(E)-N,N-dimethyl-3-phenylbut-2-en-1-amine hydrochloride | 1346016-21-4

• 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: (E)-N,N-dimethyl-3-phenylbut-2-en-1-amine hydrochloride
• 英文别名: (E)-N,N-dimethyl-3-phenylbut-2-en-1-amine;hydrochloride
• CAS: 1346016-21-4
• 化学式: C₁₂H₁₇N*ClH
• 分子量: 211.735
• InChiKey: KXDDAMDRHVLTOL-LBEJWNQZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.07
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  3.2
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为产物：
  描述：

  溴苯 、 4-(二甲氨基)-2-丁酮 在 叔丁基锂 、 盐酸 作用下， 以 乙醚 、 正戊烷 、 水 为溶剂， 以39%的产率得到(E)-N,N-dimethyl-3-phenylbut-2-en-1-amine hydrochloride
  参考文献：
  名称：

  Identification of a potent and selective σ1 receptor agonist potentiating NGF-induced neurite outgrowth in PC12 cells

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2011.09.016

文献信息

• Gaining in pan-affinity towards sigma 1 and sigma 2 receptors. SAR studies on arylalkylamines
  作者：Daniela Rossi、Marta Rui、Marcello Di Giacomo、Dirk Schepmann、Bernhard Wünsch、Stefania Monteleone、Klaus R. Liedl、Simona Collina

  DOI：10.1016/j.bmc.2016.10.005

  日期：2017.1

  Sigma Receptor (SR) modulators are involved in different signal transduction pathways, representing important pharmacological/therapeutic tools in several pathological conditions, such as neurodegenerative diseases and cancers. To this purpose, numerous compounds have been developed in order to target selectively one of the two subtypes (S1R and S2R) as chemotherapeutic agent. However, experiments have also shown that ligands which are able to bind both SR subtypes can be useful for the diagnosis and/or the treatment of cancers. Therefore, the discovery of compounds with good affinity towards both S1R and S2R ('pan-modulators') is also of great interest and still represents a challenge up to now. For this reason, we synthesized novel arylalkylamines with the aim to obtain compounds with S1R and S2R affinity in the nM range and, by modeling quantitative structure-activity relationships (QSARs), we identified the essential structural features to obtain promising pan-compounds. (C) 2016 Elsevier Ltd. All rights reserved.
• 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.