Z-D-Val-Leu-Lys(Z)-N(Me)-(CH2)2-N(Me)-Boc | 294173-05-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: Z-D-Val-Leu-Lys(Z)-N(Me)-(CH2)2-N(Me)-Boc
• 英文别名: tert-butyl N-methyl-N-[2-[methyl-[(2S)-2-[[(2S)-4-methyl-2-[[(2R)-3-methyl-2-(phenylmethoxycarbonylamino)butanoyl]amino]pentanoyl]amino]-6-(phenylmethoxycarbonylamino)hexanoyl]amino]ethyl]carbamate
• CAS: 294173-05-0
• 化学式: C₄₂H₆₄N₆O₉
• 分子量: 797.005
• InChiKey: WWPWBMAFCSWQKJ-PUPDPRJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  57
• 可旋转键数：
  25
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  185
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  Z-D-Val-Leu-Lys(Z)-N(Me)-(CH2)2-N(Me)-Boc 在 盐酸 作用下， 以 乙酸乙酯 为溶剂， 反应 4.0h， 以100%的产率得到Z-D-Val-Leu-Lys(Z)-N(Me)-(CH2)2-N(Me) hydrochloride
  参考文献：
  名称：

  Synthesis and Biological Evaluation of 2‘-Carbamate-Linked and 2‘-Carbonate-Linked Prodrugs of Paclitaxel:  Selective Activation by the Tumor-Associated Protease Plasmin

  摘要：

  The nontoxic paclitaxel-2'-carbamate prodrugs 2-5 and paclitaxel-2'-carbonate prodrug 6 were synthesized and tested for activation by the tumor-associated enzyme plasmin. A generally applicable method for the synthesis of paditaxel-2'-carbamates was developed. In buffer solution, prodrug 2, which contained an unsubstituted ethylenediamine spacer, was not stable, whereas prodrugs 3-6 were highly stable. Prodrugs 3-6 showed on average a decrease in cytotoxicity of more than 8000-fold in comparison with the parent drug in seven human tumor cell lines. Prodrugs 5 and 6 are the most nontoxic prodrugs of paclitaxel that yield the free parent drug upon selective activation currently reported. Enzyme hydrolysis and spacer elimination rates were determined by incubation of prodrugs 5 and 6 in the presence of human plasmin. From these results, prodrug 6 was selected as the promising prodrug for further in vivo studies.

  DOI：

  10.1021/jm0009078
• 作为产物：
  描述：

  Boc-D-Val-Leu-Lys(Boc)-OBu 在 盐酸 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙酸乙酯 、 乙腈 为溶剂， 反应 6.0h， 生成 Z-D-Val-Leu-Lys(Z)-N(Me)-(CH2)2-N(Me)-Boc
  参考文献：
  名称：

  Synthesis and Biological Evaluation of 2‘-Carbamate-Linked and 2‘-Carbonate-Linked Prodrugs of Paclitaxel:  Selective Activation by the Tumor-Associated Protease Plasmin

  摘要：

  The nontoxic paclitaxel-2'-carbamate prodrugs 2-5 and paclitaxel-2'-carbonate prodrug 6 were synthesized and tested for activation by the tumor-associated enzyme plasmin. A generally applicable method for the synthesis of paditaxel-2'-carbamates was developed. In buffer solution, prodrug 2, which contained an unsubstituted ethylenediamine spacer, was not stable, whereas prodrugs 3-6 were highly stable. Prodrugs 3-6 showed on average a decrease in cytotoxicity of more than 8000-fold in comparison with the parent drug in seven human tumor cell lines. Prodrugs 5 and 6 are the most nontoxic prodrugs of paclitaxel that yield the free parent drug upon selective activation currently reported. Enzyme hydrolysis and spacer elimination rates were determined by incubation of prodrugs 5 and 6 in the presence of human plasmin. From these results, prodrug 6 was selected as the promising prodrug for further in vivo studies.

  DOI：

  10.1021/jm0009078

文献信息

• Synthesis and Biological Evaluation of 2‘-Carbamate-Linked and 2‘-Carbonate-Linked Prodrugs of Paclitaxel:  Selective Activation by the Tumor-Associated Protease Plasmin
  作者：Franciscus M. H. de Groot、Leon W. A. van Berkom、Hans W. Scheeren

  DOI：10.1021/jm0009078

  日期：2000.8.1

  The nontoxic paclitaxel-2'-carbamate prodrugs 2-5 and paclitaxel-2'-carbonate prodrug 6 were synthesized and tested for activation by the tumor-associated enzyme plasmin. A generally applicable method for the synthesis of paditaxel-2'-carbamates was developed. In buffer solution, prodrug 2, which contained an unsubstituted ethylenediamine spacer, was not stable, whereas prodrugs 3-6 were highly stable. Prodrugs 3-6 showed on average a decrease in cytotoxicity of more than 8000-fold in comparison with the parent drug in seven human tumor cell lines. Prodrugs 5 and 6 are the most nontoxic prodrugs of paclitaxel that yield the free parent drug upon selective activation currently reported. Enzyme hydrolysis and spacer elimination rates were determined by incubation of prodrugs 5 and 6 in the presence of human plasmin. From these results, prodrug 6 was selected as the promising prodrug for further in vivo studies.