N1-(((3aR,4R,6R,6aR)-6-(4-((2,4-dimethoxybenzyl)amino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)-N'-isopropylpropane-1,3-diamine | 1380316-01-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N1-(((3aR,4R,6R,6aR)-6-(4-((2,4-dimethoxybenzyl)amino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)-N'-isopropylpropane-1,3-diamine
• 英文别名: N1-(((3aR,4R,6R,6aR)-6-(4-((2,4-dimethoxybenzyl)amino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)-N1-isopropylpropane-1,3-diamine；N'-[[(3aR,4R,6R,6aR)-4-[4-[(2,4-dimethoxyphenyl)methylamino]pyrrolo[2,3-d]pyrimidin-7-yl]-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methyl]-N'-propan-2-ylpropane-1,3-diamine
• CAS: 1380316-01-7
• 化学式: C₂₉H₄₂N₆O₅
• 分子量: 554.69
• InChiKey: MSHFKWCGFNYCPY-PAHOUZJPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  40
• 可旋转键数：
  12
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  118
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  N1-(((3aR,4R,6R,6aR)-6-(4-((2,4-dimethoxybenzyl)amino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)-N'-isopropylpropane-1,3-diamine 在 水 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 5.5h， 生成 1-(3-((((2R,3S,4R,5R)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl)(isopropyl)amino)propyl)-3-(4-(tert-butyl)phenyl)urea
  参考文献：
  名称：

  [EN] 7-DEAZAPURINE MODULATORS OF HISTONE METHYLTRANSFERASE, AND METHODS OF USE THEREOF
  [FR] MODULATEURS À BASE DE 7-DÉAZAPURINE DE L'HISTONE MÉTHYLTRANSFÉRASE ET PROCÉDÉS D'UTILISATION DE CEUX-CI

  摘要：

  公开号：

  WO2012075500A3
• 作为产物：
  描述：

  N-(2,4-dimethoxybenzyl)-7-((3aR,4R,6R,6aR)-6-((isopropylamino)methyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine 在 四丁基碘化铵 、 N,N-二异丙基乙胺 、 甲胺 作用下， 以 甲醇 、 丙腈 为溶剂， 反应 49.08h， 生成 N1-(((3aR,4R,6R,6aR)-6-(4-((2,4-dimethoxybenzyl)amino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)-N'-isopropylpropane-1,3-diamine
  参考文献：
  名称：

  [EN] 7-DEAZAPURINE MODULATORS OF HISTONE METHYLTRANSFERASE, AND METHODS OF USE THEREOF
  [FR] MODULATEURS À BASE DE 7-DÉAZAPURINE DE L'HISTONE MÉTHYLTRANSFÉRASE ET PROCÉDÉS D'UTILISATION DE CEUX-CI

  摘要：

  公开号：

  WO2012075500A3

文献信息

• 7-Deazapurine Modulators of Histone Methyltransferase, and Methods of Use Thereof
  申请人：Epizyme, Inc.

  公开号：US20140073597A1

  公开（公告）日：2014-03-13

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

  本发明涉及化合物、含有该化合物的药物组合物、用于作为组蛋白甲基转移酶调节剂的化合物和组合物的用途，以及通过调节组蛋白甲基转移酶活性来治疗受组蛋白甲基转移酶调节影响的疾病的方法。
• 7-deazapurine modulators of histone methyltransferase, and methods of use thereof
  申请人：Epizyme, Inc.

  公开号：US08722877B2

  公开（公告）日：2014-05-13

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

  本发明涉及化合物、含有这些化合物的药物组合物、这些化合物和组合物作为组蛋白甲基转移酶调节剂的用途，以及影响组蛋白甲基转移酶活性调节的疾病的治疗方法。
• 7-DEAZAPURINE MODULATORS OF HISTONE METHYLTRANSFERASE, AND METHODS OF USE THEREOF
  申请人：Epizyme, Inc.

  公开号：US20160251390A1

  公开（公告）日：2016-09-01

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

  本发明涉及化合物、含有该化合物的药物组合物，该化合物和组合物的用途作为组蛋白甲基转移酶的调节剂，以及治疗受组蛋白甲基转移酶活性调节影响的疾病的方法。
• Methods for the detection and treatment of leukemias that are responsive to DOT1L inhibition
  申请人：MEMORIAL SLOAN-KETTERING CANCER CENTER

  公开号：US10407732B2

  公开（公告）日：2019-09-10

  Disclosed are: (i) methods for identifying leukemia patients who (or leukemia cells that) do not exhibit an MLL-translocation, rearrangement or MLL-partial tandem duplication but who are nonetheless susceptible to treatment with DOT1L inhibitors; and (ii) methods for treating leukemia patients who (or inhibiting proliferation or inducing apoptosis of leukemia cells that) do not exhibit an MLL-translocation, rearrangement or MLL-partial tandem duplication with DOT1L inhibitors. The patients identified as susceptible and the patients (or cells) treated exhibit elevated expression of a HOX cluster gene or of a HOX cluster-associated gene. Elevated expression of such genes can be measured, e.g., by quantitating the relevant RNA and comparing it to that of a healthy individual (or cell) or to a predetermined standard or it can be inferred by determining whether the patient or cell possesses a mutation that is associated with elevated HOX cluster gene or HOX cluster associated gene expression and thereby inferring that the relevant expression with be elevated.

  公开了(i) 用于鉴定那些（或白血病细胞）不表现出 MLL-易位、重排或 MLL 部分串联重复，但仍易受 DOT1L 抑制剂治疗的白血病患者的方法；(ii) 用 DOT1L 抑制剂治疗（或抑制不表现出 MLL-转位、重排或 MLL 部分串联重复的）白血病患者（或抑制白血病细胞增殖或诱导其凋亡）的方法。确定为易感的患者和接受治疗的患者（或细胞）表现出 HOX 簇基因或 HOX 簇相关基因的表达升高。此类基因表达的升高可以测量，例如通过量化相关 RNA 并将其与健康个体（或细胞）的 RNA 或预定标准进行比较，或者通过确定患者或细胞是否具有与 HOX 簇基因或 HOX 簇相关基因表达升高有关的突变，从而推断出相关表达升高。
• METHODS FOR THE DETECTION AND TREATMENT OF LEUKEMIAS THAT ARE RESPONSIVE TO DOT1L INHIBITION
  申请人：MEMORIAL SLOAN-KETTERING CANCER CENTER

  公开号：US20160298195A1

  公开（公告）日：2016-10-13

  Disclosed are: (i) methods for identifying leukemia patients who (or leukemia cells that) do not exhibit an MLL-translocation, rearrangement or MLL-partial tandem duplication but who are nonetheless susceptible to treatment with DOT1L inhibitors; and (ii) methods for treating leukemia patients who (or inhibiting proliferation or inducing apoptosis of leukemia cells that) do not exhibit an MLL-translocation, rearrangement or MLL-partial tandem duplication with DOT1L inhibitors. The patients identified as susceptible and the patients (or cells) treated exhibit elevated expression of a HOX cluster gene or of a HOX cluster-associated gene. Elevated expression of such genes can be measured, e.g., by quantitating the relevant RNA and comparing it to that of a healthy individual (or cell) or to a predetermined standard or it can be inferred by determining whether the patient or cell possesses a mutation that is associated with elevated HOX cluster gene or HOX cluster associated gene expression and thereby inferring that the relevant expression with be elevated.