N-(6-(10H-benzo[b]pyrido[2,3-e][1,4]thiazin-10-yl)hexyl)-O-methylhydroxylamine

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N-(6-(10H-benzo[b]pyrido[2,3-e][1,4]thiazin-10-yl)hexyl)-O-methylhydroxylamine
• 英文别名: N-methoxy-6-pyrido[3,2-b][1,4]benzothiazin-10-ylhexan-1-amine
• 化学式: C₁₈H₂₃N₃OS
• 分子量: 329.466
• InChiKey: DEKITJMQIIOWLZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  23
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  62.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-(6-溴己氧基)四氢吡喃 在 氢溴酸 、 sodium hydride 、 对甲苯磺酸 作用下， 以 甲醇 、 正己烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 30.84h， 生成 N-(6-(10H-benzo[b]pyrido[2,3-e][1,4]thiazin-10-yl)hexyl)-O-methylhydroxylamine
  参考文献：
  名称：

  Novel aminoalkylated azaphenothiazines as potential inhibitors of T98G, H460 and SNU80 cancer cell lines in vitro

  摘要：

  A set of twenty-one novel aminoalkylated azaphenothiazines is synthesized using a two-step methodology starting from azaphenothiazines. The key step was the selective monoalkylation at position 10 of azaphenothiazines. In all, twenty-five molecules, including intermediates, were investigated for their in vitro anticancer activity, of which fourteen azaphenothiazines (2b, 3a, 3c, 3d, 3e-h, 3j, 3n, 3o, 3p, 3s, and 3u) were found to decrease the metabolic viability and growth of the T98G, H460 and SNU80 cancer cells effectively in a dose-dependent manner. In silico, pharmacokinetic studies suggest that these molecules have good bioavailability, water solubility and other drug-like parameters. Compounds 3a, 3c and 3g were identified as the leading molecules for future investigation due to their (a) high activity against T98G brain, H460 lung and SNU80 thyroid cancer cells; (b) low cytotoxicity with regard to non-malignant HEK293 and MRC5 cells; (c) low toxic risk levels based on in vitro and in silico evaluations; (d) good theoretical oral bioavailability according to Lipinski 'rule of five' pharmacokinetic parameters; and (e) better drug-likeness and drug-score values. (C) 2016 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2016.03.056

文献信息

• Novel aminoalkylated azaphenothiazines as potential inhibitors of T98G, H460 and SNU80 cancer cell lines in vitro
  作者：Khushbu Kushwaha、Nagendra Kumar Kaushik、Neha Kaushik、Mahesh Chand、Reena Kaushik、Eun ha Choi、Subhash C. Jain

  DOI：10.1016/j.bmcl.2016.03.056

  日期：2016.5

  A set of twenty-one novel aminoalkylated azaphenothiazines is synthesized using a two-step methodology starting from azaphenothiazines. The key step was the selective monoalkylation at position 10 of azaphenothiazines. In all, twenty-five molecules, including intermediates, were investigated for their in vitro anticancer activity, of which fourteen azaphenothiazines (2b, 3a, 3c, 3d, 3e-h, 3j, 3n, 3o, 3p, 3s, and 3u) were found to decrease the metabolic viability and growth of the T98G, H460 and SNU80 cancer cells effectively in a dose-dependent manner. In silico, pharmacokinetic studies suggest that these molecules have good bioavailability, water solubility and other drug-like parameters. Compounds 3a, 3c and 3g were identified as the leading molecules for future investigation due to their (a) high activity against T98G brain, H460 lung and SNU80 thyroid cancer cells; (b) low cytotoxicity with regard to non-malignant HEK293 and MRC5 cells; (c) low toxic risk levels based on in vitro and in silico evaluations; (d) good theoretical oral bioavailability according to Lipinski 'rule of five' pharmacokinetic parameters; and (e) better drug-likeness and drug-score values. (C) 2016 Published by Elsevier Ltd.