N-de-tert-butoxycarbonyl-N-[2-(1-fluoro-2-methyl)-propyloxycarbonyl]docetaxel | 947600-16-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: N-de-tert-butoxycarbonyl-N-[2-(1-fluoro-2-methyl)-propyloxycarbonyl]docetaxel
• 英文别名: [(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-acetyloxy-15-[(2R,3S)-3-[(1-fluoro-2-methylpropan-2-yl)oxycarbonylamino]-2-hydroxy-3-phenylpropanoyl]oxy-1,9,12-trihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate
• CAS: 947600-16-0
• 化学式: C₄₃H₅₂FNO₁₄
• 分子量: 825.883
• InChiKey: HQZCJRMVMTZZIB-VCVYQWHSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  59
• 可旋转键数：
  14
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  224
• 氢给体数：
  5
• 氢受体数：
  15

反应信息

• 作为产物：
  描述：

  N-de-tert-butoxycarbonyl-N-[2-(1-fluoro-2-methyl)-propyloxycarbonyl]-7,10-di(2,2,2-trichloroethyloxycarbonyl)-docetaxel 在 溶剂黄146 、 锌 作用下， 以 甲醇 为溶剂， 反应 0.5h， 以81%的产率得到N-de-tert-butoxycarbonyl-N-[2-(1-fluoro-2-methyl)-propyloxycarbonyl]docetaxel
  参考文献：
  名称：

  Design, synthesis and biological evaluation of novel fluorinated docetaxel analogues

  摘要：

  A series of novel fluorinated docetaxel analogues have been synthesized and evaluated in vitro and in vivo. Incorporated one, two or three fluorine atom(s) either at both meta position on C-2 benzolate and 3'-N-tert-butyloxyl group or only at 3-N-tert-butyloxyl group has resulted in potent analogues which have comparable or superior in vitro and in vivo cytotoxicity to docetaxel. Among them, compounds 14d and 14e have displayed more potent cytotoxicity than docetaxel both in human cancer cell line SK-OV-3 in vitro and in human non-small cell lung cancer A549 xenografts in vivo. Preliminary data show that compound 14a has reduced acute animal toxicity in mice compared with docetaxel. (C) 2008 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2008.04.004

文献信息

• Design, synthesis and biological evaluation of novel fluorinated docetaxel analogues
  作者：Hong-Fu Lu、Xun Sun、Liang Xu、Li-Guang Lou、Guo-Qiang Lin

  DOI：10.1016/j.ejmech.2008.04.004

  日期：2009.2

  A series of novel fluorinated docetaxel analogues have been synthesized and evaluated in vitro and in vivo. Incorporated one, two or three fluorine atom(s) either at both meta position on C-2 benzolate and 3'-N-tert-butyloxyl group or only at 3-N-tert-butyloxyl group has resulted in potent analogues which have comparable or superior in vitro and in vivo cytotoxicity to docetaxel. Among them, compounds 14d and 14e have displayed more potent cytotoxicity than docetaxel both in human cancer cell line SK-OV-3 in vitro and in human non-small cell lung cancer A549 xenografts in vivo. Preliminary data show that compound 14a has reduced acute animal toxicity in mice compared with docetaxel. (C) 2008 Elsevier Masson SAS. All rights reserved.
• Design, synthesis and cytotoxicity of novel 3′-N-alkoxycarbonyl docetaxel analogs
  作者：Jun Chang、Xiao-Dong Hao、Yun-Peng Hao、Hong-Fu Lu、Jian-Ming Yu、Xun Sun

  DOI：10.1016/j.bmcl.2013.10.007

  日期：2013.12

  By-product 9a exhibited potent cytotoxicity against both SK-OV-3 and A549 cell lines. The structure of 9a was characterized using 1D and 2D NMR experiments and confirmed by synthesis to afford a diastereomeric mixture (16a) that was identical to 9a, as well as a pair of diastereomers (R)-16b and (S)-16c. The preliminary SAR study demonstrated that analogs with an (R)-configuration were slightly more potent than analogs with an (S)-configuration. In addition, alpha, alpha-gem-dimethyl analogs 16g-i were the most potent analogs in this series, exhibiting similar potency to docetaxel and greater potency than Taxol against the SK-OV-3 cell line. For the A549 cell line, analogs 16g-i were more potent (>65-fold) than both docetaxel and Taxol. (C) 2013 Elsevier Ltd. All rights reserved.