2-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)ethyl 4-(5-((2-chloroethyl)(2-hydroxyethyl)amino)-1-methyl-1H-benzo[d]imidazol-2-yl)butanoate | 1247136-74-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 2-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)ethyl 4-(5-((2-chloroethyl)(2-hydroxyethyl)amino)-1-methyl-1H-benzo[d]imidazol-2-yl)butanoate
• CAS: 1247136-74-8
• 化学式: C₂₂H₂₇ClN₄O₅
• 分子量: 462.933
• InChiKey: SWIACCJLBJDKEV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  32.0
• 可旋转键数：
  12.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  104.97
• 氢给体数：
  1.0
• 氢受体数：
  8.0

反应信息

• 作为产物：
  描述：

  2-{4-[6-bis(2-chloroethyl)amino-3-methylbenzo[d]imidazol-2-yl]butanoyl}oxyethylmaleimide 在 水 作用下， 反应 8.0h， 以38%的产率得到2-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)ethyl 4-(5-((2-chloroethyl)(2-hydroxyethyl)amino)-1-methyl-1H-benzo[d]imidazol-2-yl)butanoate
  参考文献：
  名称：

  Optimization of the N-Lost Drugs Melphalan and Bendamustine: Synthesis and Cytotoxicity of a New Set of Dendrimer−Drug Conjugates as Tumor Therapeutic Agents

  摘要：

  Bendamustine and melphalan are very promising alkylating drugs with applicability in the treatment of various tumoral diseases, e.g., chronic lymphocytic leukemia (CLL) or breast cancer. However, numerous adverse effects limited their use. Therefore, 1,3,5-tris(3-aminopropyl)benzene (G0) and its G1 analogue 3,5-bis(3-aminopropyl)-N-(3-{3,5-bis[3-{3,5-bis(3-aminopropyl)benzoylamino}propyl]phenyl}propyl)benzamide were selected to design cytostatic drug-dendrimer conjugates to achieve tumor cell accumulation by endocytosis as already demonstrated for platinum complexes. The dendrimers act as carriers and an N-(2-hydroxyethyl)maleimide spacer between drug and carrier should guarantee a selective release of the cytostatics in the tumor cells. The resulting cytotoxicity was determined in vitro using the human MCF-7 and MDA-MB-231 breast cancer cell lines. It was demonstrated that melphalan caused cytotoxic effects depending on its free amino group (Boc protection strongly decreased the activity) but independent of a derivation of the carboxylic group (dendrimers and spacer binding). Esterification of bendamustine with the N-(2-hydroxyethyl)maleimide spacer strongly increased the hydrolytic stability of the N-lost moiety, so antiproliferative effects were yet observed in vitro.

  DOI：

  10.1021/bc900453f