6-O-(2-carboxybenzoyl)fumagillol | 129298-89-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 6-O-(2-carboxybenzoyl)fumagillol
• 英文别名: 2-[[(3R,4S,5S,6R)-5-methoxy-4-[(2R,3R)-2-methyl-3-(3-methylbut-2-enyl)oxiran-2-yl]-1-oxaspiro[2.5]octan-6-yl]oxycarbonyl]benzoic acid
• CAS: 129298-89-1
• 化学式: C₂₄H₃₀O₇
• 分子量: 430.498
• InChiKey: ATLFJRVECCHYFQ-LQCNHDFWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  97.9
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  6-O-(2-carboxybenzoyl)fumagillol 在 溶剂黄146 、 lithium chloride 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 生成 7-chloro-6-[(2-carboxybenzoyl)oxy]-fumagillol
  参考文献：
  名称：

  Synthesis and antiproliferative activity of ligerin and new fumagillin analogs against osteosarcoma

  摘要：

  Ligerin (1) is a natural chlorinated merosesquiterpenoid related to fumagillin (2) exhibiting a selective antiproliferative activity against osteosarcoma cell lines and an in vivo antitumor activity in a murine model. Semisynthesis of ligerin analogs was performed in order to study the effects of the C3-spiroepoxide substitution by a halogenated moiety together with the modulation of the C6 chain. Results showed that all derivatives exhibited an in vitro antiproliferative activity against osteosarcoma cell lines and that chlorohydrin compounds were equally or more active than their spiroepoxy analogs. Among semisynthetic analogs, the parent compound 1 was the best candidate for further studies since it exhibited higher or equivalent activity compared to TNP470 (3) against SaOS2 and MG63 human osteosarcoma cells with a four times weaker toxicity against HFF2 human fibroblasts. Quantitative videomicroscopy analysis was conducted and allowed a better understanding of the mechanism of its antiproliferative activity. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.04.012
• 作为产物：
  描述：

  烟曲霉素 在 吡啶 、 4-二甲氨基吡啶 、 sodium hydroxide 作用下， 反应 42.0h， 生成 6-O-(2-carboxybenzoyl)fumagillol
  参考文献：
  名称：

  Synthesis and antiproliferative activity of ligerin and new fumagillin analogs against osteosarcoma

  摘要：

  Ligerin (1) is a natural chlorinated merosesquiterpenoid related to fumagillin (2) exhibiting a selective antiproliferative activity against osteosarcoma cell lines and an in vivo antitumor activity in a murine model. Semisynthesis of ligerin analogs was performed in order to study the effects of the C3-spiroepoxide substitution by a halogenated moiety together with the modulation of the C6 chain. Results showed that all derivatives exhibited an in vitro antiproliferative activity against osteosarcoma cell lines and that chlorohydrin compounds were equally or more active than their spiroepoxy analogs. Among semisynthetic analogs, the parent compound 1 was the best candidate for further studies since it exhibited higher or equivalent activity compared to TNP470 (3) against SaOS2 and MG63 human osteosarcoma cells with a four times weaker toxicity against HFF2 human fibroblasts. Quantitative videomicroscopy analysis was conducted and allowed a better understanding of the mechanism of its antiproliferative activity. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.04.012

文献信息

• Chemical Modification of Fumagillin. I. 6-O-Acyl, 6-O-Sulfonyl, 6-O-Alkyl, and 6-O-(N-Substituted-carbamoyl)fumagillols.
  作者：Shogo MARUI、Fumio ITOH、Yoshio KOZAI、Katsuichi SUDO、Shoji KISHIMOTO

  DOI：10.1248/cpb.40.96

  日期：——

  The hydroxy group of fumagillol (3), a degradation product of fumagillin (1), was acylated, sulfonylated, alkylated or carbamoylated, and the anti-angiogenic activity of the resulting products was examined. These compounds inhibited the angiogenesis induced by basic fibroblast growth factor in the rat corneal micropocket assay and the growth of vascular endothelial cells in vitro. Among them, compound 2 (AGM-1470) was found to show the most potent inhibitory effect on the growth of vascular endothelial cells and was selected form this series as a candidate for further development.

  烟曲霉素（1）的降解产物烟曲霉醇（3）的羟基被酰化、磺酰化、烷基化或氨基甲酰化，并考察了所得产物的抗血管生成活性。这些化合物抑制了在大鼠角膜微囊中由碱性成纤维细胞生长因子诱导的血管生成以及体外血管内皮细胞的生长。其中，化合物2（AGM-1470）被发现对血管内皮细胞生长具有最强的抑制作用，并被选为这一系列的候选药物进一步开发。
• Synthesis and antiproliferative activity of ligerin and new fumagillin analogs against osteosarcoma
  作者：Elodie Blanchet、Marieke Vansteelandt、Ronan Le Bot、Maxim Egorov、Yann Guitton、Yves François Pouchus、Olivier Grovel

  DOI：10.1016/j.ejmech.2014.04.012

  日期：2014.5

  Ligerin (1) is a natural chlorinated merosesquiterpenoid related to fumagillin (2) exhibiting a selective antiproliferative activity against osteosarcoma cell lines and an in vivo antitumor activity in a murine model. Semisynthesis of ligerin analogs was performed in order to study the effects of the C3-spiroepoxide substitution by a halogenated moiety together with the modulation of the C6 chain. Results showed that all derivatives exhibited an in vitro antiproliferative activity against osteosarcoma cell lines and that chlorohydrin compounds were equally or more active than their spiroepoxy analogs. Among semisynthetic analogs, the parent compound 1 was the best candidate for further studies since it exhibited higher or equivalent activity compared to TNP470 (3) against SaOS2 and MG63 human osteosarcoma cells with a four times weaker toxicity against HFF2 human fibroblasts. Quantitative videomicroscopy analysis was conducted and allowed a better understanding of the mechanism of its antiproliferative activity. (C) 2014 Elsevier Masson SAS. All rights reserved.