N,N-(N,N-phthaloyl-glutamoyl)-glycine | 100881-15-0

• 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: N,N-(N,N-phthaloyl-glutamoyl)-glycine
• 英文别名: N,N-(N,N-Phthaloyl-glutamoyl)-glycin；2-[3-(1,3-Dioxoisoindol-2-yl)-2,6-dioxopiperidin-1-yl]acetic acid
• CAS: 100881-15-0
• 化学式: C₁₅H₁₂N₂O₆
• 分子量: 316.27
• InChiKey: YXYRTJULTFUCGG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  112
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N,N-(N,N-phthaloyl-glutamoyl)-glycine 、 2-[2-[2-[(2-Oxo-2-phenylmethoxyethyl)-phenylmethoxycarbonylamino]ethoxy]ethoxy]ethylazanium;2,2,2-trifluoroacetate 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以77%的产率得到(benzyloxycarbonyl-{2-[2-(2-{2-[3-(1,3-dioxo-1,3-dihydroisoindol-2-yl)-2,6-dioxo-piperidin-1-yl]-acetylamino}-ethoxy)-ethoxy]-ethyl}-amino)-acetic acid benzyl ester
  参考文献：
  名称：

  新型抗炎药C（60）富勒吡咯烷-沙利度胺二联体的开发和生物学评估。

  摘要：

  由于发现了这些化合物的广泛的生物活性，C（60）富勒烯衍生物领域的研究显着增加。我们设计并准备了一种新的带有沙利度胺的C（60）富勒烯杂化物，作为潜在的双重作用抗炎药，能够同时抑制LPS诱导的NO和TNF-α的产生。C（60）Fulleropyrrolidine-thalidomide dyad，CLT，是抑制LPS刺激的巨噬细胞RAW 264.7释放NO和TNF-α的有效药物。相对于对照，十微摩尔的CLT有效抑制LPS诱导的NO和TNF-α产生分别为47.3 +/- 4.2％和70.2 +/- 4％。此外，初步的生化研究表明，CLT是抑制LPS诱导的细胞内ROS产生和iNOS表达的有效剂，并且CLT也抑制ERK的磷酸化，ERK是参与LPS激活的TNF-α合成激活的重要蛋白激酶。巨噬细胞。我们相信本文的研究将为新一代强效抗炎药的未来发展带来希望。

  DOI：

  10.1016/j.bmc.2008.08.004
• 作为产物：
  描述：

  沙利度胺 在 sodium hydride 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 25.0h， 生成 N,N-(N,N-phthaloyl-glutamoyl)-glycine
  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

• King et al., Journal of the Chemical Society, 1957, p. 873,879
  作者：King et al.

  DOI：——

  日期：——
• 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.
• Development and biological evaluation of C60 fulleropyrrolidine-thalidomide dyad as a new anti-inflammation agent
  作者：Sheng-Tung Huang、Chia-Shin Ho、Chun-Mao Lin、Hsu-Wei Fang、Yi-Xiang Peng

  DOI：10.1016/j.bmc.2008.08.004

  日期：2008.9

  studies in the field of C(60) fullerene derivatives have significantly increased due to the broad range of biological activities that were found for these compounds. We designed and prepared a new C(60) fullerene hybrid bearing thalidomide as a potential double-action anti-inflammatory agent, capable of simultaneous inhibition of LPS-induced NO and TNF-alpha production. The C(60) fulleropyrrolidine-thalidomide

  由于发现了这些化合物的广泛的生物活性，C（60）富勒烯衍生物领域的研究显着增加。我们设计并准备了一种新的带有沙利度胺的C（60）富勒烯杂化物，作为潜在的双重作用抗炎药，能够同时抑制LPS诱导的NO和TNF-α的产生。C（60）Fulleropyrrolidine-thalidomide dyad，CLT，是抑制LPS刺激的巨噬细胞RAW 264.7释放NO和TNF-α的有效药物。相对于对照，十微摩尔的CLT有效抑制LPS诱导的NO和TNF-α产生分别为47.3 +/- 4.2％和70.2 +/- 4％。此外，初步的生化研究表明，CLT是抑制LPS诱导的细胞内ROS产生和iNOS表达的有效剂，并且CLT也抑制ERK的磷酸化，ERK是参与LPS激活的TNF-α合成激活的重要蛋白激酶。巨噬细胞。我们相信本文的研究将为新一代强效抗炎药的未来发展带来希望。