6-(tert-butyldimethylsilyl)pyrido[2,3-a]pyrrolo[3,4-c]carbazole-5,7-(6H,12H)dione | 799822-56-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 6-(tert-butyldimethylsilyl)pyrido[2,3-a]pyrrolo[3,4-c]carbazole-5,7-(6H,12H)dione
• 英文别名: C6H4C2NH(C5H3N)C4O2N(tert-butyldimethylsilyl)；4-[Tert-butyl(dimethyl)silyl]-4,11,14-triazapentacyclo[11.7.0.02,6.07,12.015,20]icosa-1,6,8,10,12,15,17,19-octaene-3,5-dione
• CAS: 799822-56-3
• 化学式: C₂₃H₂₃N₃O₂Si
• 分子量: 401.54
• InChiKey: OGXQSBAUUFOEAZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.47
• 重原子数：
  29
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  66.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-(tert-butyldimethylsilyl)pyrido[2,3-a]pyrrolo[3,4-c]carbazole-5,7-(6H,12H)dione 以 水 为溶剂， 反应 4.0h， 生成
  参考文献：
  名称：

  Octahedral rhodium(III) complexes as kinase inhibitors: Control of the relative stereochemistry with acyclic tridentate ligands

  摘要：

  Octahedral metal complexes are attractive structural templates for the design of enzyme inhibitors as has been demonstrated, for example, with the development of metallo-pyridocarbazoles as protein kinase inhibitors. The octahedral coordination sphere provides untapped structural opportunities but at the same time poses the drawback of dealing with a large number of stereoisomers. In order to address this challenge of controlling the relative metal-centered configuration, the synthesis of rhodium(III) pyridocarbazole complexes with facially coordinating acyclic tridentate ligands was investigated. A strategy for the rapid synthesis of such complexes is reported, the diastereoselectivities of these reactions were investigated, the structure of several complexes were determined by X-ray crystallography, the high kinetic stability of such complexes in thiol-containing solutions was demonstrated in H-1-NMR experiments, and the protein kinase inhibition ability of this class of complexes was confirmed. It can be concluded that the use of multidentate ligands is currently maybe the most practical strategy to avoid a large number of possible stereoisomers in the course of exploiting octahedral coordination spheres as structural templates for the design of bioactive molecules. (C) 2015 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.jinorgbio.2015.01.005
• 作为产物：
  描述：

  methyl [N-(2-trimethylsilylethoxy)methyl]indole-3-glyoxylate 在 lithium tetrafluoroborate 、 air 、 4 A molecular sieve 、 potassium tert-butylate 、 碘 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 24.5h， 生成 6-(tert-butyldimethylsilyl)pyrido[2,3-a]pyrrolo[3,4-c]carbazole-5,7-(6H,12H)dione
  参考文献：
  名称：

  Pyrido[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-diones: Synthesis, Cyclometalation, and Protein Kinase Inhibition

  摘要：

  本研究公开了吡啶并[2,3-a]吡咯并[3,4-c]咔唑-5,7(6H)-二酮的合成路线，并介绍了随后将其转化为环甲基蛋白激酶抑制剂的实例。

  DOI：

  10.1055/s-2005-865331

文献信息

• Iridium Complex with Antiangiogenic Properties
  作者：Alexander Wilbuer、Danielle H. Vlecken、Daan J. Schmitz、Katja Kräling、Klaus Harms、Christoph P. Bagowski、Eric Meggers

  DOI：10.1002/anie.201000682

  日期：——

  Identified as nanomolar and selective inhibitor of receptor protein kinase VEGFR3 (Flt4), the nontoxic and octahedrally coordinated IrIII complex 1 was synthesized by a stereoselective oxidative addition to a square‐planar coordinated IrI precursor. The arrows in the image indicate positions at which the blood vessel formation in a zebrafish model of angiogenesis has been hampered by 1.

  无毒且八面体配位的Ir III复合物1被鉴定为受体蛋白激酶VEGFR3（Flt4）的纳摩尔浓度和选择性抑制剂，是通过将立体选择性氧化加成到方形平面配位的Ir I前体中而合成的。图像中的箭头表示斑马鱼血管生成模型中的血管形成已受1阻碍的位置。
• Rhenium Complexes with Red‐Light‐Induced Anticancer Activity
  作者：Kathrin Wähler、Anja Ludewig、Patrick Szabo、Klaus Harms、Eric Meggers

  DOI：10.1002/ejic.201301474

  日期：2014.2

  Rhenium(I) pyridocarbazole complexes with photoinduced antiproliferative activity are reported. The substitutionally inert complexes induce cell death by singlet oxygen generation upon irradiation with red light (λ ≥ 620 nm), while only weak background cytotoxicity is observed in the dark. Due to their ability to inhibit protein kinases (nanomolar IC50 values against Pim1 at 10 μM ATP), this class

