(3R,4S)-1-benzoyl-3-triisopropylsilyloxy-4-(2-methylprop-1-enyl)azetidin-2-one | 618427-94-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: (3R,4S)-1-benzoyl-3-triisopropylsilyloxy-4-(2-methylprop-1-enyl)azetidin-2-one
• CAS: 618427-94-4
• 化学式: C₂₃H₃₅NO₃Si
• 分子量: 401.621
• InChiKey: LFVSXTXSEKOIDL-LEWJYISDSA-N

物化性质

• 沸点：
  451.0±55.0 °C(Predicted)
• 密度：
  1.03±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.56
• 重原子数：
  28.0
• 可旋转键数：
  7.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  46.61
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (3R,4S)-1-benzoyl-3-triisopropylsilyloxy-4-(2-methylprop-1-enyl)azetidin-2-one 在 吡啶 、 氢氟酸 、 sodium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 3.5h， 生成 SB-T-1212N1
  参考文献：
  名称：

  Structure–activity relationship study of taxoids for their ability to activate murine macrophages as well as inhibit the growth of macrophage-like cells

  摘要：

  A series of new taxoids modified at the C-3', C-3'N, C-10, C-2 and C-7 positions has been designed, synthesized and evaluated for their potency to induce NO and TNF production by peritoneal murine macrophages (Mphi) from LPS-responsive C3H/HeN and LPS-hyporesponsive C3H/HeJ strains and human blood cells, and for their ability to inhibit the growth of Mphi-like cell lines J774.1 and J7.DEF3. The SAR-study has shown that the nature of the substituents at these positions have critical effect on the induction of TNF and NO production by Mphi. Positions G-3' and C-10 are the most flexible and an intriguing effect of the length of the substituents at the C-10 position is observed for taxoids bearing a straight chain alkanoyl moiety. An aromatic group at the C-3'N and C-2 positions is required for the activity, while only hydroxyl or acetyl substituents seem to be tolerated at the C-7 position. The natural stereochemistry in the C-13 isoserine side chain of the taxoids is an absolute requirement for macrophage activation. It has also been clearly shown that there is no correlation between the ability of the taxoids to induce TNF/NO production in C3H/HeN M and the cytotoxicity against Mphi-like cells. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00181-0
• 作为产物：
  描述：

  在 4-二甲氨基吡啶 、 ammonium cerium(IV) nitrate 、 三乙胺 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 反应 3.0h， 生成 (3R,4S)-1-benzoyl-3-triisopropylsilyloxy-4-(2-methylprop-1-enyl)azetidin-2-one
  参考文献：
  名称：

  Structure–activity relationship study of taxoids for their ability to activate murine macrophages as well as inhibit the growth of macrophage-like cells

  摘要：

  A series of new taxoids modified at the C-3', C-3'N, C-10, C-2 and C-7 positions has been designed, synthesized and evaluated for their potency to induce NO and TNF production by peritoneal murine macrophages (Mphi) from LPS-responsive C3H/HeN and LPS-hyporesponsive C3H/HeJ strains and human blood cells, and for their ability to inhibit the growth of Mphi-like cell lines J774.1 and J7.DEF3. The SAR-study has shown that the nature of the substituents at these positions have critical effect on the induction of TNF and NO production by Mphi. Positions G-3' and C-10 are the most flexible and an intriguing effect of the length of the substituents at the C-10 position is observed for taxoids bearing a straight chain alkanoyl moiety. An aromatic group at the C-3'N and C-2 positions is required for the activity, while only hydroxyl or acetyl substituents seem to be tolerated at the C-7 position. The natural stereochemistry in the C-13 isoserine side chain of the taxoids is an absolute requirement for macrophage activation. It has also been clearly shown that there is no correlation between the ability of the taxoids to induce TNF/NO production in C3H/HeN M and the cytotoxicity against Mphi-like cells. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00181-0

文献信息

• Synthesis and biological evaluation of novel taxoids designed for targeted delivery to tumors
  作者：Erkan Baloglu、Michael L. Miller、Elizabeth E. Roller、Emily E. Cavanagh、Barbara A. Leece、Victor S. Goldmacher、Ravi V.J. Chari

  DOI：10.1016/j.bmcl.2004.09.025

  日期：2004.12

  they are capable of targeting tumor markers selectively. We have prepared taxoids with significantly higher cytotoxicity than paclitaxel and docetaxel. These taxoids now meet the high potency required for use in a targeted-delivery approach using monoclonal antibodies. The synthesis and biological evaluation of these taxoids are reported.

  药物-抗体缀合物的使用提供了将抗癌药物靶向递送至癌细胞的方法。单独的单克隆抗体通常不具有很高的治疗功效，但是，它们能够选择性地靶向肿瘤标志物。我们准备了比紫杉醇和多西紫杉醇具有明显更高细胞毒性的紫杉烷类药物。现在，这些类紫杉醇可满足使用单克隆抗体进行靶向递送方法所需的高效力。报告了这些类紫杉醇的合成和生物学评估。