(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 | 849427-27-6

• 英文名称: (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
• CAS: 849427-27-6
• 化学式: C₃₀H₄₅Cl₂N₇O₅
• 分子量: 654.637
• InChiKey: OCSZHYCNMXFXID-SDHOMARFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.42
• 重原子数：
  44.0
• 可旋转键数：
  16.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  151.98
• 氢给体数：
  5.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  (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 在 氢溴酸 、 碳酸氢钠 作用下， 以 乙二醇二甲醚 、 水 、 溶剂黄146 为溶剂， 生成 (S)-1-(4-aminobutanoyl)-N-((S)-1-((2-((S)-2-((2-((4-(bis(2-chloroethyl)amino)phenyl)amino)-2-oxoethyl)carbamoyl)pyrrolidin-1-yl)-2-oxoethyl)amino)-4-methyl-1-oxopentan-2-yl)pyrrolidine-2-carboxamide
  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：

  benzyl (2S)-2-[[2-[4-[bis(2-chloroethyl)amino]anilino]-2-oxoethyl]carbamoyl]pyrrolidine-1-carboxylate 在 氢溴酸 、 碳酸氢钠 作用下， 以 乙二醇二甲醚 、 水 、 溶剂黄146 为溶剂， 反应 0.33h， 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