9-((3aR,4R,6R,6aR)-6-(((tert-butyldimethylsilyl)oxy)methyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)-6-chloro-9H-purine | 139301-94-3

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 9-((3aR,4R,6R,6aR)-6-(((tert-butyldimethylsilyl)oxy)methyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)-6-chloro-9H-purine
• 英文别名: [(3aR,4R,6R,6aR)-4-(6-chloropurin-9-yl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methoxy-tert-butyl-dimethylsilane
• CAS: 139301-94-3
• 化学式: C₁₉H₂₉ClN₄O₄Si
• 分子量: 441.002
• InChiKey: QASPGMKGVYKWRD-LSCFUAHRSA-N

物化性质

• 沸点：
  530.8±60.0 °C(Predicted)
• 密度：
  1.34±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.92
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  80.5
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  9-((3aR,4R,6R,6aR)-6-(((tert-butyldimethylsilyl)oxy)methyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)-6-chloro-9H-purine 在 2,2,6,6-tetramethylpiperidinyl-lithium 、 三丁基氯化锡 、 碘 作用下， 以 四氢呋喃 为溶剂， 反应 2.5h， 生成 9-((3aR,4R,6R,6aR)-6-((tert-butyldimethylsilyloxy)methyl)-2,2-dimethyl-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl)-6-chloro-2-iodo-9H-purine
  参考文献：
  名称：

  SAR around (l)-S-adenosyl-l-homocysteine, an inhibitor of human DNA methyltransferase (DNMT) enzymes

  摘要：

  The inhibitory activity of base-modified SAH analogues and the specificity of inhibiting human DNMT1 and DNMT3b2 enzymes was explored. The 6-amino group was essential while the 7-N of the adenine ring of SAH could be replaced by CH- without loss of activity against both enzymes. The introduction of small groups at the 2-position of the adenine moiety favors DNMT1 over DNMT3b2 inhibition whereas alkylation of the N-6-amino moiety favors the inhibition of DNMT3b2 enzyme. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.03.113
• 作为产物：
  描述：

  2’,3’,5’-三乙酰肌苷 在 咪唑 、 (chloromethylene)dimethyl iminium chloride 、 氨 、 对甲苯磺酸 、 丙酮 作用下， 以 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 35.75h， 生成 9-((3aR,4R,6R,6aR)-6-(((tert-butyldimethylsilyl)oxy)methyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)-6-chloro-9H-purine
  参考文献：
  名称：

  Diimidazo[1,2-c:4′,5′-e]pyrimidines: N6-N1 conformationally restricted adenosines

  摘要：

  Tethering the N-6-substituents of N-6-substituted adenosines to N1 has resulted in a series of conformationally restricted adenosine analogues. The resultant diimidazo[1,2-c:4',5'-e]pyrimidines were shown to be adenosine A(1) selective. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(98)00101-2

文献信息

• Purine derivatives
  申请人：Mantell Simon J.

  公开号：US06900309B1

  公开（公告）日：2005-05-31

  The present invention relates to compounds of the formula and pharmaceutically acceptable salts and solvates thereof, and to processes for the preparation of, intermediates used in the preparation of, compositions containing and the uses of, such compounds as adenosine A2a receptor agonists.

  本发明涉及具有以下公式的化合物、以及它们的药用可接受盐和溶剂化物，还涉及制备这些化合物、在制备中使用的中间体、包含这些化合物的组合物以及作为腺苷A2a受体激动剂的用途。
• Inhibitors of DNA Methyltransferase
  申请人：Wahhab Amal

  公开号：US20080132525A1

  公开（公告）日：2008-06-05

  The invention relates to the inhibition of DNA methyltransferase isoforms DNMT1 and DNMT3b2. The invention provides compounds and methods for inhibiting DNMT1 and DNMT3b2.

  这项发明涉及抑制DNA甲基转移酶亚型DNMT1和DNMT3b2。该发明提供了用于抑制DNMT1和DNMT3b2的化合物和方法。
• Structure-Guided Drug Design of 6-Substituted Adenosine Analogues as Potent Inhibitors of <i>Mycobacterium tuberculosis</i> Adenosine Kinase
  作者：Roberto A. Crespo、Qun Dang、Nian E. Zhou、Liam M. Guthrie、Thomas C. Snavely、Wen Dong、Kimberly A. Loesch、Takao Suzuki、Lanying You、Wei Wang、Theresa O’Malley、Tanya Parish、David B. Olsen、James C. Sacchettini

  DOI：10.1021/acs.jmedchem.9b00020

  日期：2019.5.9

  (MtbAdoK) is an essential enzyme of Mtb and forms part of the purine salvage pathway within mycobacteria. Evidence suggests that the purine salvage pathway might play a crucial role in Mtb survival and persistence during its latent phase of infection. In these studies, we adopted a structural approach to the discovery, structure-guided design, and synthesis of a series of adenosine analogues that displayed

  结核分枝杆菌腺苷激酶 (MtbAdoK) 是 Mtb 的一种必需酶，是分枝杆菌内嘌呤补救途径的一部分。有证据表明，嘌呤补救途径可能在 Mtb 感染潜伏期的存活和持续中发挥关键作用。在这些研究中，我们采用结构方法来发现、结构指导设计和合成一系列腺苷类似物，这些类似物对酶的抑制常数范围为 5 至 120 nM。其中两种化合物对 Mtb 表现出低微摩尔活性，半数最大有效抑制浓度为 1.7 和 4.0 μM。我们的选择性和初步药代动力学研究表明，与人类对应物相比，这些化合物对 MtbAdoK 具有更高程度的特异性，并且分别在啮齿动物中具有良好的耐受性。最后，晶体学研究显示了抑制、效力和选择性的分子基础，并揭示了 MtbAdoK 同二聚体特有的潜在治疗相关空腔的存在。
• Inhibitors of E1 activating enzymes
  申请人：Critchley Stephen

  公开号：US20060189636A1

  公开（公告）日：2006-08-24

  This invention relates to compounds that inhibit E1 activating enzymes, pharmaceutical compositions comprising the compounds, and methods of using the compounds. The compounds are useful for treating disorders, particularly cell proliferation disorders, including cancers, inflammatory and neurodegenerative disorders; and inflammation associated with infection and cachexia.

  本发明涉及抑制E1激活酶的化合物，包括该化合物的制药组合物和使用该化合物的方法。该化合物对于治疗疾病特别是细胞增殖性疾病，包括癌症，炎症和神经退行性疾病；以及与感染和消瘦相关的炎症具有用处。
• Substituted pyrrolo[2,3-d]pyrimidines as inhibitors of E1 activating enzymes
  申请人：Millennium Pharmaceuticals, Inc.

  公开号：US07951810B2

  公开（公告）日：2011-05-31

  This invention relates to compounds of formula (I-A) wherein Ring A and the variables X, Y, R3a, R3b, R3c, R3d, R4, R5, R5′, and m are defined herein. The compounds of formula (I-A) inhibit E1 activating enzymes, pharmaceutical compositions comprising the compounds, and methods of using the compounds. The compounds of the invention are useful for treating disorders, particularly cell proliferation disorders, including cancers, inflammatory and neurodegenerative disorders; and inflammation associated with infection and cachexia.

  本发明涉及式(I-A)化合物，其中环A和变量X、Y、R3a、R3b、R3c、R3d、R4、R5、R5'和m在此定义。式(I-A)化合物抑制E1激活酶，包括该化合物的制药组合物和使用该化合物的方法。本发明的化合物可用于治疗疾病，特别是细胞增殖性疾病，包括癌症、炎症和神经退行性疾病；以及与感染和消瘦相关的炎症。