1-benzyl-N-phenethylpiperidin-4-amine | 167626-23-5

• 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: 1-benzyl-N-phenethylpiperidin-4-amine
• 英文别名: (1-benzyl-piperidin-4-yl)-phenethyl-amine；4-(2-phenylethylamino)-1-benzylpiperidine；1-Benzyl-4-(phenethylamino)piperidin；1-benzyl-N-(2-phenylethyl)piperidin-4-amine
• CAS: 167626-23-5
• 化学式: C₂₀H₂₆N₂
• mdl: MFCD01467777
• 分子量: 294.44
• InChiKey: HPMXEBPOHLVJNH-UHFFFAOYSA-N

物化性质

• 沸点：
  422.8±40.0 °C(Predicted)
• 密度：
  1.06±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  15.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-benzyl-N-phenethylpiperidin-4-amine 在 甲酸 、 diethylphosphoryl cyanide 、 水 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 50.0 ℃ 、101.33 kPa 条件下， 反应 4.5h， 生成 8-(4-(N-methyl-2-phenylethyl)amino-1-piperidinyl)carbonyl-2(1H)-quinolinone
  参考文献：
  名称：

  Novel Selective Hindlimb Vasodilators:  Synthesis and Biological Activity of 1-Acyl-4-aminopiperidine Derivatives

  摘要：

  A series of 6-(4-amino-1-piperidinyl)carbonyl-2(1H)-quinolinones, and their open form derivatives, were synthesized and evaluated for their ability to stimulate femoral artery blood flow (FBF) in the canine hindlimb. All members of this series stimulated FBF, and subsequent experiments revealed that selected members of this series produced minimal changes in coronary blood flow or systemic blood pressure. Compound 25 was the most promising agent in this respect, and clinical trials are now ongoing to evaluate the effectiveness of this drug as a novel treatment for intermittent claudication and Raynaud's phenomenon.

  DOI：

  10.1021/jm020597o
• 作为产物：
  描述：

  1-benzyl-N-(2-phenylethyl)piperidin-4-imine 生成 1-benzyl-N-phenethylpiperidin-4-amine
  参考文献：
  名称：

  Peripheral vasodilating agent containing piperidine derivative as active

  摘要：

  本发明涉及一种新型周围血管扩张剂，其特征在于每种扩张剂均含有一种活性成分，即一种具有优异周围血管扩张活性的哌啶衍生物或其药学上可接受的盐。所述哌啶衍生物或其药学上可接受的盐由通式（1）表示：##STR1##（其中，R、R.sup.1和R.sup.2与上述定义相同）。

  公开号：

  US06136826A1

文献信息

• 一种香豆素类化合物及其制备方法和应用
  申请人：南京易腾药物研究院有限公司

  公开号：CN112939971B

  公开（公告）日：2023-01-24

  本发明公开了具有不同通式结构的香豆素类化合物及其药学上可接受的盐、溶剂化物、多晶型物、互变异构体、代谢产物或前药。本发明还公开了上述化合物作为NEDD8激活酶抑制剂的作用以及在制备用于治疗与NEDD8激活酶异常有关的疾病的药物中的用途。本发明还公开了用于制备上述香豆素类化合物的中间体及其制备方法。药理结果显示，该化合物具有良好的NEDD8抑制活性、抗肿瘤细胞增殖作用、促进肿瘤细胞凋亡作用。
• Design, Synthesis and Biological Evaluation of Coumarin Derivatives as NEDD8 Activating Enzyme Inhibitors in Pancreatic Cancer Cells
  作者：Yubin Wang、Lei Gong、Peng Lu、Cheng Lu、Mengli Li、Huiyang Wan

  DOI：10.2174/1573406418666211210163817

  日期：2022.7

  NEDD8 (neural precursor cell expressed developmentally downregulated protein 8) is one of the ubiquitin-like proteins which is activated by the NEDD8 activating enzyme (NAE). The overexpressed NAE can cause a variety of diseases such as numerous cancer types and inflammatory diseases. The selective inhibition of NAE could mediate the rate of ubiquitination and the subsequent degradation of proteins associated with cancer so as to achieve the purpose of treatment.

  In this article, we decided to study the synthesis and screening of coumarin scaffold derivatives against cancer cell lines, specifically the human pancreatic cancer cell line BxPC-3.

  Twenty-four targeted compounds were synthesized, and their anti-proliferative activity against three cancer cell lines, cytotoxicity against three normal cell lines through CCK-8 and MTT assay were evaluated to screen out the candidate compound. Then the target was further confirmed by both enzyme and cell-based experiments, as well as cell apoptosis research.

  Several new 4-position substituted coumarin derivatives (12a~x) were synthesized and most of them exhibit antiproliferative activity in three cancer cell lines. A series of experiments were performed to identify the best candidate compound 12v. This compound displayed the highest potency against BxPC-3 with an IC50 value of 0.28 μM. It can also inhibit NAE activity in enzyme and cellbased assay, and induce CRLs-mediated accumulation of the substrate and apoptosis in BxPC-3 cells. Meanwhile, it exhibited relatively low toxicity in three normal cells.

  Based on these results, we found that compound 12v inhibited NAE activity in enzyme and cell-based systems and induced apoptosis in BxPC-3 cells. Additionally, it also had a low toxicity. These results suggested that 12v may be promising lead compounds for the development of new anticancer drugs.

