| 146307-39-3

• CAS: 146307-39-3
• 化学式: C₅₁H₅₅NO₁₆
• 分子量: 937.995
• InChiKey: MERHQRHHYQXFHT-CEPOORRRSA-N

物化性质

• 沸点：
  977.9±65.0 °C(Predicted)
• 密度：
  1.37±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.08
• 重原子数：
  68.0
• 可旋转键数：
  13.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  236.59
• 氢给体数：
  3.0
• 氢受体数：
  16.0

反应信息

• 作为反应物：
  描述：

  在 四(三苯基膦)钯 4-二甲氨基吡啶 、 苯硅烷 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 11.0h， 生成
  参考文献：
  名称：

  Synthesis and Evaluation of Taxol–Folic Acid Conjugates as Targeted Antineoplastics † †See ref 1.

  摘要：

  A series of Taxol derivatives tethered at C2' and C-7 to glutamate and folate have been synthesized for evaluation as prodrugs which release Taxol via hydrolytic lability of their alpha-alkoxy and alpha-amino esters. The half-time for hydrolysis of these materials was determined in pH 7 and pH 5 buffer. The in vitro cytotoxicity has been assessed in cell culture against A-549 lung cancer, MCF-7 breast cancer, and HT-29 colon cancer. Selected agents were further screened for folate binding and competitive binding with free folic acid, One agent (54), further evaluated in animal Studies as found to increase the lifespan in mice, but was less effective than Taxol itself. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00019-6
• 作为产物：
  描述：

  紫杉醇 、 氯甲酸烯丙酯 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 10.0h， 以98%的产率得到
  参考文献：
  名称：

  Synthesis and Evaluation of Taxol–Folic Acid Conjugates as Targeted Antineoplastics † †See ref 1.

  摘要：

  A series of Taxol derivatives tethered at C2' and C-7 to glutamate and folate have been synthesized for evaluation as prodrugs which release Taxol via hydrolytic lability of their alpha-alkoxy and alpha-amino esters. The half-time for hydrolysis of these materials was determined in pH 7 and pH 5 buffer. The in vitro cytotoxicity has been assessed in cell culture against A-549 lung cancer, MCF-7 breast cancer, and HT-29 colon cancer. Selected agents were further screened for folate binding and competitive binding with free folic acid, One agent (54), further evaluated in animal Studies as found to increase the lifespan in mice, but was less effective than Taxol itself. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00019-6

文献信息

• Design and synthesis of releasable folate–drug conjugates using a novel heterobifunctional disulfide-containing linker
  作者：Apparao Satyam

  DOI：10.1016/j.bmcl.2008.04.063

  日期：2008.6

  Cellular uptake of vitamin folic acid occurs via folate-receptor mediated endocytosis. Many types of cancer cells express high levels of folate receptors as they need continuous supply of this vitamin for their proliferation. With an objective to use folic acid as a 'Trojan Horse' to transport anticancer drugs into cancer cells, a novel heterobifunctional disulfide-containing linker was synthesized and utilized to covalently link an amino-and hydroxyl-containing anticancer drug, and an appropriately functionalized folic acid to create novel targetable folate-drug conjugates that are shown to release free drugs under biologically relevant pH via sulfhydryl-assisted cleavage of the self-immolative disulfide-containing linker. (C) 2008 Elsevier Ltd. All rights reserved.