9-(4-(4-methylpiperazin-1-yl)butyl)-9H-carbazole | 1092850-70-8

• 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: 9-(4-(4-methylpiperazin-1-yl)butyl)-9H-carbazole
• 英文别名: 9-[4-(4-methylpiperazin-1-yl)butyl]carbazole
• CAS: 1092850-70-8
• 化学式: C₂₁H₂₇N₃
• 分子量: 321.465
• InChiKey: PVKACAYUNAUUFO-UHFFFAOYSA-N

物化性质

• 沸点：
  492.6±45.0 °C(Predicted)
• 密度：
  1.11±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  11.4
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  9-(4-(4-methylpiperazin-1-yl)butyl)-9H-carbazole 在 sodium disulfite 、 zinc(II) chloride 作用下， 以 乙醇 、 水 为溶剂， 反应 24.25h， 生成 3-(5-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-6-(6-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-9-(4-(4-methylpiperazin-1-yl)butyl)-9H-carbazole
  参考文献：
  名称：

  Design and Synthesis of New Benzimidazole–Carbazole Conjugates for the Stabilization of Human Telomeric DNA, Telomerase Inhibition, and Their Selective Action on Cancer Cells

  摘要：

  Cell-permeable small molecules that enhance the stability of the G-quadruplex (G4) DNA structures are currently among the most intensively pursued ligands for inhibition of the telomerase activity. Herein we report the design and syntheses of four novel benzimidazole-carbazole conjugates and demonstrate their high binding affinity to G4 DNA. S1 nuclease assay confirmed the ligand mediated G-quadruplex DNA protection. Additional evidence from Telomeric Repeat Amplification Protocol (TRAP-LIG) assay demonstrated efficient telomerase inhibition activity by the ligands. Two of the ligands showed IC50 values in the sub-micromolar range in the TRAP-LIG assay, which are the best among the benzimidazole derivatives reported so far. The ligands also exhibited cancer cell selective nuclear internalization, nuclear condensation, fragmentation, and eventually antiproliferative activity in long-term cell viability assays. Annexin V-FITC/PI staining assays confirm that the cell death induced by the ligands follows an apoptotic pathway. An insight into the mode of ligand binding was obtained from the molecular dynamics simulations.

  DOI：

  10.1021/jm500427n
• 作为产物：
  描述：

  咔唑 在 strong hydride base 、 mild carbonate base 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 生成 9-(4-(4-methylpiperazin-1-yl)butyl)-9H-carbazole
  参考文献：
  名称：

  [EN] METHOD AND DEVICE FOR RAPID DETECTION OF HEARNPV
  [FR] PROCÉDÉ ET DISPOSITIF DE DÉTECTION RAPIDE DU HEARNPV

  摘要：

  该发明提供了一种用于快速检测HearNPV的特定化合物的方法。该方法包括获取溴化物前体，9-(4-溴丁基)-9H-咔唑，并在预定温度下将溴化物前体构成在乙腈中以获取哌嗪衍生物，9-(4-(4-甲基哌嗪-1-基)丁基)-9H-咔唑。在获取哌嗪衍生物之后，哌嗪被反应以获得中间醛衍生物，9-(4-(4-甲基哌嗪-1-基)丁基)-9H-咔唑-3,6-二醛。进一步回流醛衍生物以获得咔唑衍生物3,6-二(1H-苯并[d]咪唑-2-基)-9-(4-(4-甲基哌嗪-1-基)丁基)-9H-咔唑。此外，该发明提供了一种获取用于快速检测HearNPV的探针的方法。该方法包括选择咔唑衍生物3,6-二(1H-苯并[d]咪唑-2-基)-9-(4-(4-甲基哌嗪-1-基)丁基)-9H-咔唑，将咔唑衍生物构成在有机介质中，并将构成的咔唑衍生物嵌入基底以获得探针。该发明还提供了一种包括探针、检测手段和分析器的设备，用于快速检测HearNPV。

  公开号：

  WO2018225086A1

文献信息

• Synthesis and Biochemical Characterization of New Phenothiazines and Related Drugs as MDR Reversal Agents
  作者：Matthias Schmidt、Marlen Teitge、Marianela E. Castillo、Tobias Brandt、Bodo Dobner、Andreas Langner

  DOI：10.1002/ardp.200800115

  日期：2008.10

  for pharmacophor structures is a promising strategy to increase the efficacy of those drugs still influencing multidrug resistance. In this study a range of phenothiazine derivatives was synthesizied with systematical variation of three molecule domains. The biochemical determination of multidrug resistance reversal activity was achieved with the crystalviolet assay on LLC‐PK1/MDR1 cells. The results

  化疗是治疗癌症最重要的方法之一。然而，化疗期间耐药性的发展是癌症患者治疗失败和生存率下降的主要原因。多药耐药 (MDR) 是 30 多年来广泛研究的耐药形式之一。ATP 结合盒蛋白家族的成员负责以 P-糖蛋白作为最具代表性的转运蛋白的多药耐药性。为了克服多药耐药性，外排泵抑制剂对转运蛋白的药理学调节似乎是首选，但临床前研究并未导致临床应用。因此，对药效基团结构进行系统研究是提高那些仍影响多药耐药性的药物疗效的有前途的策略。在这项研究中，一系列吩噻嗪衍生物合成了三个分子结构域的系统变异。多药耐药逆转活性的生化测定是通过对 LLC-PK1/MDR1 细胞的结晶紫测定实现的。将考虑文献中关于新的结构-活性关系以克服未来耐药性的假设来讨论结果。
• [EN] METHOD AND DEVICE FOR RAPID DETECTION OF HEARNPV<br/>[FR] PROCÉDÉ ET DISPOSITIF DE DÉTECTION RAPIDE DU HEARNPV
  申请人：INDIAN INST SCIENT

