[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-[3-[2-(6-tert-butyl-1H-benzimidazol-2-yl)ethyl]cyclobutyl]-propan-2-ylazanium;hydroxide

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 5'-脱氧核糖核苷
• 英文名称: [(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-[3-[2-(6-tert-butyl-1H-benzimidazol-2-yl)ethyl]cyclobutyl]-propan-2-ylazanium;hydroxide
• 化学式: C30H44N8O4
• 分子量: 580.7
• InChiKey: HBOIBUGYLDDDFE-LOKZIPLLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  42
• 可旋转键数：
  9
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  152
• 氢给体数：
  5
• 氢受体数：
  10

文献信息

• Methods of Synthesizing Substituted Purine Compounds
  申请人：EPIZYME, INC.

  公开号：US20150011495A1

  公开（公告）日：2015-01-08

  The present invention provides an efficient process for the synthesis of (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol and hydrates thereof and methods for treating disorders in which DOT1-mediated protein methylation plays a part, such as cancer and neurological disorders, by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present invention also provides novel crystalline forms of (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol and hydrates thereof (Form A, Form B, and Form C), characterized by a unique X-ray diffraction pattern and Differential Scanning Calorimetry profile, as well as a unique crystalline structure.

  本发明提供了一种有效的合成过程，用于合成(2R,3R,4S,5R)-2-(6-氨基-9H-嘌呤-9-基)-5-((((1r,3S)-3-(2-(5-(叔丁基)-1H-苯并[d]咪唑-2-基)乙基)环丁基)(异丙基)氨基)甲基)四氢呋喃-3,4-二醇及其水合物，并通过向需要治疗DOT1介导的蛋白质甲基化在内的疾病的受试者投与这些化合物和制药组合物来治疗这些疾病，例如癌症和神经系统疾病。本发明还提供了(2R,3R,4S,5R)-2-(6-氨基-9H-嘌呤-9-基)-5-((((1r,3S)-3-(2-(5-(叔丁基)-1H-苯并[d]咪唑-2-基)乙基)环丁基)(异丙基)氨基)甲基)四氢呋喃-3,4-二醇及其水合物的新型晶体形式(Form A、Form B和Form C)，其具有独特的X射线衍射图案和差示扫描量热分析曲线，以及独特的晶体结构。
• METHODS OF SYNTHESIZING SUBSTITUTED PURINE COMPOUNDS
  申请人：EPIZYME, INC.

  公开号：US20160024134A1

  公开（公告）日：2016-01-28

  The present invention provides an efficient process for the synthesis of (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol and hydrates thereof and methods for treating disorders in which DOT1-mediated protein methylation plays a part, such as cancer and neurological disorders, by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present invention also provides novel crystalline forms of (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol and hydrates thereof (Form A, Form B, and Form C), characterized by a unique X-ray diffraction pattern and Differential Scanning calorimetry profile, as well as a unique crystalline structure.

  本发明提供了一种有效的合成(2R,3R,4S,5R)-2-(6-氨基-9H-嘌呤-9-基)-5-((((1r,3S)-3-(2-(5-(叔丁基)-1H-苯并[d]咪唑-2-基)乙基)环丁基)(异丙基)氨基)甲基)四氢呋喃-3,4-二醇及其水合物的过程，并通过向需要治疗DOT1介导的蛋白质甲基化在其中发挥作用的疾病（如癌症和神经系统疾病）的受试者施用这些化合物和药物组合物的方法。本发明还提供了(2R,3R,4S,5R)-2-(6-氨基-9H-嘌呤-9-基)-5-((((1r,3S)-3-(2-(5-(叔丁基)-1H-苯并[d]咪唑-2-基)乙基)环丁基)(异丙基)氨基)甲基)四氢呋喃-3,4-二醇及其水合物的新晶体形式(Form A, Form B和Form C)，其具有独特的X射线衍射图案和差示扫描量热分析谱，以及独特的晶体结构。
• Methods of synthesizing substituted purine compounds
  申请人：Epizyme, Inc.

  公开号：US10968247B2

  公开（公告）日：2021-04-06

  The present invention provides an efficient process for the synthesis of (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol and hydrates thereof and methods for treating disorders in which DOT1-mediated protein methylation plays a part, such as cancer and neurological disorders, by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present invention also provides novel crystalline forms of (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol and hydrates thereof (Form A, Form B, and Form C), characterized by a unique X-ray diffraction pattern and Differential Scanning Calorimetry profile, as well as a unique crystalline structure.

  本发明提供了一种用于合成(2R,3R,4S,5R)-2-(6-氨基-9H-嘌呤-9-基)-5-((((1r,3S)-3-(2-(5-(叔丁基)-1H-苯并[d]咪唑-2-基)乙基)环丁基)(异丙基)氨基)甲基)四氢呋喃-3、4-二醇及其水合物，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由 DOT1 介导的蛋白质甲基化起作用的疾病（如癌症和神经系统疾病）的方法。本发明还提供了新型结晶形式的(2R,3R,4S,5R)-2-(6-氨基-9H-嘌呤-9-基)-5-((((1r,3S)-3-(2-(5-(叔丁基)-1H-苯并[d]咪唑-2-基)乙基)环丁基)(异丙基)氨基)甲基)四氢呋喃-3、4-二醇及其水合物（形式 A、形式 B 和形式 C），具有独特的 X 射线衍射图样和差示扫描量热曲线，以及独特的晶体结构。
• US8920928B2
  申请人：——

  公开号：US8920928B2

  公开（公告）日：2014-12-30
• US9175032B2
  申请人：——

  公开号：US9175032B2

  公开（公告）日：2015-11-03