2-(4-acetylphenoxy)-N-acetamidocolchicine | 725735-04-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-(4-acetylphenoxy)-N-acetamidocolchicine
• 英文别名: 2-(4-acetylphenoxy)-N-[(7S)-1,2,3,10-tetramethoxy-9-oxo-6,7-dihydro-5H-benzo[a]heptalen-7-yl]acetamide
• CAS: 725735-04-6
• 化学式: C₃₀H₃₁NO₈
• 分子量: 533.578
• InChiKey: KPJRVIFHJMRTLI-QHCPKHFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  39
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  109
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-(4-acetylphenoxy)-N-acetamidocolchicine 、 以 甲醇 为溶剂， 反应 24.0h， 生成
  参考文献：
  名称：

  Sialic Acid Derivatives

  摘要：

  公式（I）的唾液酸衍生物，其中符号如描述中定义的那样，适用于与一种货物连接，用于调节目标生物体的代谢过程、免疫反应、免疫或脱敏。

  公开号：

  US20150174262A1
• 作为产物：
  描述：

  秋水仙碱 在 N-甲基吗啉 、 甲醇 、 4-二甲氨基吡啶 、 sodium methylate 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 、 三氟乙酸 作用下， 以 氯仿 、 乙腈 为溶剂， 反应 5.08h， 生成 2-(4-acetylphenoxy)-N-acetamidocolchicine
  参考文献：
  名称：

  Synthesis and Characterization of a Cobalamin−Colchicine Conjugate as a Novel Tumor-Targeted Cytotoxin

  摘要：

  Colchicine was derivatized at C7 with p-alkoxyacetophenone and conjugated to cobalamin (vitamin B-12) through an acid-labile hydrazone linker. The cobalamin moiety leads to preferential uptake of the cobalamin-colchicine prodrug by cancer cells, whereupon the hydrazone linker undergoes hydrolysis in the lysosome to unmask colchicine, which acts as a potent cytotoxin by stabilizing microtubules and causing cell death. The bioconjugate is stable in cell culture media and at neutral pH but undergoes hydrolysis with a half-life of 138 min at pH 4.5. The colchicine-cobalamin bioconjugate exhibits nanomolar LC50 values against breast, brain, and melanoma cancer cell lines in culture. Attachment of colchicine to cobalamin is expected to increase the therapeutic index of the drug by limiting the side effects caused by the current nonselective administration of tubulin-targeted chemotherapeutic drugs.

  DOI：

  10.1021/jo049953w

文献信息

• Synthesis and Characterization of a Cobalamin−Colchicine Conjugate as a Novel Tumor-Targeted Cytotoxin
  作者：Joshua D. Bagnato、Alanna L. Eilers、Robert A. Horton、Charles B. Grissom

  DOI：10.1021/jo049953w

  日期：2004.12.1

  Colchicine was derivatized at C7 with p-alkoxyacetophenone and conjugated to cobalamin (vitamin B-12) through an acid-labile hydrazone linker. The cobalamin moiety leads to preferential uptake of the cobalamin-colchicine prodrug by cancer cells, whereupon the hydrazone linker undergoes hydrolysis in the lysosome to unmask colchicine, which acts as a potent cytotoxin by stabilizing microtubules and causing cell death. The bioconjugate is stable in cell culture media and at neutral pH but undergoes hydrolysis with a half-life of 138 min at pH 4.5. The colchicine-cobalamin bioconjugate exhibits nanomolar LC50 values against breast, brain, and melanoma cancer cell lines in culture. Attachment of colchicine to cobalamin is expected to increase the therapeutic index of the drug by limiting the side effects caused by the current nonselective administration of tubulin-targeted chemotherapeutic drugs.
• Sialic Acid Derivatives
  申请人：Brossmer Reinhard

  公开号：US20150174262A1

  公开（公告）日：2015-06-25

  A sialic acid derivative of the formula (I), where the symbols are as defined in the description, is suitable for linking with a cargo for regulating metabolic processes, immune reactions, immunizations or desensitizations of the target organism.

  公式（I）的唾液酸衍生物，其中符号如描述中定义的那样，适用于与一种货物连接，用于调节目标生物体的代谢过程、免疫反应、免疫或脱敏。