9H-fluoren-9-ylmethyl N-[2-[[(3aR,4R,6R,6aR)-4-(6-aminopurin-9-yl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methylamino]ethyl]carbamate | 1362693-32-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: 9H-fluoren-9-ylmethyl N-[2-[[(3aR,4R,6R,6aR)-4-(6-aminopurin-9-yl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methylamino]ethyl]carbamate
• CAS: 1362693-32-0
• 化学式: C₃₀H₃₃N₇O₅
• 分子量: 571.636
• InChiKey: YUGFKLXEIVCVAK-ZYWWQZICSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  42
• 可旋转键数：
  9
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  148
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  9H-fluoren-9-ylmethyl N-[2-[[(3aR,4R,6R,6aR)-4-(6-aminopurin-9-yl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methylamino]ethyl]carbamate 在 三乙酰氧基硼氢化钠 、 二乙胺 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 4.0h， 生成 tert-butyl (S)-5-((((3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)(2-aminoethyl)amino)-2-((tert-butoxycarbonyl)amino)pentanoate
  参考文献：
  名称：

  [EN] MODULATORS OF HISTONE METHYLTRANSFERASE, AND METHODS OF USE THEREOF
  [FR] MODULATEURS D'HISTONE MÉTHYLTRANSFÉRASE ET LEURS PROCÉDÉS D'UTILISATION

  摘要：

  公开号：

  WO2012082436A3
• 作为产物：
  描述：

  2-(((3aR,4R,6R,6aR)-6-(6-氨基-9H-嘌呤-9-基)-2,2-二甲基四氢呋喃并[3,4-d][1,3]二氧代-4-基)甲基)异吲哚啉-1,3-二酮 在 三乙酰氧基硼氢化钠 、 一水合肼 作用下， 以 乙醇 、 1,2-二氯乙烷 为溶剂， 反应 7.0h， 生成 9H-fluoren-9-ylmethyl N-[2-[[(3aR,4R,6R,6aR)-4-(6-aminopurin-9-yl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methylamino]ethyl]carbamate
  参考文献：
  名称：

  [EN] MODULATORS OF HISTONE METHYLTRANSFERASE, AND METHODS OF USE THEREOF
  [FR] MODULATEURS D'HISTONE MÉTHYLTRANSFÉRASE ET LEURS PROCÉDÉS D'UTILISATION

  摘要：

  公开号：

  WO2012082436A3

文献信息

• Inhibitors of human EZH2, and methods of use thereof
  申请人：Kuntz Kevin Wayne

  公开号：US09175331B2

  公开（公告）日：2015-11-03

  The invention relates to inhibition of wild-type and certain mutant forms of human histone methyltransferase EZH2, the catalytic subunit of the PRC2 complex which catalyzes the mono- through tri-methylation of lysine 27 on histone H3 (H3-K27). In one embodiment the inhibition is selective for the mutant form of the EZH2, such that trimethylation of H3-K27, which is associated with certain cancers, is inhibited. The methods can be used to treat cancers including follicular lymphoma and diffuse large B-cell lymphoma (DLBCL). Also provided are methods for identifying small molecule selective inhibitors of the mutant forms of EZH2 and also methods for determining responsiveness to an EZH2 inhibitor in a subject.

  该发明涉及抑制人类组蛋白甲基转移酶EZH2的野生型和某些突变形式，该酶是PRC2复合物的催化亚单位，催化组蛋白H3（H3-K27）上赖氨酸27的单甲基化至三甲基化。在一种实施方式中，抑制是选择性的，针对EZH2的突变形式，从而抑制了与某些癌症相关的H3-K27的三甲基化。这些方法可用于治疗包括滤泡性淋巴瘤和弥漫性大B细胞淋巴瘤（DLBCL）在内的癌症。还提供了识别EZH2突变形式的小分子选择性抑制剂的方法，以及确定受试者对EZH2抑制剂的反应性的方法。
• Modulators of Histone Methyltransferase, and Methods of Use Thereof
  申请人：Epizyme, Inc.

  公开号：US20160068559A1

  公开（公告）日：2016-03-10

  Disclosed are compounds, pharmaceutical compositions containing the compounds, and the uses of the compounds and compositions as modulators of histone methyltransferases, and for treating diseases influenced by modulation of histone methyltransferase activity.

  本发明涉及一种化合物、含有该化合物的药物组合物，以及将该化合物和组合物用作组蛋白甲基转移酶调节剂，以及治疗受组蛋白甲基转移酶活性调节影响的疾病的用途。
• METHOD FOR DETERMINING THE SUITABILITY OF INHIBITORS OF HUMAN EZH2 IN TREATMENT
  申请人：Epizyme, Inc.

  公开号：EP2614369B1

  公开（公告）日：2016-02-03
• Inhibitors of Human EZH2, and Methods of Use Thereof
  申请人：Kuntz Kevin W.

  公开号：US20130040906A1

  公开（公告）日：2013-02-14

  The invention relates to inhibition of wild-type and certain mutant forms of human histone methyltransferase EZH2, the catalytic subunit of the PRC2 complex which catalyzes the mono- through tri-methylation of lysine 27 on histone H3 (H3-K27). In one embodiment the inhibition is selective for the mutant form of the EZH2, such that trimethylation of H3-K27, which is associated with certain cancers, is inhibited. The methods can be used to treat cancers including follicular lymphoma and diffuse large B-cell lymphoma (DLBCL). Also provided are methods for identifying small molecule selective inhibitors of the mutant forms of EZH2 and also methods for determining responsiveness to an EZH2 inhibitor in a subject.
• Inhibitors of Human EZH2 and Methods of Use Thereof
  申请人：Epizyme, Inc.

  公开号：US20130303555A1

  公开（公告）日：2013-11-14

  The invention relates to determining the presence of an EZH2 gene mutation in a sample from a subject and inhibition of wild-type and certain mutant forms of human histone methyltransferase EZH2, the catalytic subunit of the PRC2 complex which catalyzes the mono-through tri-methylation of lysine 27 on histone H3 (H3-K27). In one embodiment the inhibition is selective for the mutant form of the EZH2, such that trimethylation of H3-K27, which is associated with certain cancers, is inhibited. The methods can be used to treat cancers including follicular lymphoma and diffuse large B-cell lymphoma (DLBCL). Also provided are methods for identifying small molecule selective inhibitors of the mutant forms of EZH2 and also methods for determining responsiveness to an EZH2 inhibitor in a subject.