3-(Naphthalen-2-yloxymethyl)-phenylamine | 772318-54-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 3-(Naphthalen-2-yloxymethyl)-phenylamine
• 英文别名: 3-(Naphthalen-2-yloxymethyl)aniline
• CAS: 772318-54-4
• 化学式: C₁₇H₁₅NO
• 分子量: 249.312
• InChiKey: BFMAZORNZJDALM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  35.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-(Naphthalen-2-yloxymethyl)-phenylamine 在 potassium tert-butylate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.5h， 生成 2-((4,6-dimethylpyrimidin-2-yl)thio)-N-(3-((naphthalen-2-yloxy)methyl)phenyl)acetamide
  参考文献：
  名称：

  Discovery of 2-((4,6-dimethylpyrimidin-2-yl)thio)- N -phenylacetamide derivatives as new potent and selective human sirtuin 2 inhibitors

  摘要：

  Human sirtuin 2 (SIRT2) plays pivotal roles in multiple biological processes such as cell cycle regulation, autophagy, immune and inflammatory responses. Dysregulation of SIRT2 was considered as a main aspect contributing to several human diseases, including cancer. Development of new potent and selective SIRT2 inhibitors is currently desirable, which may provide a new strategy for treatment of related diseases. Herein, a structure-based optimization approach led to new 2-((4,6-dimethylpyrimidin-2-yl) thio)-N-phenylacetamide derivatives as SIRT2 inhibitors. SAR analyses with new synthesized derivatives revealed a number of new potent SIRT2 inhibitors, among which 28e is the most potent inhibitor with an IC50 value of 42 nM. The selectivity analyses found that 28e has a very good selectivity to SIRT2 over SIRT1 and SIRT3. In cellular assays, 28e showed a potent ability to inhibit human breast cancer cell line MCF-7 and increase the acetylation of alpha-tubulin in a dose-dependent manner. This study will aid further efforts to develop highly potent and selective SIRT2 inhibitors for the treatment of cancer and other related diseases. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.04.010
• 作为产物：
  描述：

  3-硝基溴苄 在 盐酸 、 铁粉 、 sodium carbonate 、 caesium carbonate 、 potassium iodide 作用下， 以 乙醇 、 丙酮 为溶剂， 反应 72.0h， 生成 3-(Naphthalen-2-yloxymethyl)-phenylamine
  参考文献：
  名称：

  [[[（萘甲氧基甲氧基）-和[[（喹啉基甲氧基）苯基]氨基]氧代链烷酸酯的合成。一系列新的白三烯D4拮抗剂和5-脂氧合酶抑制剂。

  摘要：

  已经制备了一系列新型的[[（（萘基甲氧基）-和[[（喹啉基甲氧基）苯基]氨基]氧代链烷酸酯。在体外测试了这些化合物作为大鼠多形核白细胞（PMN）5-脂氧合酶（LO）的抑制剂以及卵白蛋白（OA）和白三烯D4（LTD4）诱导的豚鼠（GP）支气管痉挛的抑制剂。GP中许多萘化合物是5-LO的有效抑制剂，而一些喹啉基化合物是LTD4介导的支气管痉挛的有效抑制剂。最有效的萘化合物4-[[[3-（2-萘甲氧基甲氧基）苯基]羟基氨基] -4-氧代丁酸甲酯（6v）在5-LO分析中的IC50为0.6 microM。体内最有效的化合物4-[[[3-（2-喹啉基甲氧基）苯基]羟基氨基] -4-氧代丁酸甲酯（6e）的ED50为3.3 mg / kg，为27。分别针对LTD4-和OA引起的支气管痉挛分别为4 mg / kg（十二指肠内）。当作为LTD4诱导的分离GP气管螺旋带收缩的拮抗剂进行测试时，显示6e是竞争性抑制剂，pKB值为5

  DOI：

  10.1021/jm00158a019

文献信息

• Discovery of 2-((4,6-dimethylpyrimidin-2-yl)thio)- N -phenylacetamide derivatives as new potent and selective human sirtuin 2 inhibitors
  作者：Lingling Yang、Xiaobo Ma、Chen Yuan、Yanying He、Ling Li、Sha Fang、Wei Xia、Tao He、Shan Qian、Zhihong Xu、Guobo Li、Zhouyu Wang

  DOI：10.1016/j.ejmech.2017.04.010

  日期：2017.7

  Human sirtuin 2 (SIRT2) plays pivotal roles in multiple biological processes such as cell cycle regulation, autophagy, immune and inflammatory responses. Dysregulation of SIRT2 was considered as a main aspect contributing to several human diseases, including cancer. Development of new potent and selective SIRT2 inhibitors is currently desirable, which may provide a new strategy for treatment of related diseases. Herein, a structure-based optimization approach led to new 2-((4,6-dimethylpyrimidin-2-yl) thio)-N-phenylacetamide derivatives as SIRT2 inhibitors. SAR analyses with new synthesized derivatives revealed a number of new potent SIRT2 inhibitors, among which 28e is the most potent inhibitor with an IC50 value of 42 nM. The selectivity analyses found that 28e has a very good selectivity to SIRT2 over SIRT1 and SIRT3. In cellular assays, 28e showed a potent ability to inhibit human breast cancer cell line MCF-7 and increase the acetylation of alpha-tubulin in a dose-dependent manner. This study will aid further efforts to develop highly potent and selective SIRT2 inhibitors for the treatment of cancer and other related diseases. (C) 2017 Elsevier Masson SAS. All rights reserved.
• Synthesis of [[(naphthalenylmethoxy)- and -(quinolinylmethoxy)phenyl]amino]oxoalkanoic acid esters. A novel series of leukotriene D4 antagonists and 5-lipoxygenase inhibitors
  作者：John H. Musser、Dennis M. Kubrak、Joseph Chang、Alan J. Lewis

  DOI：10.1021/jm00158a019

  日期：1986.8

  A series of novel [[(naphthalenylmethoxy)- and [[(quinolinylmethoxy)phenyl]amino]oxoalkanoic acid esters have been prepared. These compounds were tested as inhibitors of rat polymorphonuclear leukocyte (PMN) 5-lipoxygenase (LO) in vitro and as inhibitors of ovalbumin (OA) and leukotriene D4 (LTD4) induced bronchospasm in the guinea pig (GP) in vivo. Many naphthalenyl compounds were potent inhibitors

  已经制备了一系列新型的[[（（萘基甲氧基）-和[[（喹啉基甲氧基）苯基]氨基]氧代链烷酸酯。在体外测试了这些化合物作为大鼠多形核白细胞（PMN）5-脂氧合酶（LO）的抑制剂以及卵白蛋白（OA）和白三烯D4（LTD4）诱导的豚鼠（GP）支气管痉挛的抑制剂。GP中许多萘化合物是5-LO的有效抑制剂，而一些喹啉基化合物是LTD4介导的支气管痉挛的有效抑制剂。最有效的萘化合物4-[[[3-（2-萘甲氧基甲氧基）苯基]羟基氨基] -4-氧代丁酸甲酯（6v）在5-LO分析中的IC50为0.6 microM。体内最有效的化合物4-[[[3-（2-喹啉基甲氧基）苯基]羟基氨基] -4-氧代丁酸甲酯（6e）的ED50为3.3 mg / kg，为27。分别针对LTD4-和OA引起的支气管痉挛分别为4 mg / kg（十二指肠内）。当作为LTD4诱导的分离GP气管螺旋带收缩的拮抗剂进行测试时，显示6e是竞争性抑制剂，pKB值为5