(4-benzhydryl-piperazin-1-yl)-acetonitrile

• 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-benzhydryl-piperazin-1-yl)-acetonitrile
• 英文别名: 2-(4-Benzhydrylpiperazin-1-yl)acetonitrile
• 化学式: C₁₉H₂₁N₃
• 分子量: 291.396
• InChiKey: XNIYRTWNIFGHQX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  30.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (4-benzhydryl-piperazin-1-yl)-acetonitrile 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 生成 2-(4-benzhydrylpiperazin-1-yl)ethan-1-amine
  参考文献：
  名称：

  Synthesis, biological evaluation and molecular docking study of novel piperidine and piperazine derivatives as multi-targeted agents to treat Alzheimer’s disease

  摘要：

  Development of Multi-Target Directed Ligands (MTDLs) has emerged as a promising approach for targeting complex etiology of Alzheimer's disease (AD). Following this approach, a new series of N'-(4-benzylpiperidin-/piperazin-/benzhydrylpiperazin-1-yl) alkylamine derivatives were designed, synthesized and biologically evaluated as inhibitors of cholinesterases (ChEs), amyloid-beta (A beta) self aggregation and also for their radical scavenging activity. The in vitro studies showed that the majority of synthesized derivatives strongly inhibited acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) with IC50 values in the low-nanomolar range, and were clearly more potent than the reference compound donepezil in this regard. Among them, inhibitors 5h and 5k, strongly inhibited AChE, with IC50 value of 6.83 nM and 2.13 nM, respectively, and particularly, compound 5k was found to be highly selective for AChE (similar to 38-fold). Moreover, both kinetic analysis of AChE inhibition and the docking study suggested that 5k binds simultaneously to catalytic active site and peripheral anionic site of AChE. Besides, these compounds also exhibited greater ability to inhibit self-induced A beta(1-42) aggregation at 25 mu M with percentage inhibition from similar to 54% to 89% and specially compound 5k provided highest inhibition (88.81%). Also, the derivatives containing methoxy and hydroxy groups showed potent oxygen radical absorbance capacity (ORAC) ranging from 2.2- to 4.4-fold of the Trolox value. Furthermore, results of ADMET studies suggested that all compounds exhibited appropriate drug like properties. Taken together, these results suggest that 5k might be a promising lead compound for further AD drug development. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.12.057
• 作为产物：
  描述：

  二苯甲基哌嗪 、 溴乙腈 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 2.0h， 生成 (4-benzhydryl-piperazin-1-yl)-acetonitrile
  参考文献：
  名称：

  Synthesis, biological evaluation and molecular docking study of novel piperidine and piperazine derivatives as multi-targeted agents to treat Alzheimer’s disease

  摘要：

  Development of Multi-Target Directed Ligands (MTDLs) has emerged as a promising approach for targeting complex etiology of Alzheimer's disease (AD). Following this approach, a new series of N'-(4-benzylpiperidin-/piperazin-/benzhydrylpiperazin-1-yl) alkylamine derivatives were designed, synthesized and biologically evaluated as inhibitors of cholinesterases (ChEs), amyloid-beta (A beta) self aggregation and also for their radical scavenging activity. The in vitro studies showed that the majority of synthesized derivatives strongly inhibited acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) with IC50 values in the low-nanomolar range, and were clearly more potent than the reference compound donepezil in this regard. Among them, inhibitors 5h and 5k, strongly inhibited AChE, with IC50 value of 6.83 nM and 2.13 nM, respectively, and particularly, compound 5k was found to be highly selective for AChE (similar to 38-fold). Moreover, both kinetic analysis of AChE inhibition and the docking study suggested that 5k binds simultaneously to catalytic active site and peripheral anionic site of AChE. Besides, these compounds also exhibited greater ability to inhibit self-induced A beta(1-42) aggregation at 25 mu M with percentage inhibition from similar to 54% to 89% and specially compound 5k provided highest inhibition (88.81%). Also, the derivatives containing methoxy and hydroxy groups showed potent oxygen radical absorbance capacity (ORAC) ranging from 2.2- to 4.4-fold of the Trolox value. Furthermore, results of ADMET studies suggested that all compounds exhibited appropriate drug like properties. Taken together, these results suggest that 5k might be a promising lead compound for further AD drug development. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.12.057

文献信息

• IMIDAZOPYRIDINE DERIVATIVES AS DUAL HISTAMINE (H1) AND PLATELET ACTIVATING FACTOR (PAF) ANTAGONISTS
  申请人：BRITISH BIOTECH PHARMACEUTICALS LIMITED

  公开号：EP0775139A1

  公开（公告）日：1997-05-28
• METHODS, COMPOSITIONS, AND KITS FOR THE TREATMENT OF CANCER
  申请人：Haggerty Timothy J.

