4-amino-1-(2-chloro-4-fluorobenzyl)piperidine | 380424-72-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 4-amino-1-(2-chloro-4-fluorobenzyl)piperidine
• 英文别名: 1-[(2-Chloro-4-fluorophenyl)methyl]piperidin-4-amine
• CAS: 380424-72-6
• 化学式: C₁₂H₁₆ClFN₂
• mdl: MFCD12137398
• 分子量: 242.724
• InChiKey: WLMUBAJRXMQQNI-UHFFFAOYSA-N

物化性质

• 沸点：
  311.7±42.0 °C(Predicted)
• 密度：
  1.216±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  29.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-amino-1-(2-chloro-4-fluorobenzyl)piperidine 在 sodium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 5.0h， 生成 1-(2-chloro-4-fluorobenzyl)piperidin-4-ylthiourea
  参考文献：
  名称：

  Benzylpiperidine-Linked Diarylthiazoles as Potential Anti-Alzheimer’s Agents: Synthesis and Biological Evaluation

  摘要：

  A novel series of hybrid molecules were designed and synthesized by fusing the pharmacophoric features of cholinesterase inhibitor donepezil and diarylthiazole as potential multitarget-directed ligands for the treatment of Alzheimer's disease (AD). The compounds showed significant in vitro anticholinesterase (anti-ChE) activity, the most potent compound (44) among them showing the highest activity (IC50 value of 0.30 +/- 0.01 mu M) for AChE and (1.84 +/- 0.03 mu M) for BuChE. Compound 44 showed mixed inhibition of AChE in the enzyme kinetic studies. Some compounds exhibited moderate to high inhibition of AChE-induced A beta(1-42) aggregation and noticeable in vitro antioxidant and antiapoptotic properties. Compound 44 showed significant in vivo anti-ChE and antioxidant activities. Furthermore, compound 44 demonstrated in vivo neuroprotection by decreasing A beta(1-42)-induced toxicity by attenuating abnormal levels of A beta(1-42), p-Tau, cleaved caspase-3, and cleaved PARP proteins. Compound 44 exhibited good oral absorption and was well tolerated up to 2000 mg/kg, po, dose without showing toxic effects.

  DOI：

  10.1021/acs.jmedchem.6b00426
• 作为产物：
  描述：

  哌啶-4-甲酰胺 在 potassium carbonate 、 [双(三氟乙酰氧基)碘]苯 作用下， 以 甲醇 、 水 、 乙腈 为溶剂， 生成 4-amino-1-(2-chloro-4-fluorobenzyl)piperidine
  参考文献：
  名称：

  Benzylpiperidine-Linked Diarylthiazoles as Potential Anti-Alzheimer’s Agents: Synthesis and Biological Evaluation

  摘要：

  A novel series of hybrid molecules were designed and synthesized by fusing the pharmacophoric features of cholinesterase inhibitor donepezil and diarylthiazole as potential multitarget-directed ligands for the treatment of Alzheimer's disease (AD). The compounds showed significant in vitro anticholinesterase (anti-ChE) activity, the most potent compound (44) among them showing the highest activity (IC50 value of 0.30 +/- 0.01 mu M) for AChE and (1.84 +/- 0.03 mu M) for BuChE. Compound 44 showed mixed inhibition of AChE in the enzyme kinetic studies. Some compounds exhibited moderate to high inhibition of AChE-induced A beta(1-42) aggregation and noticeable in vitro antioxidant and antiapoptotic properties. Compound 44 showed significant in vivo anti-ChE and antioxidant activities. Furthermore, compound 44 demonstrated in vivo neuroprotection by decreasing A beta(1-42)-induced toxicity by attenuating abnormal levels of A beta(1-42), p-Tau, cleaved caspase-3, and cleaved PARP proteins. Compound 44 exhibited good oral absorption and was well tolerated up to 2000 mg/kg, po, dose without showing toxic effects.

  DOI：

  10.1021/acs.jmedchem.6b00426

文献信息

• 6,9-disubstituted 2-[trans-(4-aminocyclohexyl) amino] purines
  申请人：——

  公开号：US20030105098A1

  公开（公告）日：2003-06-05

  The present invention comprises 6-9-Disubstituted 2-[trans-(4-aminocyclohexyl]aminopurines that are useful in inhibiting cyclin dependent kinases, particularly cdk-2. The present invention also provides a method of preventing apoptosis in neuronal cells and a method of inhibiting the development of neoplasms.

  本发明涉及6-9-二取代的2- [转-（4-氨基环己基）]氨基嘌呤，其在抑制细胞周期依赖性激酶，特别是cdk-2方面具有用途。本发明还提供了一种预防神经细胞凋亡和抑制肿瘤发展的方法。
• THE DESIGN AND SYNTHESIS OF PURINE INHIBITORS OF CDK2. III
  作者：P. W. Shum、N. P. Peet、P. M. Weintraub、T. B. Le、Z. Zhao、F. Barbone、B. Cashman、J. Tsay、S. Dwyer、P. C. Loos、E. A. Powers、K. Kropp、P. S. Wright、A. Bitonti、J. Dumont、D. R. Borcherding

  DOI：10.1081/ncn-100002493

  日期：2001.3.31

  Cyclin-dependent kinases (CDKs) belong to a class of enzymes that control the ability of a cell to enter into and proceed through the cell division cycle. Using purine as a scaffold, we have synthesized a number of nanomolar inhibitors of CDK-2/cyclin E. In this report, the synthesis of a series of piperidine-substituted purine analogs will be presented, as well as some of their in vitro and in vivo biological effects.
• 6,9-DISUBSTITUTED 2- TRANS-(4- AMINOCYCLOHEXYL) AMINO]PURINES
  申请人：Aventis Pharmaceuticals Inc.

  公开号：EP1056744B1

  公开（公告）日：2003-10-22
• US6479487B1
  申请人：——

  公开号：US6479487B1

  公开（公告）日：2002-11-12
• US6642231B2
  申请人：——

  公开号：US6642231B2

  公开（公告）日：2003-11-04