N,N-diethyl-10-((1E,3Z)-4-(2-(4-methoxyphenyl)-2H-tetrazol-5-yl)buta-1,3-dien-1-yl)-10H-phenothiazin-2-amine | 1401710-53-9

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: N,N-diethyl-10-((1E,3Z)-4-(2-(4-methoxyphenyl)-2H-tetrazol-5-yl)buta-1,3-dien-1-yl)-10H-phenothiazin-2-amine
• 英文别名: N,N-diethyl-10-{(1E,3Z)-4-[2-(4-methoxyphenyl)-2H-tetrazol-5-yl]but-1,3-dien-1-yl}-10H-phenothiazin-2-amine
• CAS: 1401710-53-9
• 化学式: C₂₈H₂₈N₆OS
• 分子量: 496.636
• InChiKey: MRZDEPXLVQZQRT-BHTMSSRASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.35
• 重原子数：
  36.0
• 可旋转键数：
  8.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  59.31
• 氢给体数：
  0.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  N,N-diethyl-10-((1E,3Z)-4-(2-(4-methoxyphenyl)-2H-tetrazol-5-yl)buta-1,3-dien-1-yl)-10H-phenothiazin-2-amine 在 dimethyl sulfide borane 、 双氧水 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 48.0h， 以23%的产率得到1-[2-(diethylamino)-10H-phenothiazin-10-yl]-4-[2-(4-methoxyphenyl)-2H-tetrazol-5-yl]butan-2-ol
  参考文献：
  名称：

  Synthesis and pharmacological investigation of new N-hydroxyalkyl-2-aminophenothiazines exhibiting marked MDR inhibitory effect

  摘要：

  Novel N-hydroxyalkyl-2-aminophenothiazines implying a tetrazole moiety at the alkyl chain have been synthesized by hydroboration oxidation of dienes followed by Buchwald Hartwig cross-coupling reaction. Also, some sulfoxide and sulfone derivatives have been prepared by selective oxidations. MDR inhibition studies on rat hepatocyte cell culture revealed that some derivatives exhibit marked biological efficacy exceeding that of the standard verapamil (e.g., 3h, 4h, 16). Selected derivatives were subjected to chemical resolution to provide both enantiomers which were shown of similar activity on P-gp interaction measurements. The new compounds exhibited no toxicity. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.04.034
• 作为产物：
  描述：

  2-chloro-10-((1E,3Z)-4-(2-(4-methoxyphenyl)-2H-tetrazol-5-yl)buta-1,3-dien-1-yl)-10H-phenothiazine 、 二乙胺 在 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 甲苯 为溶剂， 生成 N,N-diethyl-10-((1E,3Z)-4-(2-(4-methoxyphenyl)-2H-tetrazol-5-yl)buta-1,3-dien-1-yl)-10H-phenothiazin-2-amine
  参考文献：
  名称：

  Synthesis and pharmacological investigation of new N-hydroxyalkyl-2-aminophenothiazines exhibiting marked MDR inhibitory effect

  摘要：

  Novel N-hydroxyalkyl-2-aminophenothiazines implying a tetrazole moiety at the alkyl chain have been synthesized by hydroboration oxidation of dienes followed by Buchwald Hartwig cross-coupling reaction. Also, some sulfoxide and sulfone derivatives have been prepared by selective oxidations. MDR inhibition studies on rat hepatocyte cell culture revealed that some derivatives exhibit marked biological efficacy exceeding that of the standard verapamil (e.g., 3h, 4h, 16). Selected derivatives were subjected to chemical resolution to provide both enantiomers which were shown of similar activity on P-gp interaction measurements. The new compounds exhibited no toxicity. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.04.034

文献信息

• A new synthetic approach to phenothiazine-2-amines
  作者：Daniella Takács、Orsolya Egyed、László Drahos、Zsuzsanna Riedl、György Hajós

  DOI：10.1016/j.tetlet.2012.07.083

  日期：2012.10

  Elaboration of a Buchwald-Hartwig protocol for the introduction of amino functions to position 2 of the phenothiazine ring system has opened a new access to various N-alkyl and N-dienyl phenothiazines bearing secondary amines, tertiary amines, and amide moieties. Hydrolysis of the amido derivatives gave unsubstituted phenothiazine-2-amines. This protocol provides an easy access to phenothiazine-2-amines starting from the commercially available starting compounds. (C) 2012 Elsevier Ltd. All rights reserved.