10-propanoyl-3'-dephenyl-3'-(2-methylprop-1-enyl)-3'N-(cyclopentanecarbonyl)docetaxel | 1031784-19-6

• 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: 10-propanoyl-3'-dephenyl-3'-(2-methylprop-1-enyl)-3'N-(cyclopentanecarbonyl)docetaxel
• 英文别名: [(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-acetyloxy-15-[(2R,3S)-3-(cyclopentanecarbonylamino)-2-hydroxy-5-methylhex-4-enoyl]oxy-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-12-propanoyloxy-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate
• CAS: 1031784-19-6
• 化学式: C₄₅H₅₉NO₁₄
• 分子量: 837.962
• InChiKey: NHKJPFYCUJUOEN-PHGMAVRCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  60
• 可旋转键数：
  15
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  221
• 氢给体数：
  4
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  10-propanoyl-3'-dephenyl-3'-(2-methylprop-1-enyl)-3'N-(cyclopentanecarbonyl)docetaxel 在 10% Pd on charcoal 、 氢气 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 反应 24.0h， 以100%的产率得到10-propanoyl-3'-dephenyl-3'-(2-methylpropyl)-3'N-debenzoyl-3'N-(cyclopentanecarbonyl)docetaxel
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of New-Generation Taxoids

  摘要：

  Novel second-generation taxoids with systematic modifications at the C2, C10, and C3'N positions were synthesized and their structure-activity relationships studied. A number of these taxoids exhibited exceptionally high potency against multidrug-resistant cell lines, and several taxoids exhibited virtually no difference in potency against the drug-sensitive and drug-resistant cell lines. These exceptionally potent taxoids were termed "third-generation taxoids". 19 (SB-T-1214), 14g(SB-T-121303), and 14i (SB-T-1213031) exhibited excellent activity against paclitaxel-resistant ovarian cancer cell lines with mutations in beta-tubulin as well, wherein the drug resistance is mediated by the beta-tubulin mutation. These taxoids were found to possess exceptional activity in promoting tubulin assembly, forming numerous very short microtubules similar to those formed by discodermolide. Taxoids 19 and 14g also showed excellent cytotoxicity against four pancreatic cancer cell lines, expressing three to four multidrug-resistant genes. Moreover, taxoid 19 exhibited excellent in vivo efficacy against highly drug-resistant CFPAC-1 pancreatic as well as DLD-1 human colon tumor xenografts in mice.

  DOI：

  10.1021/jm800086e
• 作为产物：
  描述：

  在 吡啶 、 氟化氢吡啶 作用下， 以 乙腈 为溶剂， 反应 18.0h， 生成 10-propanoyl-3'-dephenyl-3'-(2-methylprop-1-enyl)-3'N-(cyclopentanecarbonyl)docetaxel
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of New-Generation Taxoids

  摘要：

  Novel second-generation taxoids with systematic modifications at the C2, C10, and C3'N positions were synthesized and their structure-activity relationships studied. A number of these taxoids exhibited exceptionally high potency against multidrug-resistant cell lines, and several taxoids exhibited virtually no difference in potency against the drug-sensitive and drug-resistant cell lines. These exceptionally potent taxoids were termed "third-generation taxoids". 19 (SB-T-1214), 14g(SB-T-121303), and 14i (SB-T-1213031) exhibited excellent activity against paclitaxel-resistant ovarian cancer cell lines with mutations in beta-tubulin as well, wherein the drug resistance is mediated by the beta-tubulin mutation. These taxoids were found to possess exceptional activity in promoting tubulin assembly, forming numerous very short microtubules similar to those formed by discodermolide. Taxoids 19 and 14g also showed excellent cytotoxicity against four pancreatic cancer cell lines, expressing three to four multidrug-resistant genes. Moreover, taxoid 19 exhibited excellent in vivo efficacy against highly drug-resistant CFPAC-1 pancreatic as well as DLD-1 human colon tumor xenografts in mice.

  DOI：

  10.1021/jm800086e