3-[4-(3-benzyloxycarbonylaminopropoxy)-3,5-dibromophenyl]-2-benzyloxyiminopropanoic acid | 882687-09-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: 3-[4-(3-benzyloxycarbonylaminopropoxy)-3,5-dibromophenyl]-2-benzyloxyiminopropanoic acid
• 英文别名: 3-[3,5-dibromo-4-[3-(phenylmethoxycarbonylamino)propoxy]phenyl]-2-phenylmethoxyiminopropanoic acid
• CAS: 882687-09-4
• 化学式: C₂₇H₂₆Br₂N₂O₆
• 分子量: 634.321
• InChiKey: QVOLLKBOLHOYAR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.11
• 重原子数：
  37.0
• 可旋转键数：
  13.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  106.45
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  3-[4-(3-benzyloxycarbonylaminopropoxy)-3,5-dibromophenyl]-2-benzyloxyiminopropanoic acid 、 2-氨基组胺 在 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 以66%的产率得到benzyl N-[3-[4-[3-[2-(2-amino-1H-imidazol-5-yl)ethylamino]-3-oxo-2-phenylmethoxyiminopropyl]-2,6-dibromophenoxy]propyl]carbamate
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Purealin and Analogues as Cytoplasmic Dynein Heavy Chain Inhibitors

  摘要：

  Cytoplasmic dynein plays important roles in membrane transport, mitosis, and other cellular processes. A few small-molecule inhibitors of cytoplasmic dynein have been identified. We report here the first synthesis of purealin, a natural product isolated from the sea sponge Psammaplysilla purea, which is known to inhibit axonemal dynein. Also described are the first syntheses, by modular amide coupling reactions, of the natural product purealidin A (a component of purealin) and a small library of analogues. The library was examined for inhibition of cytoplasmic dynein heavy chain and cell growth. The compounds showed effective antiproliferative activity against a mouse leukemia cell line but selective activities against human carcinoma cell lines. Purealin and some of the analogues inhibited the microtubule-stimulated ATPase activity of recombinant cytoplasmic dynein heavy chain motor domain. The inhibitory effect of purealin was concentration dependent and uncompetitive, supporting the hypothesis that it does not compete with the binding of ATP.

  DOI：

  10.1021/jm051030l
• 作为产物：
  描述：

  benzyl [3-(2,6-dibromo-4-formylphenoxy)propyl]carbamate 在 barium dihydroxide 、 sodium acetate 、 乙酸酐 作用下， 以 1,4-二氧六环 为溶剂， 反应 11.0h， 生成 3-[4-(3-benzyloxycarbonylaminopropoxy)-3,5-dibromophenyl]-2-benzyloxyiminopropanoic acid
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Purealin and Analogues as Cytoplasmic Dynein Heavy Chain Inhibitors

  摘要：

  Cytoplasmic dynein plays important roles in membrane transport, mitosis, and other cellular processes. A few small-molecule inhibitors of cytoplasmic dynein have been identified. We report here the first synthesis of purealin, a natural product isolated from the sea sponge Psammaplysilla purea, which is known to inhibit axonemal dynein. Also described are the first syntheses, by modular amide coupling reactions, of the natural product purealidin A (a component of purealin) and a small library of analogues. The library was examined for inhibition of cytoplasmic dynein heavy chain and cell growth. The compounds showed effective antiproliferative activity against a mouse leukemia cell line but selective activities against human carcinoma cell lines. Purealin and some of the analogues inhibited the microtubule-stimulated ATPase activity of recombinant cytoplasmic dynein heavy chain motor domain. The inhibitory effect of purealin was concentration dependent and uncompetitive, supporting the hypothesis that it does not compete with the binding of ATP.

  DOI：

  10.1021/jm051030l