1-(1H'-benz[g]indole-2',3'-dione)-4(4'-methoxyphenyl)-3-semicarbazone | 1155338-46-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 1-(1H'-benz[g]indole-2',3'-dione)-4(4'-methoxyphenyl)-3-semicarbazone
• 英文别名: 1-(4-methoxyphenyl)-3-[(2-oxobenzo[g]indol-3-yl)amino]thiourea
• CAS: 1155338-46-7
• 化学式: C₂₀H₁₆N₄O₂S
• 分子量: 376.439
• InChiKey: DJPUECOLSXMNJH-UHFFFAOYSA-N

物化性质

• 熔点：
  240-268 °C (decomp)
• 密度：
  1.39±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.49
• 重原子数：
  27.0
• 可旋转键数：
  3.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  74.75
• 氢给体数：
  3.0
• 氢受体数：
  4.0

反应信息

• 作为产物：
  描述：

  1H-苯并[g]吲哚-2,3-二酮 、 4-(4-甲氧基苯基)-3-硫代氨基甲酰肼 在 溶剂黄146 作用下， 以 乙醇 为溶剂， 以66%的产率得到1-(1H'-benz[g]indole-2',3'-dione)-4(4'-methoxyphenyl)-3-semicarbazone
  参考文献：
  名称：

  Synthesis, Activity, and Pharmacophore Development for Isatin-β-thiosemicarbazones with Selective Activity toward Multidrug-Resistant Cells

  摘要：

  We have recently identified a new class of compounds that selectively kill cells that express P-glycoprotein (P-gp, MDR1), the ATPase efflux pump that confers multidrug resistance on cancer cells. Several isatin-beta-thiosemicarbazones from our initial study have been validated and a range of analogues synthesized and tested. A number demonstrated improved MDR1-selective activity over the lead, NSC73306 (1). Pharmacophores for cytotoxicity and MDR1 selectivity were generated to delineate the structural features required for activity. The MDR1-selective pharmacophore highlights the importance of aromatic/hydrophobic features at the N4 position of the thiosemicarbazone and the reliance on the isatin moiety as key bioisosteric contributors. Additionally, a quantitative structure-activity relationship (QSAR) model that yielded a cross-validated correlation coefficient of 0.85 effectively predicts the cytotoxicity of untested thiosemicarbazones. Together, the models serve as effective approaches for predicting structures with MDR1-selective activity and aid in directing the search for the mechanism of action of 1.

  DOI：

  10.1021/jm800861c

文献信息

• [EN] THIOSEMICARBAZONES WITH MDR1 - INVERSE ACTIVITY<br/>[FR] THIOSEMICARBAZONES À ACTIVITÉ ANTI-MDR1
  申请人：US HEALTH

  公开号：WO2012033601A1

  公开（公告）日：2012-03-15

  Disclosed herein are drug compounds that have MDR-inverse activity and thus are effective against multidrug-resistant cells. Exemplary compounds disclosed herein have the structure;Formula (I). Examples of the disclosed compounds have been found to have, inter alia, efficacy in directly treating multidrug resistant cells, rendering multidrug resistant cells susceptible to other chemotherapeutics and in some instances reversing multidrug resistance.

  本文披露了具有MDR逆转活性的药物化合物，因此对多药耐药细胞有效。本文披露的示例化合物具有下列结构；公式（I）。已发现披露的化合物的示例具有直接治疗多药耐药细胞的功效，使多药耐药细胞对其他化疗药物敏感，并在某些情况下逆转多药耐药。
• COMPOUNDS WITH MDR1-INVERSE ACTIVITY
  申请人：Hall Matthew D.

  公开号：US20100316655A1

  公开（公告）日：2010-12-16

  Disclosed herein are drug compounds that have MDR-inverse activity and thus are effective against multidrug-resistant cells. Exemplary compounds disclosed herein have the structure: Examples of the disclosed compounds have been found to have, inter alia, efficacy in directly treating multidrug resistant cells, rendering multidrug resistant cells susceptible to other chemotherapeutics and in some instances reversing multidrug resistance.
• [EN] COMPOUNDS WITH MDR1-INVERSE ACTIVITY<br/>[FR] COMPOSÉS À ACTIVITÉ MDR1 INVERSE
  申请人：US GOV HEALTH & HUMAN SERV

  公开号：WO2009102433A2

  公开（公告）日：2009-08-20

  Disclosed herein are drug compounds that have MDR-inverse activity and thus are effective against multidrug-resistant cells. Exemplary compounds disclosed herein have the following structure: (I). Examples of the disclosed compounds have been found to have, inter alia, efficacy in directly treating multidrug resistant cells, rendering multidrug resistant cells susceptible to other chemotherapeutics and in some instances reversing multidrug resistance.
• Synthesis, Activity, and Pharmacophore Development for Isatin-β-thiosemicarbazones with Selective Activity toward Multidrug-Resistant Cells
  作者：Matthew D. Hall、Noeris K. Salam、Jennifer L. Hellawell、Henry M. Fales、Caroline B. Kensler、Joseph A. Ludwig、Gergely Szakács、David E. Hibbs、Michael M. Gottesman

  DOI：10.1021/jm800861c

  日期：2009.5.28

  We have recently identified a new class of compounds that selectively kill cells that express P-glycoprotein (P-gp, MDR1), the ATPase efflux pump that confers multidrug resistance on cancer cells. Several isatin-beta-thiosemicarbazones from our initial study have been validated and a range of analogues synthesized and tested. A number demonstrated improved MDR1-selective activity over the lead, NSC73306 (1). Pharmacophores for cytotoxicity and MDR1 selectivity were generated to delineate the structural features required for activity. The MDR1-selective pharmacophore highlights the importance of aromatic/hydrophobic features at the N4 position of the thiosemicarbazone and the reliance on the isatin moiety as key bioisosteric contributors. Additionally, a quantitative structure-activity relationship (QSAR) model that yielded a cross-validated correlation coefficient of 0.85 effectively predicts the cytotoxicity of untested thiosemicarbazones. Together, the models serve as effective approaches for predicting structures with MDR1-selective activity and aid in directing the search for the mechanism of action of 1.