2-chloro-10-((1E,3Z)-4-(2-(4-methoxyphenyl)-2H-tetrazol-5-yl)buta-1,3-dien-1-yl)-10H-phenothiazine | 742105-63-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻嗪类
• 英文名称: 2-chloro-10-((1E,3Z)-4-(2-(4-methoxyphenyl)-2H-tetrazol-5-yl)buta-1,3-dien-1-yl)-10H-phenothiazine
• 英文别名: 2-chloro-10-[(1E,3Z)-4-[2-(4-methoxyphenyl)tetrazol-5-yl]buta-1,3-dienyl]phenothiazine
• CAS: 742105-63-1
• 化学式: C₂₄H₁₈ClN₅OS
• 分子量: 459.959
• InChiKey: QIMYZSJQTZNUAQ-HRKCWBCCSA-N

物化性质

• 熔点：
  114-116 °C
• 沸点：
  643.6±65.0 °C(Predicted)
• 密度：
  1.34±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.9
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  81.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-chloro-10-((1E,3Z)-4-(2-(4-methoxyphenyl)-2H-tetrazol-5-yl)buta-1,3-dien-1-yl)-10H-phenothiazine 在 dimethyl sulfide borane 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 以46%的产率得到6-((2-chloro-10H-phenothiazin-10-yl)methyl)-2-(4-methoxyphenyl)-5,6,7,8-tetrahydro-2H-tetrazolo[5,1-f][1,2]azaborinin-4-ium-5-uide
  参考文献：
  名称：

  Selective hydroboration of dieneamines. Formation of hydroxyalkylphenothiazines as MDR modulators

  摘要：

  N-dienylphenothiazines synthesized from tetrazolo[1,5-a]pyridinium salts by treatment with phenothiazine were subjected to catalytic hydrogenation to yield N-butylphenothiazines, whereas transformation of these dienes with borane dimethyl sulfide (BH3 x Me2S) resulted in selective hydroboration of one double bond and full reduction of the other double bond to give 2-hydroxybutylphenothiazines. Position of the hydroxyl group was supported by NMR spectroscopy and verified by X-ray analysis. Comparison of MDR modulatory activity of the new derivatives revealed that the hydroxybutyl compounds are promising candidates for development of novel MDR inhibitors. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.05.065
• 作为产物：
  描述：

  2-氯吩噻嗪 、 3-(4-methoxyphenyl)-tetrazolo[1,5-a]pyridin-4-ium tetrafluoroborate 在 sodium hydride 作用下， 以 四氢呋喃 、 mineral oil 为溶剂， 反应 48.33h， 以59%的产率得到2-chloro-10-((1E,3Z)-4-(2-(4-methoxyphenyl)-2H-tetrazol-5-yl)buta-1,3-dien-1-yl)-10H-phenothiazine
  参考文献：
  名称：

  Selective hydroboration of dieneamines. Formation of hydroxyalkylphenothiazines as MDR modulators

  摘要：

  N-dienylphenothiazines synthesized from tetrazolo[1,5-a]pyridinium salts by treatment with phenothiazine were subjected to catalytic hydrogenation to yield N-butylphenothiazines, whereas transformation of these dienes with borane dimethyl sulfide (BH3 x Me2S) resulted in selective hydroboration of one double bond and full reduction of the other double bond to give 2-hydroxybutylphenothiazines. Position of the hydroxyl group was supported by NMR spectroscopy and verified by X-ray analysis. Comparison of MDR modulatory activity of the new derivatives revealed that the hydroxybutyl compounds are promising candidates for development of novel MDR inhibitors. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.05.065

文献信息

• Synthesis and pharmacological investigation of new N-hydroxyalkyl-2-aminophenothiazines exhibiting marked MDR inhibitory effect
  作者：Daniella Takács、Orsolya Egyed、László Drahos、Pál Szabó、Katalin Jemnitz、Mónika Szabó、Zsuzsa Veres、Júlia Visy、József Molnár、Zsuzsanna Riedl、György Hajós

  DOI：10.1016/j.bmc.2013.04.034

  日期：2013.7

  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.
• 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.
• Selective hydroboration of dieneamines. Formation of hydroxyalkylphenothiazines as MDR modulators
  作者：Daniella Takács、Ildikó Nagy、Petra Bombicz、Orsolya Egyed、Katalin Jemnitz、Zsuzsanna Riedl、József Molnár、Leonard Amaral、György Hajós

  DOI：10.1016/j.bmc.2012.05.065

  日期：2012.7

  N-dienylphenothiazines synthesized from tetrazolo[1,5-a]pyridinium salts by treatment with phenothiazine were subjected to catalytic hydrogenation to yield N-butylphenothiazines, whereas transformation of these dienes with borane dimethyl sulfide (BH3 x Me2S) resulted in selective hydroboration of one double bond and full reduction of the other double bond to give 2-hydroxybutylphenothiazines. Position of the hydroxyl group was supported by NMR spectroscopy and verified by X-ray analysis. Comparison of MDR modulatory activity of the new derivatives revealed that the hydroxybutyl compounds are promising candidates for development of novel MDR inhibitors. (C) 2012 Elsevier Ltd. All rights reserved.