ethyl 1-oxo-5-(5-((5-oxo-2-thioxoimidazolidin-4-ylidene)methyl)thiophen-2-yl)isoindoline-2-carboxylate | 1313397-70-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: ethyl 1-oxo-5-(5-((5-oxo-2-thioxoimidazolidin-4-ylidene)methyl)thiophen-2-yl)isoindoline-2-carboxylate
• 英文别名: (E,Z)-ethyl 1-oxo-5-(5-((5-oxo-2-thioxoimidazolidin-4-ylidene)methyl)thiophen-2-yl)isoindoline-2-carboxylate；ethyl 3-oxo-6-[5-[(5-oxo-2-sulfanylideneimidazolidin-4-ylidene)methyl]thiophen-2-yl]-1H-isoindole-2-carboxylate
• CAS: 1313397-70-4
• 化学式: C₁₉H₁₅N₃O₄S₂
• 分子量: 413.478
• InChiKey: PVHSBYVFVRQXQK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  148
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  5-(5-(1,3-dioxolan-2-yl)thiophen-2-yl)isoindolin-1-one 在 盐酸 、 sodium hydride 、 溶剂黄146 、 β-丙氨酸 作用下， 以 水 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 16.0h， 生成 ethyl 1-oxo-5-(5-((5-oxo-2-thioxoimidazolidin-4-ylidene)methyl)thiophen-2-yl)isoindoline-2-carboxylate
  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