2-(1-{3-[(tert-butyl)dimethylsilanyloxy]propyl}-1H-indol-3-yl)acetamide | 257874-86-5

• 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: 2-(1-{3-[(tert-butyl)dimethylsilanyloxy]propyl}-1H-indol-3-yl)acetamide
• 英文别名: 2-{1-[3-(tert-butyldimethylsilyloxy)propyl]-1H-indol-3-yl}acetamide；1-[3-(tert-butyldimethylsilyloxy)propyl]-1H-indol-3-ylacetamide；2-{1-[3-(Tert-butyl-dimethyl-silanyloxy)-propyl]-1H-indol-3-YL}-acetamide；2-[1-[3-[tert-butyl(dimethyl)silyl]oxypropyl]indol-3-yl]acetamide
• CAS: 257874-86-5
• 化学式: C₁₉H₃₀N₂O₂Si
• 分子量: 346.545
• InChiKey: NCWWPFHNNNVQIC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.08
• 重原子数：
  24
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  57.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(1-{3-[(tert-butyl)dimethylsilanyloxy]propyl}-1H-indol-3-yl)acetamide 在 potassium tert-butylate 、 四丁基氟化铵 、 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 生成 3-[1-(3-hydroxypropyl)-1H-indol-3-yl]-4-(phenylamino)-1H-pyrrole-2,5-dione
  参考文献：
  名称：

  Synthesis of anilino-monoindolylmaleimides as potent and selective PKCβ inhibitors

  摘要：

  We report herein synthesis of PKCbeta-selective inhibitors possessing the novel pharmacophore of anilino-monoindolylmalcimide. Several compounds of this series exhibited IC50's as low as 50nM against human PKCbeta2. One of the most potent compounds, 61, inhibited PKCbeta1 and PKCbeta2 with IC50 of 21 and 5nM, respectively, and exhibited selectivity of more than 60-fold in favor of PKCbeta2 relative to other PKC isozymes (PKCalpha, PKCgamma, and PKCepsilon). (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.07.061
• 作为产物：
  描述：

  3-吲哚乙酰胺 、 (3-溴丙氧基)叔丁基二甲基硅烷 以 N,N-二甲基甲酰胺 为溶剂， 以85%的产率得到2-(1-{3-[(tert-butyl)dimethylsilanyloxy]propyl}-1H-indol-3-yl)acetamide
  参考文献：
  名称：

  DISUBSTITUTED MALEIMIDE COMPOUNDS AND MEDICINAL UTILIZATION THEREOF

  摘要：

  本发明涉及一种二取代马来酰亚胺化合物，其化学式为[I]，其中R1为氢或烷基，R2为芳基、环烷基或杂环基，R3、R5、R6、R7和R8为氢、卤素、羟基、氨基、烷基或烷氧基，R4为W或R4和R3，或R4和R5共同形成具有环上取代基W的环，其中W为-(CH2)l-(Y)m-(CH2)n-Z，或其药学上可接受的盐，含有该化合物的药物组合物，以及蛋白激酶C（PKC）β抑制剂。本发明的化合物选择性地抑制PKCβ，并可作为安全有效的药物或预防剂用于对抗由PKC引起的疾病，包括糖尿病并发症。

  公开号：

  EP1120414A1

文献信息

• Synthesis and biological evaluation of novel 4-azaindolyl-indolyl-maleimides as glycogen synthase kinase-3β (GSK-3β) inhibitors
  作者：Qing Ye、Guiqing Xu、Dan Lv、Zhe Cheng、Jia Li、Yongzhou Hu

  DOI：10.1016/j.bmc.2009.05.031

  日期：2009.7

  A series of novel 4-azaindolyl-indolyl-maleimides were synthesized and evaluated for their GSK-3 beta inhibitory activity. Most compounds exhibited high potency to GSK-3 beta. Among them, compound 7c was the most promising GSK-3 beta inhibitor. Preliminary structure-activity relationships were discussed based on the experimental data obtained and showed that different substituents on the indole ring and side chains at 1-position of indole had varying degrees of influence on the GSK-3 beta inhibitory potency. In a cell-based functional assay, compounds 7c and 15a significantly reduced A beta-induced Tau hyperphosphorylation by inhibiting GSK-3 beta. (C) 2009 Elsevier Ltd. All rights reserved.