3-(7-Hydroxymethyl-7,8,9,10-tetrahydro-6H-azepino[1,2-a]indol-11-yl)-4-(1-methyl-1H-indol-3-yl)-pyrrole-2,5-dione | 145317-10-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - Pyrroloazepines
• 英文名称: 3-(7-Hydroxymethyl-7,8,9,10-tetrahydro-6H-azepino[1,2-a]indol-11-yl)-4-(1-methyl-1H-indol-3-yl)-pyrrole-2,5-dione
• 英文别名: 3-[7-(hydroxymethyl)-7,8,9,10-tetrahydro-6H-azepino[1,2-a]indol-11-yl]-4-(1-methylindol-3-yl)pyrrole-2,5-dione
• CAS: 145317-10-8
• 化学式: C₂₇H₂₅N₃O₃
• 分子量: 439.514
• InChiKey: GOBPIRQTJNKXTR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  33
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  76.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(7-Hydroxymethyl-7,8,9,10-tetrahydro-6H-azepino[1,2-a]indol-11-yl)-4-(1-methyl-1H-indol-3-yl)-pyrrole-2,5-dione 在 2,4,6-三甲基吡啶 、 ammonium hydroxide 作用下， 以 二氯甲烷 为溶剂， 反应 19.0h， 生成 3-(7-Aminomethyl-7,8,9,10-tetrahydro-6H-azepino[1,2-a]indol-11-yl)-4-(1-methyl-1H-indol-3-yl)-pyrrole-2,5-dione
  参考文献：
  名称：

  Inhibitors of protein kinase C. 3. Potent and highly selective bisindolylmaleimides by conformational restriction

  摘要：

  The protein kinase inhibitor staurosporine has been used to design a series of selective bisindolylmaleimide inhibitors of protein kinase C (PKC). Guided by molecular graphics, conformational restriction of the cationic side chain has led to ATP competitive inhibitors of improved potency and selectivity. Two compounds have been further evaluated and were shown to inhibit PKC of human origin and prevent T-cell activation in a human allogeneic mixed lymphocyte reaction. One of these compounds was orally absorbed in mice and antagonized a phorbol ester induced paw edema in a dose-dependent manner. This compound also selectively inhibited the secondary T-cell mediated response in a developing adjuvant arthritis model in rats and provides evidence for the potential use of PKC inhibitors as therapeutic immunomodulators.

  DOI：

  10.1021/jm00053a003
• 作为产物：
  描述：

  7-(acetoxymethyl)-7,8,9,10-tetrahydro-6H-azepino<1,2-a>indole 在 ammonium hydroxide 、 三乙胺 作用下， 以 乙醚 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 74.5h， 生成 3-(7-Hydroxymethyl-7,8,9,10-tetrahydro-6H-azepino[1,2-a]indol-11-yl)-4-(1-methyl-1H-indol-3-yl)-pyrrole-2,5-dione
  参考文献：
  名称：

  Inhibitors of protein kinase C. 3. Potent and highly selective bisindolylmaleimides by conformational restriction

  摘要：

  The protein kinase inhibitor staurosporine has been used to design a series of selective bisindolylmaleimide inhibitors of protein kinase C (PKC). Guided by molecular graphics, conformational restriction of the cationic side chain has led to ATP competitive inhibitors of improved potency and selectivity. Two compounds have been further evaluated and were shown to inhibit PKC of human origin and prevent T-cell activation in a human allogeneic mixed lymphocyte reaction. One of these compounds was orally absorbed in mice and antagonized a phorbol ester induced paw edema in a dose-dependent manner. This compound also selectively inhibited the secondary T-cell mediated response in a developing adjuvant arthritis model in rats and provides evidence for the potential use of PKC inhibitors as therapeutic immunomodulators.

  DOI：

  10.1021/jm00053a003