3,4-Bis[1-(2-chloroethyl)indol-3-yl]-1-methylpyrrole-2,5-dione | 436867-08-2

• 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: 3,4-Bis[1-(2-chloroethyl)indol-3-yl]-1-methylpyrrole-2,5-dione
• CAS: 436867-08-2
• 化学式: C₂₅H₂₁Cl₂N₃O₂
• 分子量: 466.367
• InChiKey: CQYSDDNGYUKVHI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  47.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3,4-Bis[1-(2-chloroethyl)indol-3-yl]-1-methylpyrrole-2,5-dione 在 氢氧化钾 、 N,N-二异丙基乙胺 、 potassium iodide 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 生成
  参考文献：
  名称：

  Macrocyclic bisindolylmaleimides as inhibitors of protein kinase C and glycogen synthase kinase-3

  摘要：

  Efficient methods were developed to synthesize a novel series of macrocyclic bisindolylmaleimides containing linkers with multiple heteroatoms. Potent inhibitors (single digit nanomolar IC50) for PKC-beta and GSK-3beta were identified, and compounds showed good selectivity over PKC-alpha, -gamma, delta, -epsilon, and -zeta. Representative compound 5a also had high selectivity in a screening panel of 10 other protein kinases. In cell-based functional assays, several compounds effectively blocked interleukin-8 release induced by PKC-beta11 and increased glycogen synthase activity by inhibiting GSK-3beta. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00644-9
• 作为产物：
  描述：

  吲哚-3-乙醛酸甲酯 在 potassium tert-butylate 、 potassium carbonate 、 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 生成 3,4-Bis[1-(2-chloroethyl)indol-3-yl]-1-methylpyrrole-2,5-dione
  参考文献：
  名称：

  Macrocyclic bisindolylmaleimides as inhibitors of protein kinase C and glycogen synthase kinase-3

  摘要：

  Efficient methods were developed to synthesize a novel series of macrocyclic bisindolylmaleimides containing linkers with multiple heteroatoms. Potent inhibitors (single digit nanomolar IC50) for PKC-beta and GSK-3beta were identified, and compounds showed good selectivity over PKC-alpha, -gamma, delta, -epsilon, and -zeta. Representative compound 5a also had high selectivity in a screening panel of 10 other protein kinases. In cell-based functional assays, several compounds effectively blocked interleukin-8 release induced by PKC-beta11 and increased glycogen synthase activity by inhibiting GSK-3beta. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00644-9

文献信息

• Macrocyclic bisindolylmaleimides as inhibitors of protein kinase C and glycogen synthase kinase-3
  作者：Han-Cheng Zhang、Kimberly B. White、Hong Ye、David F. McComsey、Claudia K. Derian、Michael F. Addo、Patricia Andrade-Gordon、Annette J. Eckardt、Bruce R. Conway、Lori Westover、Jun Z. Xu、Richard Look、Keith T. Demarest、Stuart Emanuel、Bruce E. Maryanoff

  DOI：10.1016/s0960-894x(03)00644-9

  日期：2003.9

  Efficient methods were developed to synthesize a novel series of macrocyclic bisindolylmaleimides containing linkers with multiple heteroatoms. Potent inhibitors (single digit nanomolar IC50) for PKC-beta and GSK-3beta were identified, and compounds showed good selectivity over PKC-alpha, -gamma, delta, -epsilon, and -zeta. Representative compound 5a also had high selectivity in a screening panel of 10 other protein kinases. In cell-based functional assays, several compounds effectively blocked interleukin-8 release induced by PKC-beta11 and increased glycogen synthase activity by inhibiting GSK-3beta. (C) 2003 Elsevier Ltd. All rights reserved.