2-(1-iodomethyl-2,6-dioxo-piperidine-3-yl)-1,3-dihydro-2H-isoindole-1,3-dione | 359869-13-9

• 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: 2-(1-iodomethyl-2,6-dioxo-piperidine-3-yl)-1,3-dihydro-2H-isoindole-1,3-dione
• 英文别名: (R,S)-2-(1-(iodomethyl)-2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione；2-[1-(Iodomethyl)-2,6-dioxopiperidin-3-yl]isoindole-1,3-dione
• CAS: 359869-13-9
• 化学式: C₁₄H₁₁IN₂O₄
• 分子量: 398.157
• InChiKey: GJPPGHLZNCSYLB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  74.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(1-iodomethyl-2,6-dioxo-piperidine-3-yl)-1,3-dihydro-2H-isoindole-1,3-dione 在 sodium azide 作用下， 以 丙酮 为溶剂， 反应 24.0h， 以66%的产率得到(R,S)-2-(1-(azidomethyl)-2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione
  参考文献：
  名称：

  Efforts toward elucidating Thalidomide’s molecular target: an expedient synthesis of the first Thalidomide biotin analogue

  摘要：

  在这里，我们描述了第一种沙利度胺-生物素类似物的合成，以启动对沙利度胺未知分子作用机制的研究。我们采用Huisgen 1,3-双极环加成或“点击”合成方法，描述了生物素连接体的结合。

  DOI：

  10.1039/c0ob00060d
• 作为产物：
  描述：

  沙利度胺 在 氯化亚砜 、 potassium iodide 作用下， 以 水 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 7.0h， 生成 2-(1-iodomethyl-2,6-dioxo-piperidine-3-yl)-1,3-dihydro-2H-isoindole-1,3-dione
  参考文献：
  名称：

  Synthesis and immunological activity of water-soluble Thalidomide prodrugs

  摘要：

  A series of new water-soluble thalidomide prodrugs was prepared. All compounds were derivatized on the nitrogen of the glutarimide ring. Esters of natural amino acids and succinic acid derivatives have been introduced by reaction with the hydroxymethyl thalidomide 2. Nicotinic acid derivatives were prepared from halomethyl derivatives. Additionally, a methoxy methyl derivative and a carboxymethyl derivative were prepared directly from thalidomide. Most compounds showed a very large increase in water solubility compared to thalidomide itself (0.012 mg/mL). The amorphous hydrochlorides of the N-methylalanine ester 8, valine ester 9, and glycylglycine ester 10, respectively, were the most soluble compounds showing solubility greater than 300 mg/mL, which equals an increase greater than 15,000-fold. The lipophilicity of the prodrugs has been determined by their HPLC capacity factors k '. The stability of selected compounds was determined. The hydrolysis rates follow pseudo-first order kinetics. In order to assess the immunological activity, the prodrugs were tested using tumor necrosis factor-alpha and interleukin-2 inhibition assays. Selected compounds were additionally investigated on their abililty to inhibit the local Shwartzman reaction, an assay to determine the Vascular permeability. The prodrugs retained high effectiveness in the inhibition of TNF-alpha release. Our results indicated that the more stable prodrugs exhibited higher activity in the immunological assays. Some compounds showed higher activity than thalidomide itself, suggesting a high affine binding to the pharmacophore. In conclusion, the prodrugs exhibited high water solubility and high activity and might therefore be used in therapeutic applications. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00342-4