(Z)-3-((1H-pyrrol-2-yl)methylene)-1-(2,6-dichlorophenyl)indolin-2-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (Z)-3-((1H-pyrrol-2-yl)methylene)-1-(2,6-dichlorophenyl)indolin-2-one
• 英文别名: (3Z)-1-(2,6-dichlorophenyl)-3-(1H-pyrrol-2-ylmethylidene)indol-2-one
• 化学式: C₁₉H₁₂Cl₂N₂O
• 分子量: 355.223
• InChiKey: DWXAWYBKSOWACH-KAMYIIQDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  36.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  5-氯-2-酰氯噻吩 、 (Z)-3-((1H-pyrrol-2-yl)methylene)-1-(2,6-dichlorophenyl)indolin-2-one 在 sodium hydride 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 以45%的产率得到(Z)-3-((1-(5-chlorothiophene-2-carbonyl)-1H-pyrrol-2-yl)methylene)-1-(2,6-dichlorophenyl)indolin-2-one
  参考文献：
  名称：

  Rational modification of semaxanib and sunitinib for developing a tumor growth inhibitor targeting ATP binding site of tyrosine kinase

  摘要：

  Analysis of the crystal structure of tyrosine kinase in complexation with an ATP analogue, supplemented with the molecular docking studies of semaxanib and sunitinib in the ATP binding site of the enzyme enabled us to make design of a series of tyrosine kinase inhibitors. The combination of pyrrole and indolinone in one molecule and placement of appropriate substituent thereof made the molecule compatible for the hydrophobic sub-pocket of the enzyme. Screening of the compounds over 60 cell line panel of human tumor cell lines identified compound 3a that exhibited GI(50) 35 nM and 63 nM against MCF7 and MDA-MB-468 cell lines of breast cancer. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.11.049
• 作为产物：
  描述：

  2-吡咯甲醛 、 1-(2,6-二氯苯基)-1,3-二氢-2H-吲哚-2-酮 在 哌啶 作用下， 以 氯仿 为溶剂， 反应 1.0h， 以87.2%的产率得到(Z)-3-((1H-pyrrol-2-yl)methylene)-1-(2,6-dichlorophenyl)indolin-2-one
  参考文献：
  名称：

  Rational modification of semaxanib and sunitinib for developing a tumor growth inhibitor targeting ATP binding site of tyrosine kinase

  摘要：

  Analysis of the crystal structure of tyrosine kinase in complexation with an ATP analogue, supplemented with the molecular docking studies of semaxanib and sunitinib in the ATP binding site of the enzyme enabled us to make design of a series of tyrosine kinase inhibitors. The combination of pyrrole and indolinone in one molecule and placement of appropriate substituent thereof made the molecule compatible for the hydrophobic sub-pocket of the enzyme. Screening of the compounds over 60 cell line panel of human tumor cell lines identified compound 3a that exhibited GI(50) 35 nM and 63 nM against MCF7 and MDA-MB-468 cell lines of breast cancer. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.11.049

文献信息

• Rational modification of semaxanib and sunitinib for developing a tumor growth inhibitor targeting ATP binding site of tyrosine kinase
  作者：Jagroop Kaur、Baljit Kaur、Palwinder Singh

  DOI：10.1016/j.bmcl.2017.11.049

  日期：2018.1

  Analysis of the crystal structure of tyrosine kinase in complexation with an ATP analogue, supplemented with the molecular docking studies of semaxanib and sunitinib in the ATP binding site of the enzyme enabled us to make design of a series of tyrosine kinase inhibitors. The combination of pyrrole and indolinone in one molecule and placement of appropriate substituent thereof made the molecule compatible for the hydrophobic sub-pocket of the enzyme. Screening of the compounds over 60 cell line panel of human tumor cell lines identified compound 3a that exhibited GI(50) 35 nM and 63 nM against MCF7 and MDA-MB-468 cell lines of breast cancer. (C) 2017 Elsevier Ltd. All rights reserved.