(R)-DRF053 | 1056016-06-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: (R)-DRF053
• 英文别名: DRF 053；(R)-2-((9-Isopropyl-6-((3-(pyridin-2-yl)phenyl)amino)-9H-purin-2-yl)amino)butan-1-ol；(2R)-2-[[9-propan-2-yl-6-(3-pyridin-2-ylanilino)purin-2-yl]amino]butan-1-ol
• CAS: 1056016-06-8
• 化学式: C₂₃H₂₇N₇O
• 分子量: 417.514
• InChiKey: LWANFAFTTOKZAX-QGZVFWFLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  101
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-(3-硝基苯基)吡啶 在 三正丁胺 、 palladium on activated charcoal 、 氢气 、 三乙胺 作用下， 以 甲醇 、 二甲基亚砜 、 正丁醇 为溶剂， 反应 8.0h， 生成 (R)-DRF053
  参考文献：
  名称：

  通过 Ru3(CO)12 催化的邻位金属化策略对芳烃进行间位选择性 CAr-H 硝化

  摘要：

  描述了过渡金属催化芳烃间位选择性 CAr-H 硝化的第一个例子。以Ru3(CO)12为催化剂，以Cu(NO3)2·3H2O为硝基源，以间位选择性专门硝化了具有多种N-杂环或肟基作为导向基团的广谱芳烃。机理研究表明，形成了一种新的 18e-八面体钌物质作为关键的邻位 CAr-H 金属化中间体，这可能是随后的间选择性亲电芳香取代 (SEAr) 的原因。此外，这种方法为许多有用的药物分子的原子/分步经济合成提供了快速通道策略。

  DOI：

  10.1021/jacs.6b03402

文献信息

• Roscovitine-Derived, Dual-Specificity Inhibitors of Cyclin-Dependent Kinases and Casein Kinases 1
  作者：Nassima Oumata、Karima Bettayeb、Yoan Ferandin、Luc Demange、Angela Lopez-Giral、Marie-Lorène Goddard、Vassilios Myrianthopoulos、Emmanuel Mikros、Marc Flajolet、Paul Greengard、Laurent Meijer、Hervé Galons

  DOI：10.1021/jm800109e

  日期：2008.9.11

  Cyclin-dependent kinases (CDKs) and casein kinases 1 (CK 1) are involved in the two key molecular features of Alzheimer's disease, production of amyloid-beta peptides (extracellular plaques) and hyper-phosphorylation of Tau (intracellular neurofibrillary tangles). A series of 2,6,9-trisubstituted purines, structurally related to the CDK inhibitor roscovitine, have been synthesized. They mainly differ by the substituent on the C-6 position. These compounds were screened for kinase inhibitory activities and antiproliferative effects. Several biaryl derivatives displayed potent inhibition of both CDKs and CK1. In particular, derivative 13a was a potent inhibitor of CDK1/cyclin B (IC50: 220 nM), CDK5/p25 (IC50: 80 nM), and CK1 (IC50: 14 nM). Modeling of these molecules into the ATP-binding pocket of CK1 delta provided a rationale for the increased selectivity toward this kinase. 13a was able to prevent the CK1-dependent production of anyloid-beta in a cell model. CDK/CK1 dual-specificity inhibitors may have important applications in Alzheimer's disease and cancers.
• Targeting Casein Kinase-1 and PI3K/AKT/mTOR Pathways for Treatment of c-Myc-Overexpressing Cancers, Organ Transplant Associated Complications and Autoimmune Diseases
  申请人：The Trustees of Columbia University in the City of New York

  公开号：US20190070183A1

  公开（公告）日：2019-03-07

  The invention relates to the co-administration of select proteasome and PI3K inhibitors is useful for treating c-Myc-overexpressing cancers, particularly hematological cancers such as aggressive B- and T-cell lymphomas. In exemplified embodiments, coadministration of a dual PI3K/CK-1 inhibitor with a proteasome inhibitor synergistically increases cell death of aggressive B- and T-cell lymphomas as well as multiple myeloma over the individual or additive effect of either or both agents. This synergistic effect is associated with the previously unknown inhibition of the kinase casein kinase 1 epsilon (CK-1ε) by a PI3K inhibitor, such as TGR-1202. Accordingly, use of PI3K inhibitors that possess CK-1ε inhibition in combination with proteasome inhibitors provides a new therapy regime for treating c-Myc-overexpressing cancers, and particularly hematological cancers.
• Compounds For Reducing c-Myc In c-Myc Overexpressing Cancers Background
  申请人：The Trustees of Columbia University in the City of New York

  公开号：US20190194212A1

  公开（公告）日：2019-06-27

  The invention relates to new compounds that reduce c-Myc expression and useful for cancer treatment, particularly hematological cancers such as aggressive B- and T-cell lymphomas. The new compounds may be combined with adjunct c-Myc inhibor agents such as a PI3K inhibitor, CK-1 inhibitor, Akt-inhibitor, proteasome inhibitor and/or mTor inhibitor. The c-Myc reducing agent may be provided as a lead-in treatment to reduce or initiate reduction of c-Myc prior to adminstration of the adjunct cancer therapeutic agent. Treatment with a c-Myc reducing agent modulates the disease state of the c-Myc overexpressing cancer making it less malignant and more susceptible to adjunctive cancer therapies.
• Meta-Selective C_Ar–H Nitration of Arenes through a Ru₃(CO)₁₂-Catalyzed Ortho-Metalation Strategy
  作者：Zhoulong Fan、Jiabin Ni、Ao Zhang

  DOI：10.1021/jacs.6b03402

  日期：2016.7.13

  as the catalyst and Cu(NO3)2·3H2O as the nitro source, a wide spectrum of arenes bearing diversified N-heterocycles or oximido as the directing groups were nitrated with meta-selectivity exclusively. Mechanism studies have demonstrated the formation of a new 18e-octahedral ruthenium species as a key ortho-CAr-H metalated intermediate, which may be responsible for the subsequent meta-selective electrophilic

  描述了过渡金属催化芳烃间位选择性 CAr-H 硝化的第一个例子。以Ru3(CO)12为催化剂，以Cu(NO3)2·3H2O为硝基源，以间位选择性专门硝化了具有多种N-杂环或肟基作为导向基团的广谱芳烃。机理研究表明，形成了一种新的 18e-八面体钌物质作为关键的邻位 CAr-H 金属化中间体，这可能是随后的间选择性亲电芳香取代 (SEAr) 的原因。此外，这种方法为许多有用的药物分子的原子/分步经济合成提供了快速通道策略。