3-isopropyl-2-methyl-4-methyleneisoxazolidin-5-one | 880480-25-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: 3-isopropyl-2-methyl-4-methyleneisoxazolidin-5-one
• 英文别名: MZ-6；5-Isoxazolidinone, 2-methyl-4-methylene-3-(1-methylethyl)-；2-methyl-4-methylidene-3-propan-2-yl-1,2-oxazolidin-5-one
• CAS: 880480-25-1
• 化学式: C₈H₁₃NO₂
• 分子量: 155.197
• InChiKey: SNHIHYMJDYSGHP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  ethyl 2-(diethoxyphosphoryl)acrylate 在 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 20.75h， 生成 3-isopropyl-2-methyl-4-methyleneisoxazolidin-5-one
  参考文献：
  名称：

  4-Methylideneisoxazolidin-5-ones—A new class of α-methylidene-γ-lactones with high cytostatic activity

  摘要：

  A novel, general method of synthesis of 4-methylideneisoxazolidin-5-ones 10 is described. The target compounds were synthesized starting from ethyl 2-diethoxyphosphoryl-2-alkenoates 6 or dicyclohexylammonium 4-diethoxyphosphoryl-2-alkenoates 7. Addition of N-methylhydroxylamine hydrochloride to these Michael acceptors, lactonization to 4-diethoxyphosphorylisoxazolidin-5-ones 9, and Horner-Wadsworth-Emmons olefination of formaldehyde using 9 gave the title isoxazolidinones 10. All obtained compounds were tested against L-1210, HL-60, and NALM-6 leukemia cell lines. Several isoxazolidinones 10 were found to be very potent with IC50 < 1 mu M. The highest cytostatic activity against HL-60 was observed for 10a and against NALM-6 for 10b with IC50 values of 0.74 and 0.34 mu M, respectively. (C) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.11.032

文献信息

• Comparison of Anti-Invasive Activity of Parthenolide and 3-Isopropyl-2-Methyl-4-Methyleneisoxazolidin-5-One (MZ-6) - A New Compound with α-Methylene-γ-Lactone Motif - on Two Breast Cancer Cell Lines
  作者：Anna Wyrębska、Katarzyna Gach、Janusz Szemraj、Karolina Szewczyk、Elżbieta Hrabec、Jacek Koszuk、Tomasz Janecki、Anna Janecka

  DOI：10.1111/j.1747-0285.2011.01257.x

  日期：2012.1

  present study, we describe an efficient method of preparation of 3‐isopropyl‐2‐methyl‐4‐methyleneisoxazolidin‐5‐one (MZ‐6), a synthetic compound with α‐methylene‐γ‐lactone ring, as in parthenolide, additionally modified by introduction of a nitrogen atom. Furthermore, we investigated the cytotoxic activity and anti‐metastatic potential of MZ‐6 in comparison with parthenolide. Both compounds showed considerable

  从小白菊中分离出的倍半萜内酯Parthenolide的生物活性归因于α-亚甲基-γ-内酯骨架的存在。内酯骨架可以通过带有酶和其他功能蛋白的巯基的迈克尔型加成，干扰细胞中的关键生物学过程。在本研究中，我们描述了一种高效的制备3-异丙基-2-甲基-4-亚甲基异恶唑啉丁-5-酮（MZ-6）的有效方法，该合成化合物具有α-亚甲基-γ-内酯环，如小白菊内酯。 ，另外通过引入氮原子进行修饰。此外，我们研究了MZ-6与Parthenolide相比的细胞毒性活性和抗转移潜力。两种化合物在体外均对乳腺癌MCF-7和MDA-MB-231腺癌细胞具有相当大的细胞毒性然后评估其抗转移潜力。实验结果表明，MZ-6和小白菊内酯在相同程度上抑制了MCF-7的迁移，但对更具侵略性的MDA-MB-231细胞却没有抑制。在这两种细胞系中，测试的化合物均下调了金属蛋白酶9和尿激酶纤溶酶原激活剂的mRNA和蛋白水平，这是参与细胞