  公开号：US20140335050A1

  公开（公告）日：2014-11-13

  The invention features methods, compositions, and kits for the administration of an HSP90 inhibitor, OBAA, flunarizine, aphidicolin, damnacanthal, dantrolene, or an analog thereof, alone, or in combination with, e.g., a TAA, an antigen-binding scaffold (e.g., an antibody, a soluble T cell receptor, or a chimeric receptor) specific for a TAA, a cell (e.g., a white blood cell that targets a cancer cell), and/or an IFN-β receptor agonist or an IFN-γ receptor agonist, for the treatment of cancer.
• US5753671A
  申请人：——

  公开号：US5753671A

  公开（公告）日：1998-05-19
• [EN] IMIDAZOPYRIDINE DERIVATIVES AS DUAL HISTAMINE (H1) AND PLATELET ACTIVATING FACTOR (PAF) ANTAGONISTS<br/>[FR] DERIVES D'IMIDAZOPYRIDINE UTILISES COMME ANTAGONISTES DU FACTEUR D'ACTIVATION PLAQUETTAIRE (PAF) ET DE LA DOUBLE HISTAMINE (H1)
  申请人：BRITISH BIOTECH PHARMACEUTICALS LIMITED

  公开号：WO1996005201A1

  公开（公告）日：1996-02-22

  (EN) Compounds of formula (II), wherein D is for example a group of formula (X), are dual H1/PAF antagonists.(FR) L'invention se rapporte à des composés de la formule (II) dans laquelle D représente, par exemple, un groupe de la formule (X), ces composés étant des antagonistes de H1/PAF.
• Synthesis, biological evaluation and molecular docking study of novel piperidine and piperazine derivatives as multi-targeted agents to treat Alzheimer’s disease
  作者：Poonam Meena、Vishal Nemaysh、Manisha Khatri、Apra Manral、Pratibha Mehta Luthra、Manisha Tiwari

  DOI：10.1016/j.bmc.2014.12.057

  日期：2015.3

  Development of Multi-Target Directed Ligands (MTDLs) has emerged as a promising approach for targeting complex etiology of Alzheimer's disease (AD). Following this approach, a new series of N'-(4-benzylpiperidin-/piperazin-/benzhydrylpiperazin-1-yl) alkylamine derivatives were designed, synthesized and biologically evaluated as inhibitors of cholinesterases (ChEs), amyloid-beta (A beta) self aggregation and also for their radical scavenging activity. The in vitro studies showed that the majority of synthesized derivatives strongly inhibited acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) with IC50 values in the low-nanomolar range, and were clearly more potent than the reference compound donepezil in this regard. Among them, inhibitors 5h and 5k, strongly inhibited AChE, with IC50 value of 6.83 nM and 2.13 nM, respectively, and particularly, compound 5k was found to be highly selective for AChE (similar to 38-fold). Moreover, both kinetic analysis of AChE inhibition and the docking study suggested that 5k binds simultaneously to catalytic active site and peripheral anionic site of AChE. Besides, these compounds also exhibited greater ability to inhibit self-induced A beta(1-42) aggregation at 25 mu M with percentage inhibition from similar to 54% to 89% and specially compound 5k provided highest inhibition (88.81%). Also, the derivatives containing methoxy and hydroxy groups showed potent oxygen radical absorbance capacity (ORAC) ranging from 2.2- to 4.4-fold of the Trolox value. Furthermore, results of ADMET studies suggested that all compounds exhibited appropriate drug like properties. Taken together, these results suggest that 5k might be a promising lead compound for further AD drug development. (C) 2014 Elsevier Ltd. All rights reserved.