3-benzyl-5-methyl-4,5,6,6a-tetrahydro-3aH-pyrrolo[3,4-d]isoxazole hydrochloride | 1338733-15-5

• 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: 3-benzyl-5-methyl-4,5,6,6a-tetrahydro-3aH-pyrrolo[3,4-d]isoxazole hydrochloride
• 英文别名: 3-Benzyl-5-methyl-3a,4,6,6a-tetrahydropyrrolo[3,4-d][1,2]oxazole;hydrochloride
• CAS: 1338733-15-5
• 化学式: C₁₃H₁₆N₂O*ClH
• 分子量: 252.744
• InChiKey: ZYRIGSBZGHAPSM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.97
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  24.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  苯乙醛肟 在 吡啶 、 盐酸 、 N-氯代丁二酰亚胺 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 氯仿 、 乙酸乙酯 、 丙酮 为溶剂， 20.0~90.0 ℃ 、689.49 kPa 条件下， 反应 13.34h， 生成 3-benzyl-5-methyl-4,5,6,6a-tetrahydro-3aH-pyrrolo[3,4-d]isoxazole hydrochloride
  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 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.