  背景：NEDD8（神经前体细胞表达发育下调蛋白8）是一种类似泛素的蛋白质之一，由NEDD8激活酶（NAE）激活。过表达的NAE可能导致多种疾病，如多种癌症类型和炎症性疾病。选择性抑制NAE可以调节泛素化速率和与癌症相关的蛋白质的后续降解，从而实现治疗目的。 目的：在本文中，我们决定研究库马林骨架衍生物针对癌细胞系的合成和筛选，特别是人胰腺癌细胞系BxPC-3。 方法：合成了24种靶向化合物，并通过CCK-8和MTT分析评估它们对三种癌细胞系的抗增殖活性，对三种正常细胞系的细胞毒性，以筛选出候选化合物。然后通过酶和基于细胞的实验以及细胞凋亡研究进一步确认目标。 结果：合成了几种新的4-位取代库马林衍生物（12a~x），其中大多数在三种癌细胞系中表现出抗增殖活性。进行了一系列实验以确定最佳候选化合物12v。该化合物对BxPC-3显示出最高的活性，IC50值为0.28μM。它还可以在酶和基于细胞的实验中抑制NAE活性，并诱导CRLs介导的底物积累和BxPC-3细胞凋亡。同时，它在三种正常细胞中显示出相对较低的毒性。 结论：根据这些结果，我们发现化合物12v在酶和基于细胞的系统中抑制了NAE活性，并在BxPC-3细胞中诱导了凋亡。此外，它还具有较低的毒性。这些结果表明，12v可能是新抗癌药物开发的有希望的先导化合物。
• 一种4-取代的吡啶并[2,3-d]嘧啶-7-酮类化合物及其制备方法和应用
  申请人：南京思聚生物医药有限公司

  公开号：CN112851671B

  公开（公告）日：2022-03-29

  本发明公开了具有不同通式结构的4‑取代的吡啶并[2,3‑d]嘧啶‑7‑酮类化合物及其药学上可接受的盐、溶剂化物、多晶型物、互变异构体、代谢产物或前药。本发明还公开了上述化合物作为NEDD8激活酶抑制剂的作用以及在制备用于治疗与NEDD8激活酶异常有关的疾病的药物中的用途。药理结果显示，该化合物具有良好的NEDD8抑制活性、抗肿瘤细胞增殖作用、促进肿瘤细胞凋亡作用。
• [EN] PERIPHERAL VASODILATING AGENT CONTAINING N-ACYLATED 4-AMINO PIPERIDINE DERIVATIVES AS ACTIVE INGREDIENTS<br/>[FR] AGENTS VASODILATATEURS PERIPHERIQUES COMPORTANT COMME PRINCIPE ACTIF DES DERIVES DE LA PIPERIDINE 4-AMINO N-ACYLEE
  申请人：OTSUKA PHARMACEUTICAL CO., LTD.

  公开号：WO1994022826A1

  公开（公告）日：1994-10-13

  (EN) The present invention relates to novel peripheral vasodilating agents characterized by each containing as an active ingredient, a piperidine derivative or pharmaceutically acceptable salt thereof having excellent peripheral vasodilating activity. Said piperidine derivative or pharmaceutically acceptable salt thereof is represented by general formula (1), wherein R, R1 and R2 are the same as defined above.(FR) Nouveaux agents dilatateurs périphériques contenant individuellement comme principe actif un dérivé de la pipéridine ou l'un de ses sels pharmaco-compatibles et présentant une excellente activité vasodilatatrice périphérique. Lesdits dérivés de la pipéridine ou leurs sels pharmaco-compatibles sont représentés par la formule générale (1) où R, R1 et R2 sont conformes à la définition ci-dessus.

  (EN) 本发明涉及一种新型周围血管扩张剂，其特征在于每种扩张剂均包含作为活性成分的哌啶衍生物或其药学上可接受的盐，具有出色的周围血管扩张活性。所述哌啶衍生物或其药学上可接受的盐由通式（1）表示，其中R，R1和R2与上述定义相同。 (FR) La présente invention concerne de nouveaux agents vasodilatateurs périphériques caractérisés chacun par la présence, en tant que principe actif, d'un dérivé de pipéridine ou de l'un de ses sels pharmaceutiquement acceptables présentant une excellente activité vasodilatatrice périphérique. Lesdits dérivés de pipéridine ou leurs sels pharmaceutiquement acceptables sont représentés par la formule générale (1), dans laquelle R, R1 et R2 sont tels que définis ci-dessus.
• A novel NAE/UAE dual inhibitor LP0040 blocks neddylation and ubiquitination leading to growth inhibition and apoptosis of cancer cells
  作者：Peng Lu、Yahui Guo、Lijuan Zhu、Yineng Xia、Yuejiao Zhong、Yubin Wang

  DOI：10.1016/j.ejmech.2018.05.027

  日期：2018.6

  NEDD8 activating enzyme (NAE) plays an important role in regulating intracellular proteins with key parts in a broad array of cellular functions. On the basis of previously work, a series of 2H-chromen-2-one based NAE inhibitors were designed and synthesized. Through enzyme-based and cell-based assays, LP0040 was identified as a non-nucleoside NAE/UAE dual inhibitor, It could inhibit NAE/UAE activities and downregulated degradations of related substrates in AGS cells, promoting apoptosis in low micro mole concentrations. LP0040 possessed anti-proliferation activities with IC50 values of 0.76-3.29 mu M against multiple human cancer lines and had synergistic effect with bortezomib. Thus LP0040 represented valuable starting points for future development of NAE/UAE dual inhibitors. (C) 2018 Elsevier Masson SAS. All rights reserved.