tert-butyl 3-benzyl-6,6a-dihydro-3aH-pyrrolo[3,4-d]isoxazole-5(4H)-carboxylate | 1253183-39-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: tert-butyl 3-benzyl-6,6a-dihydro-3aH-pyrrolo[3,4-d]isoxazole-5(4H)-carboxylate
• 英文别名: Tert-butyl 3-benzyl-3a,4,6,6a-tetrahydropyrrolo[3,4-d][1,2]oxazole-5-carboxylate
• CAS: 1253183-39-9
• 化学式: C₁₇H₂₂N₂O₃
• 分子量: 302.373
• InChiKey: BKYLWXUXXZHBMV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  51.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl 3-benzyl-6,6a-dihydro-3aH-pyrrolo[3,4-d]isoxazole-5(4H)-carboxylate 在 盐酸 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 丙酮 为溶剂， 反应 13.0h， 生成 3-benzyl-5-methyl-4,5,6,6a-tetrahydro-3aH-pyrrolo[3,4-d]isoxazole
  参考文献：
  名称：

  Synthesis and Biochemical Evaluation of Δ²-Isoxazoline Derivatives as DNA Methyltransferase 1 Inhibitors

  摘要：

  A series of Delta(2)-isoxazoline constrained analogues of procaine/procainamide (7a-k and 8a-k) were prepared and their inhibitory activity against DNA methyltransferase I (DNMT1) was tested. Among them, derivative 7b is far more potent in vitro (IC50 = 150 mu M) than other non-nucleoside inhibitors and also exhibits a strong and dose-dependent antiproliferative effect against HCT116 human colon carcinoma cells. The binding mode of 7b with the enzyme was also investigated by means of a simple competition assay as well as of docking simulations conducted using the recently published crystallographic structure of human DNMT1. On the basis of the findings, we assessed that the mode of inhibition of 7b is consistent with a competition with the cofactor and propose it as a novel lead compound for the development of non-nucleoside DNMT inhibitors.

  DOI：

  10.1021/jm2010404
• 作为产物：
  描述：

  苯乙醛肟 在 吡啶 、 N-氯代丁二酰亚胺 、 potassium carbonate 作用下， 以 氯仿 、 乙酸乙酯 为溶剂， 40.0~90.0 ℃ 、689.49 kPa 条件下， 反应 0.17h， 生成 tert-butyl 3-benzyl-6,6a-dihydro-3aH-pyrrolo[3,4-d]isoxazole-5(4H)-carboxylate
  参考文献：
  名称：

  Synthesis and Biochemical Evaluation of Δ²-Isoxazoline Derivatives as DNA Methyltransferase 1 Inhibitors

  摘要：

  A series of Delta(2)-isoxazoline constrained analogues of procaine/procainamide (7a-k and 8a-k) were prepared and their inhibitory activity against DNA methyltransferase I (DNMT1) was tested. Among them, derivative 7b is far more potent in vitro (IC50 = 150 mu M) than other non-nucleoside inhibitors and also exhibits a strong and dose-dependent antiproliferative effect against HCT116 human colon carcinoma cells. The binding mode of 7b with the enzyme was also investigated by means of a simple competition assay as well as of docking simulations conducted using the recently published crystallographic structure of human DNMT1. On the basis of the findings, we assessed that the mode of inhibition of 7b is consistent with a competition with the cofactor and propose it as a novel lead compound for the development of non-nucleoside DNMT inhibitors.

  DOI：

  10.1021/jm2010404

文献信息

• Synthesis of 3-Aryl/benzyl-4,5,6,6a-tetrahydro-3a<i>H</i>-pyrrolo[3,4-<i>d</i>]isoxazole Derivatives: A Comparison between Conventional, Microwave-Assisted and Flow-Based Methodologies
  作者：Sabrina Castellano、Lucia Tamborini、Monica Viviano、Andrea Pinto、Gianluca Sbardella、Paola Conti

  DOI：10.1021/jo1014323

  日期：2010.11.5

  Two modern synthetic technologies to perform 1,3-dipolar cycloaddition reactions were compared. This study puts in evidence the power of microwave-assisted and flow-based methodologies compared to the conventional one in terms of reaction time and yield, and demonstrates the potential of flow chemistry in terms of time, automation, and scaling up opportunities.

  比较了进行1，3-偶极环加成反应的两种现代合成技术。这项研究证明了微波辅助和基于流的方法在反应时间和收率方面与传统方法相比具有强大的优势，并从时间，自动化和扩大规模方面证明了流化学的潜力。
• Synthesis and Biochemical Evaluation of Δ²-Isoxazoline Derivatives as DNA Methyltransferase 1 Inhibitors
  作者：Sabrina Castellano、Dirk Kuck、Monica Viviano、Jakyung Yoo、Fabian López-Vallejo、Paola Conti、Lucia Tamborini、Andrea Pinto、José L. Medina-Franco、Gianluca Sbardella

  DOI：10.1021/jm2010404

  日期：2011.11.10

  A series of Delta(2)-isoxazoline constrained analogues of procaine/procainamide (7a-k and 8a-k) were prepared and their inhibitory activity against DNA methyltransferase I (DNMT1) was tested. Among them, derivative 7b is far more potent in vitro (IC50 = 150 mu M) than other non-nucleoside inhibitors and also exhibits a strong and dose-dependent antiproliferative effect against HCT116 human colon carcinoma cells. The binding mode of 7b with the enzyme was also investigated by means of a simple competition assay as well as of docking simulations conducted using the recently published crystallographic structure of human DNMT1. On the basis of the findings, we assessed that the mode of inhibition of 7b is consistent with a competition with the cofactor and propose it as a novel lead compound for the development of non-nucleoside DNMT inhibitors.