(±)-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1-(1-methoxypropan-2-yl)-2-methyl-1H-indole-3-carboxamide | 1450652-98-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (±)-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1-(1-methoxypropan-2-yl)-2-methyl-1H-indole-3-carboxamide
• 英文别名: N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1-(1-methoxypropane-2-yl)-2-methyl-1H-indole-3-carboxamide；N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1-(1-methoxypropan-2-yl)-2-methyl-1H-indole-3-carboxamide；N-[(4,6-dimethyl-2-oxo-1H-pyridin-3-yl)methyl]-1-(1-methoxypropan-2-yl)-2-methylindole-3-carboxamide
• CAS: 1450652-98-8
• 化学式: C₂₂H₂₇N₃O₃
• 分子量: 381.475
• InChiKey: WKFRRFRFXHKQES-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  72.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-甲基吲哚-3-羧酸乙酯 在 lithium hydroxide monohydrate 、 caesium carbonate 、 三乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 potassium iodide 作用下， 以 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 36.5h， 生成 (±)-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1-(1-methoxypropan-2-yl)-2-methyl-1H-indole-3-carboxamide
  参考文献：
  名称：

  Discovery, design, and synthesis of indole-based EZH2 inhibitors

  摘要：

  The discovery and optimization of a series of small molecule EZH2 inhibitors is described. Starting from dimethylpyridone HTS hit (2), a series of indole-based EZH2 inhibitors were identified. Biochemical potency and microsomal stability were optimized during these studies and afforded compound 22. This compound demonstrates nanomolar levels of biochemical potency (IC50 = 0.002 mu M), cellular potency (EC50 = 0.080 mu M), and afforded tumor regression when dosed (200 mpk SC BID) in an EZH2 dependent tumor xenograft model. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.06.056

文献信息

• MODULATORS OF METHYL MODIFYING ENZYMES, COMPOSITIONS AND USES THEREOF
  申请人：CONSTELLATION PHARMACEUTICALS, INC.

  公开号：US20150376190A1

  公开（公告）日：2015-12-31

  Agents having the structural Formula (II) for modulating histone methyl modifying enzymes, compositions and uses thereof for instance as anti-cancer agents are provided herein.

  本文提供了具有结构式（II）的制剂，用于调节组蛋白甲基修饰酶，例如作为抗癌制剂的组合物和用途。
• US9980952B2
  申请人：——

  公开号：US9980952B2

  公开（公告）日：2018-05-29
• Discovery, design, and synthesis of indole-based EZH2 inhibitors
  作者：Victor S. Gehling、Rishi G. Vaswani、Christopher G. Nasveschuk、Martin Duplessis、Priyadarshini Iyer、Srividya Balasubramanian、Feng Zhao、Andrew C. Good、Robert Campbell、Christina Lee、Les A. Dakin、Andrew S. Cook、Alexandre Gagnon、Jean-Christophe Harmange、James E. Audia、Richard T. Cummings、Emmanuel Normant、Patrick Trojer、Brian K. Albrecht

  DOI：10.1016/j.bmcl.2015.06.056

  日期：2015.9

  The discovery and optimization of a series of small molecule EZH2 inhibitors is described. Starting from dimethylpyridone HTS hit (2), a series of indole-based EZH2 inhibitors were identified. Biochemical potency and microsomal stability were optimized during these studies and afforded compound 22. This compound demonstrates nanomolar levels of biochemical potency (IC50 = 0.002 mu M), cellular potency (EC50 = 0.080 mu M), and afforded tumor regression when dosed (200 mpk SC BID) in an EZH2 dependent tumor xenograft model. (C) 2015 Elsevier Ltd. All rights reserved.