3-{[4-(benzyloxy)phenyl]hydrazono}piperidin-2-one | 101783-07-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-{[4-(benzyloxy)phenyl]hydrazono}piperidin-2-one
• 英文别名: 3-[(4-Phenylmethoxyphenyl)hydrazinylidene]piperidin-2-one；3-[(4-phenylmethoxyphenyl)hydrazinylidene]piperidin-2-one
• CAS: 101783-07-7
• 化学式: C₁₈H₁₉N₃O₂
• 分子量: 309.368
• InChiKey: HQQQZXXGKGBDOP-UHFFFAOYSA-N

物化性质

• 熔点：
  165-168 °C
• 密度：
  1.21±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  62.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-{[4-(benzyloxy)phenyl]hydrazono}piperidin-2-one 在 甲酸 、 水 、 potassium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 8.0h， 生成 3-(2-aminoethyl)-5-(benzyloxy)-1H-indole-2-carboxylic acid
  参考文献：
  名称：

  INDOLE COMPOUND

  摘要：

  公开号：

  EP3095781B1
• 作为产物：
  描述：

  4-苄氧基苯胺 在 盐酸 、 sodium nitrite 作用下， 以 水 为溶剂， 反应 12.0h， 生成 3-{[4-(benzyloxy)phenyl]hydrazono}piperidin-2-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

• 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.
• INDOLE COMPOUND
  申请人：Astellas Pharma Inc.

  公开号：EP3095781B1

  公开（公告）日：2018-10-03
• Optical evodiamine derivatives: Asymmetric synthesis and antitumor activity
  作者：Zhen-Gang Li、Guo-Qiang Dong、Sheng-Zheng Wang、Zhen-Yuan Miao、Jian-Zhong Yao、Wan-Nian Zhang、Chun-Quan Sheng

  DOI：10.1016/j.cclet.2014.11.011

  日期：2015.3

  of evodiamine derivatives 2 and 3 were obtained by straightforward asymmetric total synthesis. Their inhibitory activities toward topoisomerases I and II and their cytotoxicities in cancer cell lines were evaluated. All the four isomers exhibited good to excellent antitumor potency and the (S)-isomers were generally more active than the (R)-isomers. The binding modes of (S)-2 with topoisomerases I and

  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。