2-debenzoyl-2-(3-chlorobenzoyl)-10-acetyl-3'-dephenyl-3'-difluoromethyldocetaxel | 1134619-02-5

• 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: 2-debenzoyl-2-(3-chlorobenzoyl)-10-acetyl-3'-dephenyl-3'-difluoromethyldocetaxel
• 英文别名: [(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-diacetyloxy-15-[(2R,3R)-4,4-difluoro-2-hydroxy-3-[(2-methylpropan-2-yl)oxycarbonylamino]butanoyl]oxy-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] 3-chlorobenzoate
• CAS: 1134619-02-5
• 化学式: C₄₀H₅₀ClF₂NO₁₅
• 分子量: 858.285
• InChiKey: AMDOBHSHICFEKU-CWRKUANCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  59
• 可旋转键数：
  15
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  231
• 氢给体数：
  4
• 氢受体数：
  17

反应信息

• 作为产物：
  描述：

  在 pyridine hydrofluoride 作用下， 以 吡啶 、 乙腈 为溶剂， 生成 2-debenzoyl-2-(3-chlorobenzoyl)-10-acetyl-3'-dephenyl-3'-difluoromethyldocetaxel
  参考文献：
  名称：

  Syntheses and structure–activity relationships of novel 3′-difluoromethyl and 3′-trifluoromethyl-taxoids

  摘要：

  A series of novel 3'-difluoromethyl-taxoids and 3'-trifluoromethyl-taxoids with modifications at the C2 and C10 positions were synthesized and evaluated for their in vitro cytotoxicities against human breast carcinoma (MCF7-S, MCF7-R, LCC6-WT, LCC6-MDR), non-small cell lung carcinoma (H460) and colon adenocarcinoma (HT-29) cell lines. These second-generation fluoro-taxoids exhibited several times to more than 20 times better potency than paclitaxel against drug-sensitive cancer cell lines, MCF7-S, LCC6-WT. H460, and HT-29. These fluoro-taxoids also possess two orders of magnitude higher potency than paclitaxel against drug-resistant cancer cell lines, MCF7-R and LCC6-MDR. Structure-activity relationship study shows the importance of the C10 modification for increasing the activity against multidrug-resistant cancer cell lines. Effects of the C2-benzoate modifications on the potency in the 3'-difluoromethyl-taxoid series are very clear- (i.e., F < MeO < Cl < N-3), while those in the 3'-trifluoromethyl-taxoid series are less obvious. Also, different trends in the sensitivity to the C2-substitution are observed between drug-sensitive cell lines and drug-resistant cancer cell lines that overexpress efflux pumps. (c) 2008 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.jfluchem.2008.05.013