1-(4-三氟甲基-苄基)-哌啶-4-胺 | 149401-02-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 1-(4-三氟甲基-苄基)-哌啶-4-胺
• 英文名称: 1-(4-(trifluoromethyl)benzyl)piperidin-4-amine
• 英文别名: 4-Amino-1-(4-trifluoromethylbenzyl)piperidine；1-[4-(Trifluoromethyl)benzyl]piperidin-4-amine；1-[[4-(trifluoromethyl)phenyl]methyl]piperidin-4-amine
• CAS: 149401-02-5
• 化学式: C₁₃H₁₇F₃N₂
• mdl: MFCD09971916
• 分子量: 258.287
• InChiKey: IONRLOMCVXWXIJ-UHFFFAOYSA-N

物化性质

• 沸点：
  293.9±40.0 °C(Predicted)
• 密度：
  1.190±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.538
• 拓扑面积：
  29.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(4-三氟甲基-苄基)-哌啶-4-胺 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-(4-trifluoromethylbenzyl)-N-[4,5-bis(4-methoxyphenyl)-thiazol-2-yl]piperidin-4-ylamine
  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 1-(4-三氟甲基-苄基)-哌啶-4-胺
  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
• 作为试剂：
  描述：

  在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 1-(4-三氟甲基-苄基)-哌啶-4-胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成
  参考文献：
  名称：

  WO2014/167371

  摘要：

  公开号：

文献信息

• [EN] TEAD INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DE TEAD ET LEURS UTILISATIONS
  申请人：IKENA ONCOLOGY INC

  公开号：WO2020243423A1

  公开（公告）日：2020-12-03

  The present invention provides compounds, compositions thereof, and methods of using the same.

  本发明提供了化合物、其组合物以及使用它们的方法。
• [EN] ATYPICAL INHIBITORS OF MONOAMINE TRANSPORTERS; METHOD OF MAKING; AND USE THEREOF<br/>[FR] INHIBITEURS ATYPIQUES DE TRANSPORTEURS DE MONOAMINE ; LEUR PROCÉDÉ DE PRODUCTION ET D'UTILISATION
  申请人：US HEALTH

  公开号：WO2019094856A1

  公开（公告）日：2019-05-16

  Disclosed herein are a series of modafinil analogue compounds that bind with moderate to high affinity to the dopamine (DA) transporter (DAT) and several analogues also having affinity for the serotonin (5-HT) transporter (SERT) and/or sigma-1 receptor. Employing aminopiperidine, piperidineamino, spirobicyclodiaza, or substituted piperazine functional groups, desired dopamine transporter affinity has been retained along with improved metabolic stability over unsubstituted piperazine ring analogues. Importantly, these compounds have no predicted addictive liability. Also disclosed are methods for treating substance use disorders as well as other neuropsychiatric disorders such as ADHD, depression, narcolepsy, and cognitive impairment.

  本发明公开了一系列莫达非尼类似物化合物，这些化合物以中等至高亲和力结合多巴胺（DA）转运体（DAT），并且其中几种类似物还对血清素（5-HT）转运体（SERT）和/或σ-1受体具有亲和力。通过使用氨基哌啶、哌啶氨基、螺二氮杂环或取代的哌嗪功能团，不仅保留了对多巴胺转运体的亲和力，而且相对于未取代的哌嗪环类似物，其代谢稳定性得到了改善。重要的是，这些化合物没有预测到的成瘾性。此外，还公开了治疗物质使用障碍以及其他神经精神障碍如注意力缺陷多动障碍（ADHD）、抑郁症、嗜睡症和认知损害的方法。
• Structure-activity relationships for a series of (Bis(4-fluorophenyl)methyl)sulfinylethyl-aminopiperidines and -piperidine amines at the dopamine transporter: Bioisosteric replacement of the piperazine improves metabolic stability
  作者：JoLynn B. Giancola、Alessandro Bonifazi、Jianjing Cao、Therese Ku、Alexandra J. Haraczy、Jenny Lam、Rana Rais、Mark A. Coggiano、Gianluigi Tanda、Amy Hauck Newman

  DOI：10.1016/j.ejmech.2020.112674

  日期：2020.12

  psychostimulant abuse. However, metabolic instability among other limitations to piperazine analogues 1–3 have impeded further development. Herein, bioisosteric substitutions of the piperazine ring were explored with a series of aminopiperidines (A) and piperidine amines (B) wherein compounds with either a terminal tertiary amine or amide were synthesized. Several lead compounds showed high to moderate DAT

  尽管在开发治疗精神兴奋剂使用障碍的药物方面付出了相当大的努力，但没有一种药物被证明是有效的，这使得患者群体服务不足，并且关于开发药物疗法应该针对什么作用机制的问题也没有得到解答。基于 (±) 莫达非尼的非典型多巴胺转运蛋白 (DAT) 抑制剂已在精神兴奋剂滥用的临床前模型中显示出治疗潜力。然而，代谢不稳定以及哌嗪类似物的其他局限性1-3阻碍了进一步的发展。在本文中，用一系列氨基哌啶 (A) 和哌啶胺 (B) 探索了哌嗪环的生物等排取代，其中合成了具有末端叔胺或酰胺的化合物。几种先导化合物在大鼠肝微粒体中显示出高至中等的 DAT 亲和力和代谢稳定性。 与可卡因相比，氨基哌啶7 (DAT K i  = 50.6 nM)、21b (DAT K i  = 77.2 nM) 和33 (DAT K i = 30.0 nM) 仅对小鼠的行走活动产生最小的刺激，表明非典型的 DAT 抑制剂谱.
• 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。
• Synthesis and Preliminary Biological Evaluation of New Phthalazinone Derivatives with PARP-1 and Cholinesterase Inhibitory Activities
  作者：Zhenli Min、Yu Lin、Chengzhi Gao、Zhuyong Wang、Ruifeng Zhang、Yajun Chen

  DOI：10.2174/1570180819666220531144809

  日期：2023.1

  hydrophobic interactions, which were necessary for hBChE inhibitory potency. Conclusion: A new compound with potent PARP-1 inhibitory activity and moderate BChE inhibitory activity was obtained, which merited to be further investigated as an anti-AD drug. The studies gave a clue to search for new agents based on PARP-1 and cholinesterase dual-inhibited activities to treat AD.

  背景：阿尔茨海默氏病 (AD) 是最常见的脑部疾病，并且仍然是全世界的主要健康问题。考虑到 AD 的高度复杂机制，寻找基于多靶点定向配体 (MTDLs) 策略治疗 AD 的药物可能比传统的“一种药物-一种靶点”策略更有前景。抑制聚（ADP-核糖）聚合酶-1 (PARP-1) 对 AD 具有潜在的治疗作用。因此，值得研究同时靶向 PARP-1 和胆碱酯酶的化合物，这可能会产生新的抗 AD 药物。目的：寻找具有 PARP-1 和胆碱酯酶抑制活性的新药治疗 AD。方法：一系列 21 种新化合物结合了两种上市药物的各自药效团，即 PARP-1 抑制剂的 4-苄基酞嗪酮部分，Olaparib 和 AChE 抑制剂多奈哌齐的 Nbenzylpiperidine 部分被合成到一个分子中。评估了所有合成化合物对酶 PARP-1、乙酰胆碱酯酶 (AChE) 和丁酰胆碱酯酶 (BChE) 的抑制活性。通过分子对接研究了