3-(7-chloro-1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)-quinazolin-4-yl]pyrrole-2,5-dione | 425638-05-7

• 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: 3-(7-chloro-1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)-quinazolin-4-yl]pyrrole-2,5-dione
• 英文别名: 3-(7-chloro-1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione
• CAS: 425638-05-7
• 化学式: C₂₅H₂₁ClN₆O₂
• 分子量: 472.934
• InChiKey: AQGHYUYFBXMRBC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  34
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  94.2
• 氢给体数：
  2
• 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 4.75h， 生成 3-(7-chloro-1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)-quinazolin-4-yl]pyrrole-2,5-dione
  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

• Structure–Activity Relationship and Pharmacokinetic Studies of Sotrastaurin (AEB071), a Promising Novel Medicine for Prevention of Graft Rejection and Treatment of Psoriasis
  作者：Jürgen Wagner、Peter von Matt、Bernard Faller、Nigel G. Cooke、Rainer Albert、Richard Sedrani、Hansjörg Wiegand、Christian Jean、Christian Beerli、Gisbert Weckbecker、Jean-Pierre Evenou、Gerhard Zenke、Sylvain Cottens

  DOI：10.1021/jm200469u

  日期：2011.9.8

  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.