(2Z)-4-{1-[(2-chloro-10H-phenothiazin-10-yl)methyl]-3-[2-(4-methoxyphenyl)-2H-tetrazol-5-yl]propoxy}-4-oxobut-2-enoic acid | 1442372-03-3

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: (2Z)-4-{1-[(2-chloro-10H-phenothiazin-10-yl)methyl]-3-[2-(4-methoxyphenyl)-2H-tetrazol-5-yl]propoxy}-4-oxobut-2-enoic acid
• CAS: 1442372-03-3
• 化学式: C₂₈H₂₄ClN₅O₅S
• 分子量: 578.048
• InChiKey: OXGKUWKXXWIZOG-PFONDFGASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.11
• 重原子数：
  40.0
• 可旋转键数：
  10.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  119.67
• 氢给体数：
  1.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  (2Z)-4-{1-[(2-chloro-10H-phenothiazin-10-yl)methyl]-3-[2-(4-methoxyphenyl)-2H-tetrazol-5-yl]propoxy}-4-oxobut-2-enoic acid 在 咪唑 、 tris-(dibenzylideneacetone)dipalladium(0) 、 水 、 sodium hydroxide 、 sodium t-butanolate 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 100.0h， 生成 10-(2-{[tert-butyl(diphenyl)silyl]oxy}-4-[2-(4-methoxyphenyl)-2H-tetrazol-5-yl]butyl)-2-morpholin-4-yl-10H-phenothiazine
  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：

  4-((1-(2-chloro-10H-phenothiazin-10-yl)-4-(2-(4-methoxyphenyl)-2H-tetrazol-5-yl)butan-2-yl)oxy)-4-oxobut-2-enoic acid (S)-1-phenylethylamine salt 在 盐酸 作用下， 以 水 、 乙酸乙酯 为溶剂， 反应 0.83h， 生成 (2Z)-4-{1-[(2-chloro-10H-phenothiazin-10-yl)methyl]-3-[2-(4-methoxyphenyl)-2H-tetrazol-5-yl]propoxy}-4-oxobut-2-enoic acid
  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