3,4-Bis[1-(2-hydroxyethyl)indol-3-yl]pyrrole-2,5-dione | 609826-38-2

• 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-hydroxyethyl)indol-3-yl]pyrrole-2,5-dione
• CAS: 609826-38-2
• 化学式: C₂₄H₂₁N₃O₄
• 分子量: 415.448
• InChiKey: IFENDUVGYQNDOK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  96.5
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3,4-Bis[1-(2-hydroxyethyl)indol-3-yl]pyrrole-2,5-dione 在 吡啶 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 12,18-dimethyl-10,11,12,13,14,16,17,18,19,20-decahydro-15-oxa-2,9,12,18,21-pentaaza-1H-diindolo[1,2,3-m,n:3',2',1'-r,s]cyclononadec-14,16,18-trien[16,17-c]-pyrrole-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
• 作为产物：
  描述：

  吲哚-3-乙醛酸甲酯 在 盐酸 、 potassium tert-butylate 、 caesium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 3,4-Bis[1-(2-hydroxyethyl)indol-3-yl]pyrrole-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

• Macroheterocyclic compounds as kinase inhibitors
  申请人：Zhang Han-Cheng

  公开号：US20070088019A1

  公开（公告）日：2007-04-19

  This invention is directed to macroheterocyclic compounds useful as kinase or dual-kinase inhibitors, methods for producing such compounds and methods for treating or ameliorating a kinase or dual-kinase mediated disease, condition or disorder.

  本发明涉及宏环杂环化合物，可用作激酶或双重激酶抑制剂，制备这种化合物的方法以及用于治疗或改善激酶或双重激酶介导的疾病、状况或障碍的方法。
• [EN] MACROHETEROCYLIC COMPOUNDS AS KINASE INHIBITORS<br/>[FR] COMPOSÉS MACROHÉTÉROCYCLIQUES EN TANT QU'INHIBITEURS DE KINASE
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2007041195A2

  公开（公告）日：2007-04-12

  [EN] This invention is directed to macroheterocyclic compounds useful as kinase or dual-kinase inhibitors, methods for producing such compounds and methods for treating or ameliorating a kinase or dual-kinase mediated disease, condition or disorder.
  [FR] La présente invention concerne des composés macrohétérocycliques pouvant être employés en tant qu'inhibiteurs de kinase ou inhibiteurs de double kinase, des méthodes de production de tels composés et des méthodes de traitement ou de soulagement d'une maladie, d'un état pathologique ou d'un trouble faisant intervenir une kinase ou une double kinase.
• 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.