(R)-1-(diphenylmethyl)-4-(2,3-epoxypropyl)piperazine | 165657-99-8

• 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: (R)-1-(diphenylmethyl)-4-(2,3-epoxypropyl)piperazine
• 英文别名: 1-benzhydryl-4-((R)-1-oxiranylmethyl)-piperazine；1-benzhydryl-4-[[(2R)-oxiran-2-yl]methyl]piperazine
• CAS: 165657-99-8
• 化学式: C₂₀H₂₄N₂O
• 分子量: 308.423
• InChiKey: PNBNIKKSFYNIFB-LJQANCHMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  19
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (R)-1-(diphenylmethyl)-4-(2,3-epoxypropyl)piperazine 、 环丙基甲胺 以 乙醇 为溶剂， 反应 6.0h， 生成 (S)-1-(4-benzhydryl-piperazin-1-yl)-3-((cyclopropylmethyl)-amino)-propan-2-ol
  参考文献：
  名称：

  BACE1 inhibitory activities of enantiomerically pure, variously substituted N-(3-(4-benzhydrylpiperazin-1-yl)-2-hydroxypropyl) arylsulfonamides

  摘要：

  beta-Secretase (BACE1) has been widely recognized as one of the possible therapeutic targets for the treatment of Alzheimer's disease. In this paper, we report the synthesis and the BACE1 inhibitory activity of new, variously substituted N-(3-(4-benzhydrylpiperazin-1-yl)-2-hydroxypropyl) arylsulfonamides. Each enantiomeric form was separately evaluated in BACE1 inhibition assays and IC50 values were obtained in the low micromolar range. According to our biological results and docking studies, it can be asserted that the stereochemistry around the OH group in the central hydroxyethylamino linker does not significantly influence the BACE1 inhibitory activity of this type of molecules. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.09.032
• 作为产物：
  描述：

  二苯甲基哌嗪 、 (S)-(+)-对甲苯磺酸缩水甘油酯 在 potassium carbonate 作用下， 以 二甲基亚砜 为溶剂， 反应 24.0h， 以40%的产率得到(R)-1-(diphenylmethyl)-4-(2,3-epoxypropyl)piperazine
  参考文献：
  名称：

  BACE1 inhibitory activities of enantiomerically pure, variously substituted N-(3-(4-benzhydrylpiperazin-1-yl)-2-hydroxypropyl) arylsulfonamides

  摘要：

  beta-Secretase (BACE1) has been widely recognized as one of the possible therapeutic targets for the treatment of Alzheimer's disease. In this paper, we report the synthesis and the BACE1 inhibitory activity of new, variously substituted N-(3-(4-benzhydrylpiperazin-1-yl)-2-hydroxypropyl) arylsulfonamides. Each enantiomeric form was separately evaluated in BACE1 inhibition assays and IC50 values were obtained in the low micromolar range. According to our biological results and docking studies, it can be asserted that the stereochemistry around the OH group in the central hydroxyethylamino linker does not significantly influence the BACE1 inhibitory activity of this type of molecules. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.09.032

文献信息

• Synthesis and Structure-Activity Relationships of 6-Heterocyclic-Substituted Purines as Inactivation Modifiers of Cardiac Sodium Channels
  作者：Kimberly G. Estep、Kurt A. Josef、Edward R. Bacon、Philip M. Carabateas、Squire Rumney、Garry M. Pilling、Douglas S. Krafte、Walter A. Volberg、Kathleen Dillon、Nancy Dugrenier、G. Maurice Briggs、Paul C. Canniff、William P. Gorczyca、Gerald P. Stankus、Alan M. Ezrin

  DOI：10.1021/jm00014a011

  日期：1995.7

  Purine-based analogs of SDZ 211-500 (5) were prepared and evaluated as inactivation modifiers of guinea pig or human cardiac sodium (Na) channels expressed in Xenopus oocytes. Substances which remove or slow the Na channel inactivation process in cardiac tissue are anticipated to prolong the effective refractory period and increase inotropy and thus have potential utility as antiarrhythmic agents. Heterocyclic substitution at the 6-position of the purine ring resulted in compounds with increased Na activity and potency, with 5-membered heterocycles being optimal. Only minor modifications to the benzhydrylpiperazine side chain were tolerated. Selected compounds which delayed the inactivation of Na channels were found to increase refractoriness and contractility in a rabbit Langendorff heart model, consistent with the cellular mechanism. Activity in both the oocyte and rabbit heart assays was specific to the S enantiomers. Preliminary in vivo activity has been demonstrated following intravenous infusion. The most promising compound on the basis of in vitro data is the formylpyrrole (S)-74, which is 25-fold more potent than DPI 201-106 (1) in the human heart Na channel assay.
• BACE1 inhibitory activities of enantiomerically pure, variously substituted N-(3-(4-benzhydrylpiperazin-1-yl)-2-hydroxypropyl) arylsulfonamides
  作者：Simone Bertini、Elisa Ghilardi、Valentina Asso、Carlotta Granchi、Filippo Minutolo、Mauro Pineschi、Valeria Di Bussolo、Andrea Bortolato、Stefano Moro、Alessandro Saba

  DOI：10.1016/j.bmc.2010.09.032

  日期：2010.11.15

  beta-Secretase (BACE1) has been widely recognized as one of the possible therapeutic targets for the treatment of Alzheimer's disease. In this paper, we report the synthesis and the BACE1 inhibitory activity of new, variously substituted N-(3-(4-benzhydrylpiperazin-1-yl)-2-hydroxypropyl) arylsulfonamides. Each enantiomeric form was separately evaluated in BACE1 inhibition assays and IC50 values were obtained in the low micromolar range. According to our biological results and docking studies, it can be asserted that the stereochemistry around the OH group in the central hydroxyethylamino linker does not significantly influence the BACE1 inhibitory activity of this type of molecules. (C) 2010 Elsevier Ltd. All rights reserved.