(10E)-6-(3,4-dimethoxyphenyl)-10-[(3,4-dimethoxyphenyl)methylidene]-5,7,8,9-tetrahydrobenzo[b][1,4]benzodiazepine | 1575837-56-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二芳基庚烷
• 英文名称: (10E)-6-(3,4-dimethoxyphenyl)-10-[(3,4-dimethoxyphenyl)methylidene]-5,7,8,9-tetrahydrobenzo[b][1,4]benzodiazepine
• CAS: 1575837-56-7
• 化学式: C₃₀H₃₀N₂O₄
• 分子量: 482.579
• InChiKey: CLRPNTXFCKJDDX-CAPFRKAQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  36
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  61.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  环己酮 在 sodium hydroxide 作用下， 以 乙醇 、 溶剂黄146 为溶剂， 反应 20.0h， 生成 (10E)-6-(3,4-dimethoxyphenyl)-10-[(3,4-dimethoxyphenyl)methylidene]-5,7,8,9-tetrahydrobenzo[b][1,4]benzodiazepine
  参考文献：
  名称：

  Nonclassical antifolates, part 5. Benzodiazepine analogs as a new class of DHFR inhibitors: Synthesis, antitumor testing and molecular modeling study

  摘要：

  A new series of tetrahydro-quinazoline and tetrahydro-1H-dibenzo[b,e][1,4]diazepine analogs were synthesized and tested for their DHFR inhibition and in vitro antitumor activity. Compound 35 showed a remarkable DHFR inhibitory potency (IC50, 0.004 mu M) which is twenty fold more active than methotrexate (MIX). Compounds 17 and 23 proved to be fifteen fold more active than the known antitumor 5-FU, with MG-MID GI(50), TGI, and LC50 values of 1.5, 46.8, 93.3 and 1.4, 17.4, 93.3 mu M, respectively. Computer modeling studies allowed the identification that methoxy and methyl substituents, the pi-system of the chalcone core, the nitrogen atoms, on the dibenzodiazepine ring as pharmacophoric features essential for activity. These mark points could be used as template model for further future optimization. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.01.004

文献信息

• Nonclassical antifolates, part 5. Benzodiazepine analogs as a new class of DHFR inhibitors: Synthesis, antitumor testing and molecular modeling study
  作者：Hussein I. El-Subbagh、Ghada S. Hassan、Shahenda M. El-Messery、Sarah T. Al-Rashood、Fatmah A.M. Al-Omary、Yasmin S. Abulfadl、Marwa I. Shabayek

  DOI：10.1016/j.ejmech.2014.01.004

  日期：2014.3

  A new series of tetrahydro-quinazoline and tetrahydro-1H-dibenzo[b,e][1,4]diazepine analogs were synthesized and tested for their DHFR inhibition and in vitro antitumor activity. Compound 35 showed a remarkable DHFR inhibitory potency (IC50, 0.004 mu M) which is twenty fold more active than methotrexate (MIX). Compounds 17 and 23 proved to be fifteen fold more active than the known antitumor 5-FU, with MG-MID GI(50), TGI, and LC50 values of 1.5, 46.8, 93.3 and 1.4, 17.4, 93.3 mu M, respectively. Computer modeling studies allowed the identification that methoxy and methyl substituents, the pi-system of the chalcone core, the nitrogen atoms, on the dibenzodiazepine ring as pharmacophoric features essential for activity. These mark points could be used as template model for further future optimization. (C) 2014 Elsevier Masson SAS. All rights reserved.