| 382601-31-2

• CAS: 382601-31-2
• 化学式: C₅₂H₅₉NO₁₅S
• 分子量: 970.104
• InChiKey: YBBFQHISGDZKPN-PRAKAINVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.39
• 重原子数：
  69.0
• 可旋转键数：
  13.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  227.36
• 氢给体数：
  4.0
• 氢受体数：
  16.0

反应信息

• 作为反应物：
  描述：

  在 亚硝酸特丁酯 作用下， 以 二氯甲烷 为溶剂， 反应 0.25h， 以89%的产率得到[(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-diacetyloxy-15-[(2R,3S)-3-benzamido-2-hydroxy-3-phenylpropanoyl]oxy-1-hydroxy-10,14,17,17-tetramethyl-9-(3-methyl-3-nitrososulfanylbutanoyl)oxy-11-oxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate
  参考文献：
  名称：

  Combination of Paclitaxel and Nitric Oxide as a Novel Treatment for the Reduction of Restenosis

  摘要：

  The combination of a nitric oxide (NO) donor and a paclitaxel-NO donor conjugate coated on a vascular stent was tested in a rabbit iliac artery model of stenosis as a potential therapy for restenosis. Paclitaxel was conjugated with a NO donor at the 7-position to give compound 7. An adamantane-based NO donor 14 was synthesized and combined with 7 to provide a burst of NO in the first few critical hours following injury to the vessel wall. Both 7 and 14 demonstrated antiproliferative activity (IC50 = 20 nM and 15 muM, respectively) and antiplatelet activity (IC50 = 10 and 1 muM, respectively). Stents were coated with a layer of a polymer containing test compounds. The total amount of NO eluted from the stents after a 6 h implantation in the rabbit iliac artery was 35,70, 95%, and 69% of the original content for the stents coated with 7, 14, and the combination of 7 and 14, respectively. The antistenotic activity of 7 and 14 was determined in a 28-day rabbit model with two control groups (uncoated stents and polymer-coated stents) and two study groups (paclitaxel-coated stents and stents coated with the combination of 7 and 14). Polymer-coated stents caused inflammation and increased stenosis by 39% when compared to the uncoated stents. The stents coated with 7 plus 14 were as good as the uncoated stents, 41% better than the polymer-coated stents and 34% better than the paclitaxel-coated stents. These data indicate a beneficial effect of adding NO to an antiproliferative agent (paclitaxel) and suggest a potential therapeutic combination for the treatment of stenotic vessel disease.

  DOI：

  10.1021/jm0304111
• 作为产物：
  描述：

  2'-(2,2,2-trichloroethoxycarbonyl)-7-[3-methyl-3-(2,4,6-trimethoxyphenylmethylsulfanyl)butyryl]paclitaxel 在 甲酸 、 L-半胱氨酸 、 溶剂黄146 、 锌 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 3.0h， 生成
  参考文献：
  名称：

  Combination of Paclitaxel and Nitric Oxide as a Novel Treatment for the Reduction of Restenosis

  摘要：

  The combination of a nitric oxide (NO) donor and a paclitaxel-NO donor conjugate coated on a vascular stent was tested in a rabbit iliac artery model of stenosis as a potential therapy for restenosis. Paclitaxel was conjugated with a NO donor at the 7-position to give compound 7. An adamantane-based NO donor 14 was synthesized and combined with 7 to provide a burst of NO in the first few critical hours following injury to the vessel wall. Both 7 and 14 demonstrated antiproliferative activity (IC50 = 20 nM and 15 muM, respectively) and antiplatelet activity (IC50 = 10 and 1 muM, respectively). Stents were coated with a layer of a polymer containing test compounds. The total amount of NO eluted from the stents after a 6 h implantation in the rabbit iliac artery was 35,70, 95%, and 69% of the original content for the stents coated with 7, 14, and the combination of 7 and 14, respectively. The antistenotic activity of 7 and 14 was determined in a 28-day rabbit model with two control groups (uncoated stents and polymer-coated stents) and two study groups (paclitaxel-coated stents and stents coated with the combination of 7 and 14). Polymer-coated stents caused inflammation and increased stenosis by 39% when compared to the uncoated stents. The stents coated with 7 plus 14 were as good as the uncoated stents, 41% better than the polymer-coated stents and 34% better than the paclitaxel-coated stents. These data indicate a beneficial effect of adding NO to an antiproliferative agent (paclitaxel) and suggest a potential therapeutic combination for the treatment of stenotic vessel disease.

  DOI：

  10.1021/jm0304111