benzyl (2S)-2-[[(2S)-1-[[2-[(2S)-2-[[2-[4-[bis(2-chloroethyl)amino]anilino]-2-oxoethyl]carbamoyl]pyrrolidin-1-yl]-2-oxoethyl]amino]-4-methyl-1-oxopentan-2-yl]carbamoyl]pyrrolidine-1-carboxylate | 68427-15-6

• 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: benzyl (2S)-2-[[(2S)-1-[[2-[(2S)-2-[[2-[4-[bis(2-chloroethyl)amino]anilino]-2-oxoethyl]carbamoyl]pyrrolidin-1-yl]-2-oxoethyl]amino]-4-methyl-1-oxopentan-2-yl]carbamoyl]pyrrolidine-1-carboxylate
• CAS: 68427-15-6
• 化学式: C₃₈H₅₁Cl₂N₇O₇
• 分子量: 788.772
• InChiKey: SCJZRTLUUMTJHZ-CPCREDONSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  54
• 可旋转键数：
  19
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  170
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  benzyl (2S)-2-[[(2S)-1-[[2-[(2S)-2-[[2-[4-[bis(2-chloroethyl)amino]anilino]-2-oxoethyl]carbamoyl]pyrrolidin-1-yl]-2-oxoethyl]amino]-4-methyl-1-oxopentan-2-yl]carbamoyl]pyrrolidine-1-carboxylate 在 氢溴酸 作用下， 以 溶剂黄146 为溶剂， 生成 (S)-1-(2-{(S)-4-Methyl-2-[((S)-pyrrolidine-2-carbonyl)-amino]-pentanoylamino}-acetyl)-pyrrolidine-2-carboxylic acid ({4-[bis-(2-chloro-ethyl)-amino]-phenylcarbamoyl}-methyl)-amide
  参考文献：
  名称：

  Synthesis and in vitro evaluation of macromolecular antitumour derivatives based on phenylenediamine mustard

  摘要：

  Poly- [N-(2-hydroxyethyl)-L-glutamine] (PHEG) and poly(ethylene glycol) (PEG)-grafted PHEG conjugates of NN-di(2-chloroethyl)-4phenylenediamine mustard (PDM) were synthetised. A collagenase-sensitive oligopeptide spacer was selected to link the cytotoxic agent PDM onto the polymeric carrier. First, the oligopeptide-drug conjugate, L-pro-L-leu-gly-L-pro-gly-PDM, was prepared. In a second step, the low molecular weight PDM derivative and PEG-NH2 were coupled to a N,N-disuccinimidylcarbonate activated PHEG. Dynamic laser light scattering measurements indicated the formation of aggregates. The presence of human serum albumin had no significant effect on the diameter of the conjugates. The hydrolytic stability of the conjugates was investigated in buffer solutions. The conjugates showed an improved stability compared to the parent nitrogen mustard. The enzymatic degradation studies of the polymeric conjugates were performed in the presence of collagenase type IV (Clostridiopeptidase A; EC 3.4.24.3), cathepsin B (EC 3.4.22.1), cathepsin D (EC 3.4.23.5) and tritosomes. Only the bacterial collagenase type IV was able to cleave the spacer releasing free PDM and its peptidyl derivative, gly-L-pro-gly-PDM. The in vitro cytotoxicity of the conjugates was evaluated against HT1080 fibrosarcoma cells and MDA adenocarcinoma cells. All conjugates showed low toxicity towards these cell lines. (C) 2004 Published by Elsevier B.V.

