N-Desmethylsotrastaurin

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: N-Desmethylsotrastaurin
• 英文别名: 3-(1H-indol-3-yl)-4-[2-(piperazin-1-yl)-quinazolin-4-yl]-1H-pyrrole-2,5-dione；3-(1H-indol-3-yl)-4-(2-piperazin-1-yl-quinazolin-4-yl)pyrrole-2,5-dione；3-(1H-indol-3-yl)-4-[2-(piperazin-1-yl)-quinazolin-4-yl]-pyrrole-2,5-dione；3-(1H-indol-3-yl)-4-(2-piperazin-1-ylquinazolin-4-yl)pyrrole-2,5-dione
• 化学式: C₂₄H₂₀N₆O₂
• 分子量: 424.462
• InChiKey: WAKGEHXTOOFEAE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  32
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  103
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2,4-喹唑啉二酮 在 potassium tert-butylate 、 sodium hydride 、 N,N-二甲基苯胺 、 三氯氧磷 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 mineral oil 为溶剂， 反应 4.0h， 生成 N-Desmethylsotrastaurin
  参考文献：
  名称：

  Structure–Activity Relationship and Pharmacokinetic Studies of Sotrastaurin (AEB071), a Promising Novel Medicine for Prevention of Graft Rejection and Treatment of Psoriasis

  摘要：

  Protein kinase C (PKC) isotypes have emerged as key targets for the blockade of early T-cell activation. Herein, we report on the structure - activity relationship and the detailed physicochemical and in vivo pharmacokinetic properties of sotrastaurin (AEB071, 1), a novel maleimide-based PKC inhibitor currently in phase II clinical trials. Most notably, the preferred uptake of sotrastaurin into lymphoid tissues is an important feature, which is likely to contribute to its in vivo efficacy.

  DOI：

  10.1021/jm200469u

文献信息

• Crystalline forms of PKC alpha kinase, methods of making such crystals, and uses thereof
  申请人：Novartis AG

  公开号：EP1911838A1

  公开（公告）日：2008-04-16

  The present invention relates generally to the crystalline forms of liganded or unliganded human PKC alpha kinase, the methods of making such crystals and their use in drug discovery. The invention more specifically relates to the use of the three-dimensional structure of the PKC alpha kinase for designing and/or identifying ligands which inhibit the biological function of PKC alpha kinase.

  本发明一般涉及有配体或无配体人 PKC alpha 激酶的结晶形式、制造这种结晶的方法及其在药物发现中的用途。本发明更具体地涉及利用 PKC α 激酶的三维结构设计和/或鉴定抑制 PKC α 激酶生物功能的配体。
• PHARMACEUTICAL COMPOSITION COMPRISING AN INDOLYLMALEIMIDE DERIVATIVE
  申请人：Novartis AG

  公开号：EP1855667A1

  公开（公告）日：2007-11-21
• PHARMACEUTICAL COMBINATION COMPOSITION COMPRISING AT LEAST ONE PKC INHIBITOR AND AT LEAST ONE JAK3 KINASE INHIBITOR FOR TREATING AUTOIMMUNE DISORDERS
  申请人：NOVARTIS AG

  公开号：EP2004178A1

  公开（公告）日：2008-12-24
• USE OF PKC INHIBITORS IN PARTICULAR INDOLYLMALEIMIDE DERIVATIVES IN OCULAR DISEASES
  申请人：NOVARTIS AG

  公开号：EP2056831A2

  公开（公告）日：2009-05-13
• PKC INHIBITORS FOR THE TREATMENT OF B-CELL LYMPHOMA HAVING CHRONIC ACTIVE B-CELL-RECEPTOR SIGNALLING
  申请人：Novartis AG

  公开号：EP2552428A1

  公开（公告）日：2013-02-06