tert-butyl 5-(4-(hydroxycarbamoyl)benzyl)-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate | 1354547-28-6

• 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: tert-butyl 5-(4-(hydroxycarbamoyl)benzyl)-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate
• 英文别名: tert-butyl 5-[[4-(hydroxycarbamoyl)phenyl]methyl]-3,4-dihydro-1H-pyrido[4,3-b]indole-2-carboxylate
• CAS: 1354547-28-6
• 化学式: C₂₄H₂₇N₃O₄
• 分子量: 421.496
• InChiKey: JGYQOSVQMZKFGD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  83.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2,3,4,5-四氢-1H-吡啶并[4,3-b]吲哚 在 盐酸羟胺 、 potassium tert-butylate 、 sodium methylate 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 26.25h， 生成 tert-butyl 5-(4-(hydroxycarbamoyl)benzyl)-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate
  参考文献：
  名称：

  Second-Generation Histone Deacetylase 6 Inhibitors Enhance the Immunosuppressive Effects of Foxp3+ T-Regulatory Cells

  摘要：

  Second-generation Tubastatin A analogues were synthesized and evaluated for their ability to inhibit selectively histone deacetylase 6 (HDAC6). Substitutions to the carboline cap group were well-tolerated with substitution at the 2-position of both beta- and gamma-carbolines being optimal for HDAC6 activity and selectivity. Some compounds in this series were determined to have subnanomolar activity at HDAC6 with more than 7000 fold selectivity for HDAC6 versus HDAC1. Selected compounds were then evaluated for their ability to augment the immunosuppressive effect of Foxp3+ regulatory T cells. All compounds tested were found to enhance the ability of regulatory T cells to inhibit the mitotic division of effector T cells both in vitro and in vivo, suggesting that further investigation into the use of these compounds for the treatment of autoimmune disorders is warranted.

  DOI：

  10.1021/jm200773h

文献信息

• HDAC INHIBITORS AND THERAPEUTIC METHODS USING THE SAME
  申请人：The Board of Trustees of the University of Illinois

  公开号：EP2456757B1

  公开（公告）日：2019-05-01
• Second-Generation Histone Deacetylase 6 Inhibitors Enhance the Immunosuppressive Effects of Foxp3+ T-Regulatory Cells
  作者：Jay H. Kalin、Kyle V. Butler、Tatiana Akimova、Wayne W. Hancock、Alan P. Kozikowski

  DOI：10.1021/jm200773h

  日期：2012.1.26

  Second-generation Tubastatin A analogues were synthesized and evaluated for their ability to inhibit selectively histone deacetylase 6 (HDAC6). Substitutions to the carboline cap group were well-tolerated with substitution at the 2-position of both beta- and gamma-carbolines being optimal for HDAC6 activity and selectivity. Some compounds in this series were determined to have subnanomolar activity at HDAC6 with more than 7000 fold selectivity for HDAC6 versus HDAC1. Selected compounds were then evaluated for their ability to augment the immunosuppressive effect of Foxp3+ regulatory T cells. All compounds tested were found to enhance the ability of regulatory T cells to inhibit the mitotic division of effector T cells both in vitro and in vivo, suggesting that further investigation into the use of these compounds for the treatment of autoimmune disorders is warranted.