  DOI：

  10.1016/j.ejps.2004.09.006
• 作为产物：
  描述：

  2-[[1-(苯基甲氧羰基)吡咯烷-2-羰基]氨基]乙酸 在 N-甲基吗啉 、 氢溴酸 、 碳酸氢钠 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 水 、 溶剂黄146 为溶剂， 反应 0.5h， 生成 benzyl (2S)-2-[[(2S)-1-[[2-[(2S)-2-[[2-[4-[bis(2-chloroethyl)amino]anilino]-2-oxoethyl]carbamoyl]pyrrolidin-1-yl]-2-oxoethyl]amino]-4-methyl-1-oxopentan-2-yl]carbamoyl]pyrrolidine-1-carboxylate
  参考文献：
  名称：

  Synthesis and in vitro evaluation of macromolecular antitumour derivatives based on phenylenediamine mustard

  摘要：

  Poly- [N-(2-hydroxyethyl)-L-glutamine] (PHEG) and poly(ethylene glycol) (PEG)-grafted PHEG conjugates of NN-di(2-chloroethyl)-4phenylenediamine mustard (PDM) were synthetised. A collagenase-sensitive oligopeptide spacer was selected to link the cytotoxic agent PDM onto the polymeric carrier. First, the oligopeptide-drug conjugate, L-pro-L-leu-gly-L-pro-gly-PDM, was prepared. In a second step, the low molecular weight PDM derivative and PEG-NH2 were coupled to a N,N-disuccinimidylcarbonate activated PHEG. Dynamic laser light scattering measurements indicated the formation of aggregates. The presence of human serum albumin had no significant effect on the diameter of the conjugates. The hydrolytic stability of the conjugates was investigated in buffer solutions. The conjugates showed an improved stability compared to the parent nitrogen mustard. The enzymatic degradation studies of the polymeric conjugates were performed in the presence of collagenase type IV (Clostridiopeptidase A; EC 3.4.24.3), cathepsin B (EC 3.4.22.1), cathepsin D (EC 3.4.23.5) and tritosomes. Only the bacterial collagenase type IV was able to cleave the spacer releasing free PDM and its peptidyl derivative, gly-L-pro-gly-PDM. The in vitro cytotoxicity of the conjugates was evaluated against HT1080 fibrosarcoma cells and MDA adenocarcinoma cells. All conjugates showed low toxicity towards these cell lines. (C) 2004 Published by Elsevier B.V.

  DOI：

  10.1016/j.ejps.2004.09.006

文献信息

• Synthesis and in vitro evaluation of macromolecular antitumour derivatives based on phenylenediamine mustard
  作者：Katleen De Winne、Leonard W. Seymour、Etienne H. Schacht

  DOI：10.1016/j.ejps.2004.09.006

  日期：2005.2

  Poly- [N-(2-hydroxyethyl)-L-glutamine] (PHEG) and poly(ethylene glycol) (PEG)-grafted PHEG conjugates of NN-di(2-chloroethyl)-4phenylenediamine mustard (PDM) were synthetised. A collagenase-sensitive oligopeptide spacer was selected to link the cytotoxic agent PDM onto the polymeric carrier. First, the oligopeptide-drug conjugate, L-pro-L-leu-gly-L-pro-gly-PDM, was prepared. In a second step, the low molecular weight PDM derivative and PEG-NH2 were coupled to a N,N-disuccinimidylcarbonate activated PHEG. Dynamic laser light scattering measurements indicated the formation of aggregates. The presence of human serum albumin had no significant effect on the diameter of the conjugates. The hydrolytic stability of the conjugates was investigated in buffer solutions. The conjugates showed an improved stability compared to the parent nitrogen mustard. The enzymatic degradation studies of the polymeric conjugates were performed in the presence of collagenase type IV (Clostridiopeptidase A; EC 3.4.24.3), cathepsin B (EC 3.4.22.1), cathepsin D (EC 3.4.23.5) and tritosomes. Only the bacterial collagenase type IV was able to cleave the spacer releasing free PDM and its peptidyl derivative, gly-L-pro-gly-PDM. The in vitro cytotoxicity of the conjugates was evaluated against HT1080 fibrosarcoma cells and MDA adenocarcinoma cells. All conjugates showed low toxicity towards these cell lines. (C) 2004 Published by Elsevier B.V.