N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-6-[2-(4-methyl-1-piperazinyl)-4-pyridinyl]-1H-indazole-4-carboxamide | 1404094-16-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-6-[2-(4-methyl-1-piperazinyl)-4-pyridinyl]-1H-indazole-4-carboxamide
• 英文别名: N-[(4,6-dimethyl-2-oxo-1H-pyridin-3-yl)methyl]-6-[2-(4-methylpiperazin-1-yl)pyridin-4-yl]-1-propan-2-ylindazole-4-carboxamide
• CAS: 1404094-16-1
• 化学式: C₂₉H₃₅N₇O₂
• 分子量: 513.643
• InChiKey: YRODTWDCXBRTDY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  38
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  95.4
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  6-溴-4-吲唑甲酸甲酯 在 N-甲基吗啉 、 N-羟基-7-氮杂苯并三氮唑 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 sodium hydride 、 碳酸氢钠 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.58h， 生成 N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-6-[2-(4-methyl-1-piperazinyl)-4-pyridinyl]-1H-indazole-4-carboxamide
  参考文献：
  名称：

  Identification of Potent, Selective, Cell-Active Inhibitors of the Histone Lysine Methyltransferase EZH2

  摘要：

  The histone H3-lysine 27 (H3K27) methyltransferase EZH2 plays a critical role in regulating gene expression, and its aberrant activity is linked to the onset and progression of cancer. As part of a drug discovery program targeting EZH2, we have identified highly potent, selective, SAM-competitive, and cell-active EZH2 inhibitors, including GSK926 (3) and GSK343 (6). These compounds are small molecule chemical tools that would be useful to further explore the biology of EZH2.

  DOI：

  10.1021/ml3003346

文献信息

• Identification of Potent, Selective, Cell-Active Inhibitors of the Histone Lysine Methyltransferase EZH2
  作者：Sharad K. Verma、Xinrong Tian、Louis V. LaFrance、Céline Duquenne、Dominic P. Suarez、Kenneth A. Newlander、Stuart P. Romeril、Joelle L. Burgess、Seth W. Grant、James A. Brackley、Alan P. Graves、Daryl A. Scherzer、Art Shu、Christine Thompson、Heidi M. Ott、Glenn S. Van Aller、Carl A. Machutta、Elsie Diaz、Yong Jiang、Neil W. Johnson、Steven D. Knight、Ryan G. Kruger、Michael T. McCabe、Dashyant Dhanak、Peter J. Tummino、Caretha L. Creasy、William H. Miller

  DOI：10.1021/ml3003346

  日期：2012.12.13

  The histone H3-lysine 27 (H3K27) methyltransferase EZH2 plays a critical role in regulating gene expression, and its aberrant activity is linked to the onset and progression of cancer. As part of a drug discovery program targeting EZH2, we have identified highly potent, selective, SAM-competitive, and cell-active EZH2 inhibitors, including GSK926 (3) and GSK343 (6). These compounds are small molecule chemical tools that would be useful to further explore the biology of EZH2.