N-tert-Butoxycarbonyl-O-benzyl-5-hydroxytryptamin | 53157-47-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: N-tert-Butoxycarbonyl-O-benzyl-5-hydroxytryptamin
• 英文别名: [2-(5-benzyloxy-indol-3-yl)-ethyl]-carbamic acid tert-butyl ester；tert-butyl N-[2-(5-phenylmethoxy-1H-indol-3-yl)ethyl]carbamate
• CAS: 53157-47-4
• 化学式: C₂₂H₂₆N₂O₃
• 分子量: 366.46
• InChiKey: HYBQVULJXCDZMI-UHFFFAOYSA-N

物化性质

• 沸点：
  569.6±45.0 °C(Predicted)
• 密度：
  1.166±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  63.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-tert-Butoxycarbonyl-O-benzyl-5-hydroxytryptamin 在 1-羟基苯并三唑 、 溶剂黄146 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 1-(1-Methyl-6-phenylmethoxy-1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl)-2-phenylethanone
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Novel Tetrahydro-β-carboline Derivatives as Antitumor Growth and Metastasis Agents through Inhibiting the Transforming Growth Factor-β Signaling Pathway

  摘要：

  The transforming growth factor beta (TGF beta) signaling cascade is considered as one of the pivotal oncogenic pathways in most advanced cancers. Inhibition of the TGF beta signaling pathway by specific antagonists, neutralizing antibodies, or small molecules is considered as an effective strategy for the treatment of tumor growth and metastasis. Here we demonstrated the identification of a series of tetrahydro-beta-carboline derivatives from virtual screening which potentially inhibit the TGF beta signaling pathway. Optimization of the initial hit compound 2-benzoyl-1,3,4,9-tetrahydro-beta-carboline (8a) through substitution at different positions to define the structure-activity relationship resulted in the discovery of potent inhibitors of the TGF beta signaling pathway. Among them, compound 8d, one of the tested compounds, not only showed potent inhibition of lung cancer cell proliferation and migration in vitro but also strongly suppressed growth of lung cancer and breast cancer in vivo.

  DOI：

  10.1021/jm401117t
• 作为产物：
  描述：

  5-羟基色胺盐酸盐 在 碳酸氢钠 、 caesium carbonate 、 sodium chloride 作用下， 以 氯仿 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 N-tert-Butoxycarbonyl-O-benzyl-5-hydroxytryptamin
  参考文献：
  名称：

  Optimization of 5-hydroxytryptamines as dual function inhibitors targeting phospholipase A2 and leukotriene A4 hydrolase

  摘要：

  Dual function inhibitors targeting phospholipase A(2) (PLA(2)) and leukotriene A(4) hydrolase (LTA(4)H) may balance the arachidonic acid (AA) metabolic network and be used as new anti-inflammatory drugs. In previous study, we discovered multi-target drugs towards the AA metabolic network, among which a dual-target inhibitor (JMC08-4) for human nonpancreatic secretory phospholipase A(2) (hnps-PLA(2)) and human leukotriene A(4) hydrolase (LTA(4)H-h) was found. Based on the structure of compound JMC08-4, new dual-target inhibitors were designed assisted by molecular docking. In this report, a series of 5-hydroxytryptamine compounds were synthesized; and most of these title compounds showed more potent inhibitory activity than compound JMC08-4 in the in vitro bioassay against these two enzymes. The best one inhibited hnps-PLA(2) and LTA(4)H-h with IC50 values of 9.2 +/- 0.5 mu M and 2.4 +/- 1.4 mu M, respectively. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.10.057

文献信息

• Chiral phosphoric acid catalyzed enantioselective <i>N</i>-alkylation of indoles with <i>in situ</i> generated cyclic <i>N</i>-acyl ketimines
  作者：Lvye Zhang、Binqiang Wu、Zhangtao Chen、Jinjin Hu、Xiaofei Zeng、Guofu Zhong

  DOI：10.1039/c8cc05073b

  日期：——

  A chiral SPINOL derived phosphoric acid-catalyzed asymmetric N-alkylation reaction of indoles with cyclic α-diaryl-substituted N-acyl imines, which are generated in situ from 3-aryl 3-hydroxyisoindolinones, has been demonstrated. The transformation proceeds smoothly with a broad range of indoles and isoindolinone alcohols. A variety of indole derived N-alkylated tetrasubstituted chiral aminals were

  已经证明手性SPINOL衍生的吲哚与环α-二芳基取代的N-酰基亚胺的吲哚的磷酸不对称N-烷基化反应是由3-芳基3-羟基异吲哚满酮原位产生的。使用多种吲哚和异吲哚啉酮醇可顺利进行转化。各种吲哚衍生的N-烷基化的四取代手性缩醛胺均以中等至良好的收率（50-79％）提供，并具有出色的对映选择性（可达98％ee）。
• Synthesis and Biological Evaluation of Novel Tetrahydro-β-carboline Derivatives as Antitumor Growth and Metastasis Agents through Inhibiting the Transforming Growth Factor-β Signaling Pathway
  作者：Cong Zheng、Yuanzhang Fang、Weiguang Tong、Guoliang Li、Haigang Wu、Wenbo Zhou、Qingxiang Lin、Feifei Yang、Zhengfeng Yang、Peng Wang、Yangrui Peng、Xiufeng Pang、Zhengfang Yi、Jian Luo、Mingyao Liu、Yihua Chen

  DOI：10.1021/jm401117t

  日期：2014.2.13

  The transforming growth factor beta (TGF beta) signaling cascade is considered as one of the pivotal oncogenic pathways in most advanced cancers. Inhibition of the TGF beta signaling pathway by specific antagonists, neutralizing antibodies, or small molecules is considered as an effective strategy for the treatment of tumor growth and metastasis. Here we demonstrated the identification of a series of tetrahydro-beta-carboline derivatives from virtual screening which potentially inhibit the TGF beta signaling pathway. Optimization of the initial hit compound 2-benzoyl-1,3,4,9-tetrahydro-beta-carboline (8a) through substitution at different positions to define the structure-activity relationship resulted in the discovery of potent inhibitors of the TGF beta signaling pathway. Among them, compound 8d, one of the tested compounds, not only showed potent inhibition of lung cancer cell proliferation and migration in vitro but also strongly suppressed growth of lung cancer and breast cancer in vivo.
• Optimization of 5-hydroxytryptamines as dual function inhibitors targeting phospholipase A2 and leukotriene A4 hydrolase
  作者：Hu Meng、Ying Liu、Yujing Zhai、Luhua Lai

  DOI：10.1016/j.ejmech.2012.10.057

  日期：2013.1

  Dual function inhibitors targeting phospholipase A(2) (PLA(2)) and leukotriene A(4) hydrolase (LTA(4)H) may balance the arachidonic acid (AA) metabolic network and be used as new anti-inflammatory drugs. In previous study, we discovered multi-target drugs towards the AA metabolic network, among which a dual-target inhibitor (JMC08-4) for human nonpancreatic secretory phospholipase A(2) (hnps-PLA(2)) and human leukotriene A(4) hydrolase (LTA(4)H-h) was found. Based on the structure of compound JMC08-4, new dual-target inhibitors were designed assisted by molecular docking. In this report, a series of 5-hydroxytryptamine compounds were synthesized; and most of these title compounds showed more potent inhibitory activity than compound JMC08-4 in the in vitro bioassay against these two enzymes. The best one inhibited hnps-PLA(2) and LTA(4)H-h with IC50 values of 9.2 +/- 0.5 mu M and 2.4 +/- 1.4 mu M, respectively. (C) 2012 Elsevier Masson SAS. All rights reserved.