6-(benzyloxy)-2,3,4,9-tetrahydro-1H-β-carbolin-1-one | 51086-22-7

• 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: 6-(benzyloxy)-2,3,4,9-tetrahydro-1H-β-carbolin-1-one
• 英文别名: kb-NB123-52；6-(Benzyloxy)-2,3,4,9-tetrahydro-1H-beta-carbolin-1-one；6-phenylmethoxy-2,3,4,9-tetrahydropyrido[3,4-b]indol-1-one
• CAS: 51086-22-7
• 化学式: C₁₈H₁₆N₂O₂
• 分子量: 292.337
• InChiKey: GFULUZWYBKHEKQ-UHFFFAOYSA-N

物化性质

• 熔点：
  195-197 °C
• 沸点：
  615.5±55.0 °C(Predicted)
• 密度：
  1.293±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  54.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-(benzyloxy)-2,3,4,9-tetrahydro-1H-β-carbolin-1-one 在 palladium on activated charcoal 甲酸铵 作用下， 以 甲醇 为溶剂， 反应 1.0h， 生成 2,3,4,9-四氢-6-羟基-1H-吡啶并[3,4-b]吲哚-1-酮
  参考文献：
  名称：

  From pyrroles to 1-oxo-2,3,4,9-tetrahydro-1H-β-carbolines: A new class of orally bioavailable mGluR1 antagonists

  摘要：

  Exploiting the SAR of the known pyrrole derivatives, a new class of mGluR1 antagonists was designed by replacement of the pyrrole core with an indole scaffold and consequent cyclization of the C-2 position into a tricyclic beta-carboline template. The appropriate exploration of the position C-6 with a combination of H-bond acceptor groups coupled with bulky/lipophilic moieties led to the discovery of a new series of mGluR1 antagonists. These compounds exhibited a non-competitive behavior, excellent pharmacokinetic properties, and good in vivo activity in animal models of acute and chronic pain, after oral administration. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.01.055
• 作为产物：
  描述：

  4-苄氧基苯胺 在 盐酸 、 甲酸 、 sodium nitrite 作用下， 以 水 为溶剂， 反应 12.5h， 生成 6-(benzyloxy)-2,3,4,9-tetrahydro-1H-β-carbolin-1-one
  参考文献：
  名称：

  旋光性乙二胺衍生物：不对称合成和抗肿瘤活性

  摘要：

  Evodiamine及其衍生物在C13b位置具有不对称中心。在此，通过简单的不对称全合成获得了evodiamine衍生物2和3的异构体。评估了它们对拓扑异构酶I和II的抑制活性以及它们在癌细胞系中的细胞毒性。所有四种异构体均表现出良好至优异的抗肿瘤效力，并且（S）-异构体通常比（R）-异构体更具活性。（S）-2与拓扑异构酶I和II的结合模式也通过分子对接得以阐明。

  DOI：

  10.1016/j.cclet.2014.11.011

文献信息

• PROTEIN KINASE D INHIBITORS
  申请人：Wipf Peter

  公开号：US20140045821A1

  公开（公告）日：2014-02-13

  Compounds according to Formula (I), are potent inhibitors of protein kinase D (pan-PKD) activity. PKD controls key signaling cascades in cells, affecting cell proliferation, gene transcription, and protein trafficking. Accordingly, pharmaceutically acceptable compositions of the inventive compounds are candidate therapeutics for pathological conditions conditioned by changes in PKD activity.

  根据式(I)，化合物是蛋白激酶D(pan-PKD)活性的有效抑制剂。PKD控制着细胞中的关键信号级联，影响细胞增殖、基因转录和蛋白质运输。因此，这些创新化合物的药学合适组合物是治疗PKD活性改变引起的病理情况的候选药物。
• INDOLE COMPOUND
  申请人：Astellas Pharma Inc.

  公开号：EP3095781B1

  公开（公告）日：2018-10-03
• New Tricks for an Old Natural Product: Discovery of Highly Potent Evodiamine Derivatives as Novel Antitumor Agents by Systemic Structure–Activity Relationship Analysis and Biological Evaluations
  作者：Guoqiang Dong、Shengzheng Wang、Zhenyuan Miao、Jianzhong Yao、Yongqiang Zhang、Zizhao Guo、Wannian Zhang、Chunquan Sheng

  DOI：10.1021/jm300605m

  日期：2012.9.13

  Evodiamine is a quinazolinocarboline alkaloid isolated from the fruits of traditional Chinese herb Evodiae fructus. Previously, we identified N13-substituted evodiamine derivatives as potent topoisomerase I inhibitors by structure-based virtual screening and lead optimization. Herein, a library of novel evodiamine derivatives bearing various substitutions or modified scaffold were synthesized. Among them, a number of evodiamine derivatives showed substantial increase of the antitumor activity, with GI(50) values lower than 3 nM. Moreover, these highly potent compounds can effectively induce the apoptosis of A549 cells. Interestingly, further computational target prediction calculations in combination with biological assays confirmed that the evodiamine derivatives acted by dual inhibition of topoisomerases I and II. Moreover, several hydroxyl derivatives, such as 10-hydroxyl evodiamine (10j) and 3-amino-10-hydroxyl evodiamine (18g), also showed good in vivo antitumor efficacy and low toxicity at the dose of 1 mg/kg or 2 mg/kg. They represent promising candidates for the development of novel antitumor agents.
• 880. Tryptamines, carbolines, and related compounds. Part II. A convenient synthesis of tryptamines and β-carbolines
  作者：R. A. Abramovitch、D. Shapiro

  DOI：10.1039/jr9560004589

  日期：——
• NARAYANAN, KRISHNASWAMY;SCHINDLER, LIESL;COOK, JAMES M., J. ORG. CHEM., 56,(1991) N, C. 359-365
  作者：NARAYANAN, KRISHNASWAMY、SCHINDLER, LIESL、COOK, JAMES M.

  DOI：——

  日期：——