cells
  作者：Daniela Rossi、Alice Pedrali、Mariangela Urbano、Raffaella Gaggeri、Massimo Serra、Leyden Fernández、Michael Fernández、Julio Caballero、Simone Ronsisvalle、Orazio Prezzavento、Dirk Schepmann、Bernhard Wuensch、Marco Peviani、Daniela Curti、Ornella Azzolina、Simona Collina

  DOI：10.1016/j.bmc.2011.09.016

  日期：2011.11

  Herein we report the synthesis, drug-likeness evaluation, and in vitro studies of new sigma (sigma) ligands based on arylalkenylaminic scaffold. For the most active olefin the corresponding arylalkylamine was studied. Novel arylalkenylamines generally possess high sigma(1) receptor affinity (K-i values <25 nM) and good sigma(1)/sigma(2) selectivity (K-i sigma(2) > 100). Particularly, the piperidine derivative (E)-17 and its arylalkylamine analog (R, S)-33 were observed to be excellent sigma(1) receptor ligands (K-i = 0.70 and 0.86 nM, respectively) and to display significantly high selectivity over sigma(2), mu-, and kappa-opioid receptors and phencyclidine (PCP) binding site of the N-methyl-D-aspartate (NMDA) receptors. Moreover in PC12 cells (R, S)-33 promoted the nerve growth factor (NGF)-induced neurite outgrowth and elongation. Co-administration of the selective sigma(1) receptor antagonist BD-1063 totally counteracted this effect, confirming that sigma(1) receptors are involved in the (R,S)-33 modulation of the NGF effect in PC12 cells and suggesting a sigma(1) agonist profile. As a part of our work, a threedimensional sigma(1) pharmacophore model was also developed employing GALAHAD methodology. Only active compounds were used for deriving this model. The model included two hydrophobes and a positive nitrogen as relevant features and it was able to discriminate between molecules with and without affinity toward sigma(1) receptor subtype. (C) 2011 Elsevier Ltd. All rights reserved.
• NOVEL USE OF SIGMA-1 RECEPTOR AGONIST COMPOUNDS
  申请人：MTA TÁMOGATOTT KUTATÓCSOPORTOK IRODÁJA

  公开号：US20160346290A1

  公开（公告）日：2016-12-01

  The present invention is directed to compositions and methods for the prevention, inhibition, and/or treatment of progressive fibrosis present in various fibroproliferative disorders. In particular, embodiments of the present invention relate to the use of Sigma-1 receptor agonists for use in the treatment or prevention of progressive fibrosis characterized by the overproliferation of ECM producing cells, e.g. myofibroblasts and by the excessive deposition of ECM components in a medical or disease condition. Preferred Sigma-1-receptor agonists are disclosed.
• US4110447A
  申请人：——

  公开号：US4110447A

  公开（公告）日：1978-08-29