  报道了具有光诱导抗增殖活性的铼 (I) 吡啶并咔唑配合物。替代惰性复合物在用红光 (λ ≥ 620 nm) 照射时通过产生单线态氧诱导细胞死亡，而在黑暗中仅观察到微弱的背景细胞毒性。由于它们能够抑制蛋白激酶（在 10 μM ATP 下对 Pim1 的纳摩尔 IC50 值），这类铼配合物指向单一药物双功能抗增殖治疗的方向，其中光动力疗法与癌症相关的抑制作用相结合。蛋白激酶。
• Pyridocarbazole‐Rhodium(III) Complexes as Protein Kinase Inhibitors
  作者：Sandra Dieckmann、Radostan Riedel、Klaus Harms、Eric Meggers

  DOI：10.1002/ejic.201101175

  日期：2012.2

  sophisticated structural scaffolds for the design of enzyme inhibitors. Whereas previous work from our laboratory was predominantly based on ruthenium(II), this study evaluates the suitability of rhodium in the +3 oxidation state to serve as a structural centre for the design of inert metal-based enzyme inhibitors. Based on our established staurosporine-inspired metallo-pyridocarbazole scaffold, strategies for

  惰性金属配合物是设计酶抑制剂的复杂结构支架。尽管我们实验室以前的工作主要基于钌 (II)，但本研究评估了 +3 氧化态的铑作为设计惰性金属基酶抑制剂的结构中心的适用性。基于我们建立的 staurosporine 启发的金属吡啶并咔唑支架，开发了方便合成铑 (III)-吡啶并咔唑复合物的策略，并将其应用于蛋白激酶抑制剂的合成。通过 X 射线晶体学研究了几种铑配合物的结构。稳定性研究证实了这种铑配合物在生物相关条件下的高动力学惰性，例如存在毫摩尔浓度的硫醇。最后，发现了一种极其有效的皮摩尔铑蛋白激酶 Pim1 抑制剂。因此，可以得出结论，铑 (III) 扩展了设计具有生物活性的惰性金属配合物的工具箱。
• Correlation between the Stereochemistry and Bioactivity in Octahedral Rhodium Prolinato Complexes
  作者：Rajathees Rajaratnam、Elisabeth K. Martin、Markus Dörr、Klaus Harms、Angela Casini、Eric Meggers

  DOI：10.1021/acs.inorgchem.5b01349

  日期：2015.8.17

  octahedral metal complexes constitutes a key challenge that needs to be overcome in order to fully exploit the structural properties of octahedral metal complexes for applications in the fields of catalysis, materials sciences, and life sciences. Herein, we describe the application of a proline-based chiral tridentate ligand to decisively control the coordination mode of an octahedral rhodium(III) complex

  控制八面体金属配合物的相对和绝对构型是一个关键的挑战，必须充分克服八面体金属配合物的结构特性，才能在催化，材料科学和生命科学领域中应用。在这里，我们描述了基于脯氨酸的手性三齿配体的应用，以决定性地控制八面体铑（III）配合物的配位模式。我们证明了合成对映异构体之间的镜像关系和非对映异构体之间的差异。此外，我们证明，使用已建立的吡啶并咔唑药效基团配体作为有机金属配合物的一部分，相对手性环境（如蛋白激酶）在金属上相对和绝对立体化学的重要性。蛋白激酶分析和抑制数据证实，尽管具有相同的构成，但基于脯氨酸的对映纯铑（III）络合物尽管选择性明确，但它们的选择性性质差异很大。此外，已经显示出两种示例性化合物在离体大鼠肝脏模型中诱导不同的毒性作用。
• Rhenium Complexes with Visible-Light-Induced Anticancer Activity
  作者：Anja Kastl、Sandra Dieckmann、Kathrin Wähler、Timo Völker、Lena Kastl、Anna Lena Merkel、Adina Vultur、Batool Shannan、Klaus Harms、Matthias Ocker、Wolfgang J. Parak、Meenhard Herlyn、Eric Meggers

  DOI：10.1002/cmdc.201300060

  日期：2013.6

  Shedding light on the matter: Rhenium(I) indolato complexes with highly potent visible‐light‐triggered antiproliferative activity (complex 1: EC50 light=0.1 μM vs EC50 dark=100 μM) in 2D‐ and 3D‐organized cancer cells are reported and can be traced back to an efficient generation of singlet oxygen, causing rapid morphological changes and an induction of apoptosis.

  阐明问题：铼 (I) indolato 配合物在 2D 和 3D 组织的癌症中具有高效的可见光触发抗增殖活性（配合物1：EC 50光 = 0.1 μ M vs EC 50暗 = 100 μ M）细胞被报道并且可以追溯到单线态氧的有效产生，导致快速的形态变化和细胞凋亡的诱导。