4-(4-aminopiperidin-1-yl)-2,2-diphenylbutanenitrile | 1412903-11-7

• 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: 4-(4-aminopiperidin-1-yl)-2,2-diphenylbutanenitrile
• 英文别名: 4-(4-Aminopiperidin-1-yl)-2,2-diphenylbutanenitrile
• CAS: 1412903-11-7
• 化学式: C₂₁H₂₅N₃
• 分子量: 319.45
• InChiKey: MYUNWKYEAPYPNH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  53
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(4-aminopiperidin-1-yl)-2,2-diphenylbutanenitrile 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 以55%的产率得到1-(4-amino-3,3-diphenylbutyl)piperidin-4-amine
  参考文献：
  名称：

  Overcoming chloroquine resistance in malaria: Design, synthesis and structure–activity relationships of novel chemoreversal agents

  摘要：

  Malaria remains a significant infectious disease with even artemisinin-based therapies now facing resistance in the field. Development of new therapies is urgently needed, either by finding new compounds with unique modes of action, or by reversing resistance towards known drugs with 'chemosensitizers' or 'chemoreversal' agents (CRA). Concerning the latter, we have focused on the resistance mechanisms developed against chloroquine (CQ). We have synthesized a series of compounds related to previously identified CRAs, and found promising novel compounds. These compounds show encouraging results in a coumarin labeled chloroquine uptake assay, exhibiting a dose response in resensitising parasites to the antimalarial effects of chloroquine. Selected compounds show consistent potency across a panel of chloroquine and artemisinin sensitive and resistant parasites, and a wide therapeutic window. This data supports further study of CRAs in the treatment of malaria and, ultimately, their use in chloroquine-based combination therapies. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.04.058
• 作为产物：
  描述：

  tert-butyl (1-(3-cyano-3,3-diphenylpropyl)piperidin-4-yl)carbamate 在 potassium hydroxide 作用下， 以 叔丁醇 为溶剂， 以62%的产率得到4-(4-aminopiperidin-1-yl)-2,2-diphenylbutanenitrile
  参考文献：
  名称：

  Overcoming chloroquine resistance in malaria: Design, synthesis and structure–activity relationships of novel chemoreversal agents

  摘要：

  Malaria remains a significant infectious disease with even artemisinin-based therapies now facing resistance in the field. Development of new therapies is urgently needed, either by finding new compounds with unique modes of action, or by reversing resistance towards known drugs with 'chemosensitizers' or 'chemoreversal' agents (CRA). Concerning the latter, we have focused on the resistance mechanisms developed against chloroquine (CQ). We have synthesized a series of compounds related to previously identified CRAs, and found promising novel compounds. These compounds show encouraging results in a coumarin labeled chloroquine uptake assay, exhibiting a dose response in resensitising parasites to the antimalarial effects of chloroquine. Selected compounds show consistent potency across a panel of chloroquine and artemisinin sensitive and resistant parasites, and a wide therapeutic window. This data supports further study of CRAs in the treatment of malaria and, ultimately, their use in chloroquine-based combination therapies. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.04.058

文献信息

• Structure–activity relationship exploration of Kv1.3 blockers based on diphenoxylate
  作者：William Nguyen、Brittany L. Howard、David P. Jenkins、Heike Wulff、Philip E. Thompson、David T. Manallack

  DOI：10.1016/j.bmcl.2012.09.080

  日期：2012.12

  Diphenoxylate, a well-known opioid agonist and anti-diarrhoeal agent, was recently found to block Kv1.3 potassium channels, which have been proposed as potential therapeutic targets for a range of autoimmune diseases. The molecular basis for this Kv1.3 blockade was assessed by the selective removal of functional groups from the structure of diphenoxylate as well as a number of other structural variations. Removal of the nitrile functional group and replacement of the C-4 piperidinyl substituents resulted in several compounds with submicromolar IC50 values. (C) 2012 Elsevier Ltd. All rights reserved.
• Overcoming chloroquine resistance in malaria: Design, synthesis and structure–activity relationships of novel chemoreversal agents
  作者：Aicha Boudhar、Xiao Wei Ng、Chiew Yee Loh、Wan Ni Chia、Zhi Ming Tan、Francois Nosten、Brian W. Dymock、Kevin S.W. Tan

  DOI：10.1016/j.ejmech.2016.04.058

  日期：2016.8

  Malaria remains a significant infectious disease with even artemisinin-based therapies now facing resistance in the field. Development of new therapies is urgently needed, either by finding new compounds with unique modes of action, or by reversing resistance towards known drugs with 'chemosensitizers' or 'chemoreversal' agents (CRA). Concerning the latter, we have focused on the resistance mechanisms developed against chloroquine (CQ). We have synthesized a series of compounds related to previously identified CRAs, and found promising novel compounds. These compounds show encouraging results in a coumarin labeled chloroquine uptake assay, exhibiting a dose response in resensitising parasites to the antimalarial effects of chloroquine. Selected compounds show consistent potency across a panel of chloroquine and artemisinin sensitive and resistant parasites, and a wide therapeutic window. This data supports further study of CRAs in the treatment of malaria and, ultimately, their use in chloroquine-based combination therapies. (C) 2016 Elsevier Masson SAS. All rights reserved.