N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1-methyl-6-(2,2,6,6-tetramethyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide | 1396777-68-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并吡啶类
• 英文名称: N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1-methyl-6-(2,2,6,6-tetramethyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide
• 英文别名: N-[(4,6-dimethyl-2-oxo-1H-pyridin-3-yl)methyl]-1-methyl-6-(2,2,6,6-tetramethyl-1,3-dihydropyridin-4-yl)pyrazolo[3,4-b]pyridine-4-carboxamide
• CAS: 1396777-68-6
• 化学式: C₂₅H₃₂N₆O₂
• 分子量: 448.568
• InChiKey: MYAWTCZOHZPHSF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  33
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  101
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  ethyl 6-hydroxy-1H-pyrazolo[3,4-b]pyridine-4-carboxylate 在 四(三苯基膦)钯 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 sodium carbonate 、 potassium carbonate 、 sodium hydroxide 、 三溴氧磷 作用下， 以 1,4-二氧六环 、 乙醇 、 水 、 二甲基亚砜 、 乙腈 为溶剂， 反应 18.0h， 生成 N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1-methyl-6-(2,2,6,6-tetramethyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide
  参考文献：
  名称：

  The Importance of Being Me: Magic Methyls, Methyltransferase Inhibitors, and the Discovery of Tazemetostat

  摘要：

  Posttranslational methylation of histones plays a critical role in gene regulation. Misregulation of histone methylation can lead to oncogenic transformation. Enhancer of Zeste homologue 2 (EZH2) methylates histone 3 at lysine 27 (H3K27) and abnormal methylation of this site is found in many cancers. Tazemetostat, an EHZ2 inhibitor in clinical development, has shown activity in both preclinical models of cancer as well as in patients with lymphoma or INI1-deficient solid tumors. Herein we report the structure activity relationships from identification of an initial hit in a high-throughput screen through selection of tazemetostat for clinical development. The importance of several methyl groups to the potency of the inhibitors is highlighted as well as the importance of balancing pharmacokinetic properties with potency.

  DOI：

  10.1021/acs.jmedchem.5b01501

文献信息

• Substituted 6,5-Fused Bicyclic Heteroaryl Compounds
  申请人：Epizyme, Inc.

  公开号：US20140057891A1

  公开（公告）日：2014-02-27

  The present invention relates to substituted 6,5-fused bicyclic heteroaryl compounds. The present invention also relates to pharmaceutical compositions containing these compounds and methods of treating cancer by administering these compounds and pharmaceutical compositions to subjects in need thereof.

  本发明涉及取代的6,5-融合双环杂芳基化合物。本发明还涉及含有这些化合物的制药组合物以及通过将这些化合物和制药组合物用于需要的受试者治疗癌症的方法。
• Substituted 6,5-fused bicyclic heteroaryl compounds
  申请人：Epizyme, Inc.

  公开号：US10273223B2

  公开（公告）日：2019-04-30

  The present invention relates to substituted 6,5-fused bicyclic heteroaryl compounds. The present invention also relates to pharmaceutical compositions containing these compounds and methods of treating cancer by administering these compounds and pharmaceutical compositions to subjects in need thereof.

  本发明涉及取代的6,5-融合双环杂芳基化合物。本发明还涉及含有这些化合物的药物组合物，以及通过向有需要的受试者施用这些化合物和药物组合物来治疗癌症的方法。
• SUBSTITUTED 6,5-FUSED BICYCLIC HETEROARYL COMPOUNDS
  申请人：Epizyme, Inc.

  公开号：EP2681216B1

  公开（公告）日：2017-09-27
• US8962620B2
  申请人：——

  公开号：US8962620B2

  公开（公告）日：2015-02-24
• US9206157B2
  申请人：——

  公开号：US9206157B2

  公开（公告）日：2015-12-08