KE3 | 197956-35-7

• 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: KE3
• 英文别名: (4-{[3-(1,3-dioxoisoindolin-2-yl)-2,6-dioxopiperidin-1-yl]methoxy}-4-oxobutanoic acid)；4-[[3-(1,3-Dioxoisoindol-2-yl)-2,6-dioxopiperidin-1-yl]methoxy]-4-oxobutanoic acid；4-[[3-(1,3-dioxoisoindol-2-yl)-2,6-dioxopiperidin-1-yl]methoxy]-4-oxobutanoic acid
• CAS: 197956-35-7
• 化学式: C₁₈H₁₆N₂O₈
• 分子量: 388.334
• InChiKey: YOWRDLNSDFQEAK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  138
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  KE3 、 c,c,t-[Pt(NH₃)2Cl₂(OH)2] 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三甲胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.42h， 以55.4%的产率得到(cis,cis-diamminedichloro-bis{4-{[3-(1,3-dioxoisoindolin-2-yl)-2,6-dioxopiperidin-1-yl]methoxy}-4-oxobutanoic}platinum(IV))
  参考文献：
  名称：

  Thalidomide-based Pt(IV) prodrugs designed to exert synergistic effect of immunomodulation and chemotherapy

  摘要：

  DOI：

  10.1016/j.jinorgbio.2022.111842
• 作为产物：
  描述：

  沙利度胺 在 4-吡咯烷基吡啶 、 三乙胺 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 24.0h， 生成 KE3
  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

文献信息

• Synthesis and immunological activity of water-soluble Thalidomide prodrugs
  作者：S Hess

  DOI：10.1016/s0968-0896(00)00342-4

  日期：2001.5

  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.
• Thalidomide-based Pt(IV) prodrugs designed to exert synergistic effect of immunomodulation and chemotherapy
  作者：Zhe Li、Xiao-Jing Ding、Xin Qiao、Xiao-Meng Liu、Xin Qiao、Cheng-Zhi Xie、Rui-Ping Liu、Jing-Yuan Xu

  DOI：10.1016/j.jinorgbio.2022.111842

  日期：2022.7