3-(6-amino-1-methyl-3-indolyl)-4-(1-methyl-3-indolyl)-1H-pyrrole-2,5-dione | 125314-12-7

• 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-(6-amino-1-methyl-3-indolyl)-4-(1-methyl-3-indolyl)-1H-pyrrole-2,5-dione
• 英文别名: Bisindolylmaleimide deriv. 42；3-(6-amino-1-methylindol-3-yl)-4-(1-methylindol-3-yl)pyrrole-2,5-dione
• CAS: 125314-12-7
• 化学式: C₂₂H₁₈N₄O₂
• 分子量: 370.411
• InChiKey: KTAUCQCZXBJXPD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  28
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  82
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  乙酸酐 、 3-(6-amino-1-methyl-3-indolyl)-4-(1-methyl-3-indolyl)-1H-pyrrole-2,5-dione 反应 2.0h， 生成 3-(6-acetamido-1-methyl-3-indolyl)-4-(1-methyl-3-indolyl)-1H-pyrrole-2,5-dione
  参考文献：
  名称：

  Inhibitors of protein kinase C. 1. 2,3-bisarylmaleimides

  摘要：

  The design and synthesis of a series of novel inhibitors of protein kinase C (PKC) is described. These 2,3-bisarylznaleimides were derived from the structural lead provided by the indolocarbazoles, staurosporine and K252a. Optimum activity required the imide NH, both carbonyl groups, and the olefinic bond of the maleimide ring. 2,3-Bisindolylmaleimides were the most active, and the potency of these was improved by a chloro substituent at the 5-position of one indole ring (compound 28, IC50 0.11-mu-M). In a series of (phenylindolyl)maleimides, nitro compound 74 was most active (IC50 0.67-mu-M). Naphthalene 19 and benzothiophene 21 showed greater than 100-fold selectivity for inhibition of PKC over the closely related cAMP-dependent protein kinase (PKA).

  DOI：

  10.1021/jm00079a024
• 作为产物：
  描述：

  6-硝基吲哚 在 palladium on activated charcoal ammonium hydroxide 、 氢气 、 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 140.0 ℃ 、101.33 kPa 条件下， 反应 56.5h， 生成 3-(6-amino-1-methyl-3-indolyl)-4-(1-methyl-3-indolyl)-1H-pyrrole-2,5-dione
  参考文献：
  名称：

  Inhibitors of protein kinase C. 1. 2,3-bisarylmaleimides

  摘要：

  The design and synthesis of a series of novel inhibitors of protein kinase C (PKC) is described. These 2,3-bisarylznaleimides were derived from the structural lead provided by the indolocarbazoles, staurosporine and K252a. Optimum activity required the imide NH, both carbonyl groups, and the olefinic bond of the maleimide ring. 2,3-Bisindolylmaleimides were the most active, and the potency of these was improved by a chloro substituent at the 5-position of one indole ring (compound 28, IC50 0.11-mu-M). In a series of (phenylindolyl)maleimides, nitro compound 74 was most active (IC50 0.67-mu-M). Naphthalene 19 and benzothiophene 21 showed greater than 100-fold selectivity for inhibition of PKC over the closely related cAMP-dependent protein kinase (PKA).

  DOI：

  10.1021/jm00079a024

文献信息

• Substituierte Pyrrole
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0328026A1

  公开（公告）日：1989-08-16

  Pyrrole der allgemeinen Formel worin R¹, R², R³, R⁴, R⁵, R⁶, R⁷, X und Y die in der Beschreibung angegebene Bedeutung haben sind verwendbar bei der Behandlung oder Prophylaxe von inflammatorischen, immunologischen, bronchopulmonären oder cardiovaskulären Krankheiten. Sie werden ausgehend von entsprechend substituierten Furanen oder von auf andere Weise substituierten Pyrrolen hergestellt.

  通式如下的吡咯 其中 R¹、R²、R³、R⁴、R⁵、R⁶、R⁷、X 和 Y 具有说明中给出的含义，可用于治疗或预防炎症、免疫学、支气管肺病或心血管疾病。 它们由适当取代的呋喃或其他取代的吡咯制备而成。
• Polymer conjugates of protein kinase C inhibitors
  申请人：Shearwater Corporation

  公开号：US20030143185A1

  公开（公告）日：2003-07-31

  The invention provides polymer conjugates of protein kinase C (PKC) inhibitors comprising a polymer, such as poly(ethylene glycol), covalently attached to a PKC inhibitor, such as a bisindolylmaleimide molecule. The linkage between the polymer and the PKC inhibitor is preferably hydrolytically degradable. The invention also includes a pharmaceutical composition comprising a polymer conjugate of a PKC inhibitor and a method of treating any condition responsive to a PKC inhibitor by administering a polymer conjugate of the invention.

  本发明提供了蛋白激酶 C (PKC) 抑制剂的聚合物共轭物，该共轭物由聚合物（如聚乙二醇）与 PKC 抑制剂（如双吲哚马来酰亚胺分子）共价连接而成。聚合物与 PKC 抑制剂之间的连接最好是可水解降解的。本发明还包括一种药物组合物，其中包含一种 PKC 抑制剂的聚合物共轭物，以及一种通过施用本发明的聚合物共轭物来治疗对 PKC 抑制剂有反应的任何病症的方法。
• POLYMER CONJUGATES OF PROTEIN KINASE C INHIBITORS
  申请人：Nektar Therapeutics Al, Corporation

  公开号：EP1441772A2

  公开（公告）日：2004-08-04
• US5057614A
  申请人：——

  公开号：US5057614A

  公开（公告）日：1991-10-15
• USRE36736E
  申请人：——

  公开号：USRE36736E

  公开（公告）日：2000-06-13