N-(3-(diethylamino)propyl)-4-nitrobenzamide | 114636-51-0

• 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: N-(3-(diethylamino)propyl)-4-nitrobenzamide
• 英文别名: 4-nitro-benzoic acid-(3-diethylamino-propylamide)；4-Nitro-benzoesaeure-(3-diaethylamino-propylamid)；N-[3-(diethylamino)propyl]-4-nitrobenzamide
• CAS: 114636-51-0
• 化学式: C₁₄H₂₁N₃O₃
• 分子量: 279.339
• InChiKey: TXZKCMRBJMQJTJ-UHFFFAOYSA-N

物化性质

• 沸点：
  452.5±30.0 °C(predicted)
• 密度：
  1.126±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  20
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  78.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(3-(diethylamino)propyl)-4-nitrobenzamide 在 吡啶 、 铁粉 、 碳酸氢钠 、 氯化铵 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 12.5h， 生成
  参考文献：
  名称：

  Combining structure- and property-based optimization to identify selective FLT3-ITD inhibitors with good antitumor efficacy in AML cell inoculated mouse xenograft model

  摘要：

  FLT3 mutation is among the most common genetic mutations in acute myeloid leukemia (AML), which is also related with poor overall survival and refractory in AML patients. Recently, FLT3 inhibitors have been approved for AML therapy. Herein, a series of new compounds with pyrazole amine scaffold was discovered, which showed potent inhibitory activity against FLT3-ITD and significant selectivity against both FLT3-ITD and AML cells expressing FLT3-ITD. Compound 46, possessing the most promising cellular activity, blocked the autophosphorylation of FLT3 pathway in MV4-11 cell line. Furthermore, the apoptosis and downregulation of P-STAT5 were also observed in tumor cells extracted from the MV411 cell xenografts model upon compound 46 treatment. Compound 46 was also metabolically stable in vitro and suppressed tumor growth significantly in MV4-11 xenografts model in vivo. Compound 46 showed no toxicity to the viscera of mice and caused no decrease in body weight of mice. In conclusion, the results of this study could provide valuable insights into discovery of new FLT3 inhibitors, and compound 46 was worthy of further development as potential drug candidate to treat AML (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.05.021
• 作为产物：
  描述：

  3-二乙氨基丙腈 在 氨 、 镍 、 苯 作用下， 115.0 ℃ 、9.81 MPa 条件下， 生成 N-(3-(diethylamino)propyl)-4-nitrobenzamide
  参考文献：
  名称：

  Nasarow; Kasarjan, Zhurnal Obshchei Khimii, 1957, vol. 27, p. 3302,3306; engl. Ausg. S. 3336, 3339

  摘要：

  DOI：

文献信息

• N-(Dialkylaminoalkyl)-amides
  作者：R. O. Clinton、U. J. Salvador、S. C. Laskowski

  DOI：10.1021/ja01179a507

  日期：1949.11.19
• Najer; Joannic, Annales Pharmaceutiques Francaises, 1955, vol. 13, p. 556,558
  作者：Najer、Joannic

  DOI：——

  日期：——
• US6207809B1
  申请人：——

  公开号：US6207809B1

  公开（公告）日：2001-03-27
• Nasarow; Kasarjan, Zhurnal Obshchei Khimii, 1957, vol. 27, p. 3302,3306; engl. Ausg. S. 3336, 3339
  作者：Nasarow、Kasarjan

  DOI：——

  日期：——
• Combining structure- and property-based optimization to identify selective FLT3-ITD inhibitors with good antitumor efficacy in AML cell inoculated mouse xenograft model
  作者：Hao Heng、Zhijie Wang、Hongmei Li、Yatian Huang、Qingyuan Lan、Xiaoxing Guo、Liang Zhang、Yanle Zhi、Jiongheng Cai、Tianren Qin、Li Xiang、Shuxian Wang、Yadong Chen、Tao Lu、Shuai Lu

  DOI：10.1016/j.ejmech.2019.05.021

  日期：2019.8

  FLT3 mutation is among the most common genetic mutations in acute myeloid leukemia (AML), which is also related with poor overall survival and refractory in AML patients. Recently, FLT3 inhibitors have been approved for AML therapy. Herein, a series of new compounds with pyrazole amine scaffold was discovered, which showed potent inhibitory activity against FLT3-ITD and significant selectivity against both FLT3-ITD and AML cells expressing FLT3-ITD. Compound 46, possessing the most promising cellular activity, blocked the autophosphorylation of FLT3 pathway in MV4-11 cell line. Furthermore, the apoptosis and downregulation of P-STAT5 were also observed in tumor cells extracted from the MV411 cell xenografts model upon compound 46 treatment. Compound 46 was also metabolically stable in vitro and suppressed tumor growth significantly in MV4-11 xenografts model in vivo. Compound 46 showed no toxicity to the viscera of mice and caused no decrease in body weight of mice. In conclusion, the results of this study could provide valuable insights into discovery of new FLT3 inhibitors, and compound 46 was worthy of further development as potential drug candidate to treat AML (C) 2019 Elsevier Masson SAS. All rights reserved.