5-(3-acetyl-1-methyl-1H-indol-5-yl)thiophene-2-carbaldehyde

• 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: 5-(3-acetyl-1-methyl-1H-indol-5-yl)thiophene-2-carbaldehyde
• 英文别名: 5-(3-Acetyl-1-methylindol-5-yl)thiophene-2-carbaldehyde；5-(3-acetyl-1-methylindol-5-yl)thiophene-2-carbaldehyde
• 化学式: C₁₆H₁₃NO₂S
• 分子量: 283.351
• InChiKey: UXXDMOYPPZVFOW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  67.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-硫代乙内酰脲 、 5-(3-acetyl-1-methyl-1H-indol-5-yl)thiophene-2-carbaldehyde 在 溶剂黄146 、 β-丙氨酸 作用下， 反应 15.0h， 以73%的产率得到5-((5-(3-acetyl-1-methyl-1H-indol-5-yl)thiophen-2-yl)methylene)-2-thioxoimidazolidin-4-one
  参考文献：
  名称：

  Exploration of a Series of 5-Arylidene-2-thioxoimidazolidin-4-ones as Inhibitors of the Cytolytic Protein Perforin

  摘要：

  A series of novel 5-arylidene-2-thioxoimidazolidin-4-ones were investigated as inhibitors of the lymphocyte-expressed pore-forming protein perform. Structure activity relationships were explored through variation of an isoindolinone or 3,4-dihydroisoquinolinone subunit on a fixed 2-thioxoimidazolidin-4-one/thiophene core. The ability of the resulting compounds to inhibit the lytic activity of both isolated perform protein and perforin delivered in situ by natural killer cells was determined. A number of compounds showed excellent activity at concentrations that were nontoxic to the killer cells, and several were a significant improvement on previous classes of inhibitors, being substantially more potent and soluble. Representative examples showed rapid and reversible binding to immobilized mouse perforin at low concentrations (<= 2.5 mu M) by surface plasmon resonance and prevented formation of perforin pores in target cells despite effective target cell engagement, as determined by calcium influx studies. Mouse PK studies of two analogues showed T-1/2 values of 1.1-1.2 h (dose of 5 mg/kg iv) and MTDs of 60-80 mg/kg (ip).

  DOI：

  10.1021/jm401604x
• 作为产物：
  描述：

  1-(5-bromo-1-(phenylsulfonyl)-1H-indol-3-yl)ethanone 在 盐酸 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 四丁基溴化铵 、 potassium hydrogencarbonate 、 caesium carbonate 作用下， 以 水 、 N,N-二甲基甲酰胺 、 丙酮 、 甲苯 为溶剂， 反应 3.0h， 生成 5-(3-acetyl-1-methyl-1H-indol-5-yl)thiophene-2-carbaldehyde
  参考文献：
  名称：

  Exploration of a Series of 5-Arylidene-2-thioxoimidazolidin-4-ones as Inhibitors of the Cytolytic Protein Perforin

  摘要：

  A series of novel 5-arylidene-2-thioxoimidazolidin-4-ones were investigated as inhibitors of the lymphocyte-expressed pore-forming protein perform. Structure activity relationships were explored through variation of an isoindolinone or 3,4-dihydroisoquinolinone subunit on a fixed 2-thioxoimidazolidin-4-one/thiophene core. The ability of the resulting compounds to inhibit the lytic activity of both isolated perform protein and perforin delivered in situ by natural killer cells was determined. A number of compounds showed excellent activity at concentrations that were nontoxic to the killer cells, and several were a significant improvement on previous classes of inhibitors, being substantially more potent and soluble. Representative examples showed rapid and reversible binding to immobilized mouse perforin at low concentrations (<= 2.5 mu M) by surface plasmon resonance and prevented formation of perforin pores in target cells despite effective target cell engagement, as determined by calcium influx studies. Mouse PK studies of two analogues showed T-1/2 values of 1.1-1.2 h (dose of 5 mg/kg iv) and MTDs of 60-80 mg/kg (ip).

  DOI：

  10.1021/jm401604x

文献信息

• Exploration of a Series of 5-Arylidene-2-thioxoimidazolidin-4-ones as Inhibitors of the Cytolytic Protein Perforin
  作者：Julie A. Spicer、Gersande Lena、Dani M. Lyons、Kristiina M. Huttunen、Christian K. Miller、Patrick D. O’Connor、Matthew Bull、Nuala Helsby、Stephen M. F. Jamieson、William A. Denny、Annette Ciccone、Kylie A. Browne、Jamie A. Lopez、Jesse Rudd-Schmidt、Ilia Voskoboinik、Joseph A. Trapani

  DOI：10.1021/jm401604x

  日期：2013.12.12

  A series of novel 5-arylidene-2-thioxoimidazolidin-4-ones were investigated as inhibitors of the lymphocyte-expressed pore-forming protein perform. Structure activity relationships were explored through variation of an isoindolinone or 3,4-dihydroisoquinolinone subunit on a fixed 2-thioxoimidazolidin-4-one/thiophene core. The ability of the resulting compounds to inhibit the lytic activity of both isolated perform protein and perforin delivered in situ by natural killer cells was determined. A number of compounds showed excellent activity at concentrations that were nontoxic to the killer cells, and several were a significant improvement on previous classes of inhibitors, being substantially more potent and soluble. Representative examples showed rapid and reversible binding to immobilized mouse perforin at low concentrations (<= 2.5 mu M) by surface plasmon resonance and prevented formation of perforin pores in target cells despite effective target cell engagement, as determined by calcium influx studies. Mouse PK studies of two analogues showed T-1/2 values of 1.1-1.2 h (dose of 5 mg/kg iv) and MTDs of 60-80 mg/kg (ip).