Compound (3)

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: Compound (3)
• 英文别名: 6-ethyl-2-sulfanylidene-5-tetradecyl-1H-pyrimidin-4-one
• 化学式: C₂₀H₃₆N₂OS
• 分子量: 352.585
• InChiKey: OHHXAUDEKUJJIA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.7
• 重原子数：
  24
• 可旋转键数：
  14
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  73.2
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  Compound (3) 在 氯乙酸 作用下， 以 水 为溶剂， 反应 12.0h， 以38%的产率得到Compound (4)
  参考文献：
  名称：

  Ceramide analogs, process for their preparation and their use as antitumor agents

  摘要：

  本发明涉及一般式(I)的神经酰胺类似化合物，其制备方法以及用于制备用于治疗肿瘤的药物配方的用途。

  公开号：

  US20050020533A1
• 作为产物：
  描述：

  棕榈酸乙酯 在 sodium ethanolate 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 13.5h， 生成 Compound (3)
  参考文献：
  名称：

  Design, Synthesis, and Characterization of the Antitumor Activity of Novel Ceramide Analogues

  摘要：

  A deficiency in apoptosis is one of the key events in the proliferation and resistance of malignant cells to antitumor agents; for these reasons, the search for apoptosis-inducing drugs represents a valuable approach for the development of novel anticancer therapies. In this study we report the first example of conformationally restrained analogues of ceramide (compounds 1-4), where the polar portion of the molecule has been replaced by a thiouracil (1, 3) or uracil (2, 4) ring. The evaluation of their biologic activity on CCRF-CEM human leukemia cells demonstrated that the most active was compound 1 followed by compound 2 (mean 50% inhibition of cell proliferation [IC50] 1.7 and 7.9 PM, respectively), while compounds 3 and 4 were inactive, as were uracil, thiouracil, and 5,6-dimethyluracil, the pyrimidine moieties of compounds 1-4. For comparison, the IC50 of the reference substance, the cell-permeable C-2-ceramide, was 31.6 muM. Compounds 1 and 2 and C-2-ceramide were able to trigger apoptosis, as shown by the occurrence of DNA and nuclear fragmentation, and to release cytochrome c from treated cells. The treatment of female CD-1 nu/nu athymic mice bearing a WiDr human colon xenograft with the most active compound 1 at 2, 10, 50, and 200 mg/kg ip daily for 10 days resulted in an antitumor effect that was equivalent at 50 mg/kg or superior (200 mg/kg) to that of cyclophosphamide, 20 mg/kg ip daily, delivered on the same schedule, with markedly lower systemic toxicity. In conclusion, the present study demonstrates that the new ceramide analogues 1 and 2 are characterized by in vitro and in vivo antitumor activity and low toxicity.

  DOI：

  10.1021/jm010947r
• 作为试剂：
  描述：

  柠檬醛 在 Compound (3) 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 0.58h， 生成 橙花醇
  参考文献：
  名称：

  一种衍生自甲酸和两当量格氏试剂的新型还原剂：醛的化学选择性还原

  摘要：

  通过使用通过在四氢呋喃溶液中将两个摩尔当量的乙基溴化镁添加到甲酸中而获得的新型试剂，以中等速率还原醛。在相似的条件下，酮的还原过程非常缓慢。

  DOI：

  10.1016/s0040-4039(01)92505-5

文献信息

• Ceramide analogs, process for their preparation and their use as antitumor agents
  申请人：Macchia Bruno

  公开号：US20050020533A1

  公开（公告）日：2005-01-27

  The present invention is directed to ceramide analog compounds of general formula (I) the process for their preparation and use for the preparation of pharmaceutical formulations for the treatment of tumors.

  本发明涉及一般式(I)的神经酰胺类似化合物，其制备方法以及用于制备用于治疗肿瘤的药物配方的用途。
• Design, Synthesis, and Characterization of the Antitumor Activity of Novel Ceramide Analogues
  作者：Marco Macchia、Silvia Barontini、Simone Bertini、Valeria Di Bussolo、Stefano Fogli、Elisa Giovannetti、Enzo Grossi、Filippo Minutolo、Romano Danesi

  DOI：10.1021/jm010947r

  日期：2001.11.1

  A deficiency in apoptosis is one of the key events in the proliferation and resistance of malignant cells to antitumor agents; for these reasons, the search for apoptosis-inducing drugs represents a valuable approach for the development of novel anticancer therapies. In this study we report the first example of conformationally restrained analogues of ceramide (compounds 1-4), where the polar portion of the molecule has been replaced by a thiouracil (1, 3) or uracil (2, 4) ring. The evaluation of their biologic activity on CCRF-CEM human leukemia cells demonstrated that the most active was compound 1 followed by compound 2 (mean 50% inhibition of cell proliferation [IC50] 1.7 and 7.9 PM, respectively), while compounds 3 and 4 were inactive, as were uracil, thiouracil, and 5,6-dimethyluracil, the pyrimidine moieties of compounds 1-4. For comparison, the IC50 of the reference substance, the cell-permeable C-2-ceramide, was 31.6 muM. Compounds 1 and 2 and C-2-ceramide were able to trigger apoptosis, as shown by the occurrence of DNA and nuclear fragmentation, and to release cytochrome c from treated cells. The treatment of female CD-1 nu/nu athymic mice bearing a WiDr human colon xenograft with the most active compound 1 at 2, 10, 50, and 200 mg/kg ip daily for 10 days resulted in an antitumor effect that was equivalent at 50 mg/kg or superior (200 mg/kg) to that of cyclophosphamide, 20 mg/kg ip daily, delivered on the same schedule, with markedly lower systemic toxicity. In conclusion, the present study demonstrates that the new ceramide analogues 1 and 2 are characterized by in vitro and in vivo antitumor activity and low toxicity.
• Ceramide analogues in apoptosis: a new strategy for anticancer drug development
  作者：Marco Macchia、Simone Bertini、Stefano Fogli、Elisa Giovannetti、Filippo Minutolo、Simona Rapposelli、Romano Danesi

  DOI：10.1016/s0014-827x(03)00015-6

  日期：2003.3

  A survey on the role played by ceramide within the sphingolmyelin pathway is here reported, taking into account its importance as an intracellular effector molecule in apoptosis. Recently, several analogs of ceramide, able to pass the cell membrane and then to induce apoptosis, have been developed as a new potential approach in anticancer therapy.