(R)-1-(1-(1-(ethylsulfonyl)piperidin-4-yl)ethyl)-2-methyl-N-((6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl)-1H-indole-3-carboxamide

• 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: (R)-1-(1-(1-(ethylsulfonyl)piperidin-4-yl)ethyl)-2-methyl-N-((6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl)-1H-indole-3-carboxamide
• 英文别名: 1-[(1R)-1-(1-ethylsulfonylpiperidin-4-yl)ethyl]-2-methyl-N-[(6-methyl-2-oxo-4-propyl-1H-pyridin-3-yl)methyl]indole-3-carboxamide
• 化学式: C₂₉H₄₀N₄O₄S
• 分子量: 540.727
• InChiKey: WAGAGEBMDGMBPC-HXUWFJFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  38
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  109
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-(2-溴苯基)-3-氧代丁酸甲酯 在 盐酸 、 (1-cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylaminomorpholinocarbenium hexafluorophosphate 、 sodium methylate 、 溶剂黄146 、 N,N-二异丙基乙胺 、 sodium hydroxide 、 2-二环己基磷-2',6'-二异丙氧基-1,1'-联苯 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 (R)-1-(1-(1-(ethylsulfonyl)piperidin-4-yl)ethyl)-2-methyl-N-((6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)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

• INDOLE DERIVATIVES AS MODULATORS OF METHYL MODIFYING ENZYMES, COMPOSITIONS AND USES THEREOF
  申请人：Constellation Pharmaceuticals, Inc.

  公开号：US20160185757A1

  公开（公告）日：2016-06-30

  Agents of formulas (I)/(II)/(III) for modulating methyl modifying enzymes, compositions and uses thereof are provided herein.

  本文提供了用于调节甲基修饰酶的配方代理（I）/（II）/（III），以及其组成物和用途。
• US9969716B2
  申请人：——

  公开号：US9969716B2

  公开（公告）日：2018-05-15
• [EN] INDOLE DERIVATIVES AS MODULATORS OF METHYL MODIFYING ENZYMES, COMPOSITIONS AND USES THEREOF<br/>[FR] DÉRIVÉS D'INDOLE UTILISÉS EN TANT QUE MODULATEURS D'ENZYMES DE MODIFICATION DU MÉTHYLE, COMPOSITIONS ET UTILISATIONS ASSOCIÉES
  申请人：CONSTELLATION PHARMACEUTICALS INC

  公开号：WO2015023915A1

  公开（公告）日：2015-02-19

  Agents of formulas (l)/(ll)/(lll) for modulating methyl modifying enzymes, compositions and uses thereof are provided herein.
• 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.