  公开号：WO2018225086A1

  公开（公告）日：2018-12-13

  The invention provides a method for obtaining a compound specific for rapid detection of HearNPV. The method includes obtaining a bromide precursor, 9-(4-bromobutyl)-9H-carbazole and constituting the bromide precursor in acetonitrile at a predefined temperature to obtain a piperazine derivative, 9-(4-(4-methylpiperazin-1-yl) butyl)-9H-carbazole. Subsequent to obtaining the piperazine derivative, the piperazine is reacted to obtain an intermediate aldehyde derivative, 9-(4-(4-methylpiperazin-1-yl)butyl)-9H- carbazole-3,6-dicarbaldehyde. The aldehyde derivative is further refluxed to obtain a carbazole derivative 3, 6 -di(1H-benzo [d]imidazol-2-yl)-9-(4-(4- methylpiperazin-1-yl)butyl)-9H-carbazole. Further, the invention provides a method for obtaining a probe for rapid detection for HearNPV. The method includes selecting a carbazole derivative 3, 6 -di(1H-benzo [d]imidazol-2-yl)-9-(4-(4-methylpiperazin-1- yl)butyl)-9H-carbazole, constituting the carbazole derivative in an organic medium and embedding the constituted carbazole derivative onto a substrate to obtain the probe. The invention also provides a device comprising a probe, a detection means and an analyser for rapid detection of HearNPV.

  该发明提供了一种用于快速检测HearNPV的特定化合物的方法。该方法包括获取溴化物前体，9-(4-溴丁基)-9H-咔唑，并在预定温度下将溴化物前体构成在乙腈中以获取哌嗪衍生物，9-(4-(4-甲基哌嗪-1-基)丁基)-9H-咔唑。在获取哌嗪衍生物之后，哌嗪被反应以获得中间醛衍生物，9-(4-(4-甲基哌嗪-1-基)丁基)-9H-咔唑-3,6-二醛。进一步回流醛衍生物以获得咔唑衍生物3,6-二(1H-苯并[d]咪唑-2-基)-9-(4-(4-甲基哌嗪-1-基)丁基)-9H-咔唑。此外，该发明提供了一种获取用于快速检测HearNPV的探针的方法。该方法包括选择咔唑衍生物3,6-二(1H-苯并[d]咪唑-2-基)-9-(4-(4-甲基哌嗪-1-基)丁基)-9H-咔唑，将咔唑衍生物构成在有机介质中，并将构成的咔唑衍生物嵌入基底以获得探针。该发明还提供了一种包括探针、检测手段和分析器的设备，用于快速检测HearNPV。
• SMALL MOLECULE COMPOUNDS FOR STEM CELL DIFFERENTIATION
  申请人：Mercola Mark

  公开号：US20100159596A1

  公开（公告）日：2010-06-24

  Methods and small molecule compounds for stem cell differentiation are provided. One example of a class of compounds that may be used is represented by the compound having the structure IA or IB in the form of free base or a pharmaceutically acceptable salt, hydrate, solvate or N-oxide thereof: R 1 is independently hydrogen or (C 1 -C 6 )alkyl; R 2 is independently hydrogen, (C 1 -C 6 )alkyl, aryl, or heteroaryl; R 2′ is independently hydrogen, (C 1 -C 6 )alkyl, CF 3 or C 2 F 5 ; R 3 is independently (C 1 -C 6 )alkyl, aryl, 2-tetrahydrofurylmethyl, an aliphatic tertiary amine, or 4-methoxybenzyl; or R 2 and R 3 may be joined together to form a 5 or 6 member ring lactone; R 4 is independently hydrogen, (C 1 -C 6 )alkyl, a 2- or 4-R 5 -substituted aromatic ring selected from a 4-R 5 -phenyl or a 2-R 5 -5-pyridyl, aryl, heteroaryl, aliphatic tertiary amine or halogen; and R 5 , R 5′ , R 6 , R 6′ , R 7 , R 7′ , are each independently hydrogen, (C 1 -C 6 )alkyl, aryl, optionally substituted phenyl, heteroaryl, a heterocyclic ring, an aliphatic tertiary amine, or halogen.

  提供干细胞分化的方法和小分子化合物。可以使用的一类化合物的一个示例由结构IA或IB表示，以自由碱基或其药学上可接受的盐，水合物，溶剂或N-氧化物的形式存在：R1独立地是氢或（C1-C6）烷基; R2独立地是氢，（C1-C6）烷基，芳基或杂环芳基; R2'独立地是氢，（C1-C6）烷基，CF3或C2F5; R3独立地是（C1-C6）烷基，芳基，2-四氢呋喃甲基，脂肪族三级胺或4-甲氧基苄基; 或者R2和R3可以结合形成5或6元环内酯; R4独立地是氢，（C1-C6）烷基，2-或4-R5-取代的芳环，选自4-R5-苯基或2-R5-5-吡啶基，芳基，杂环芳基，脂肪族三级胺或卤素; R5，R5'，R6，R6'，R7，R7'独立地是氢，（C1-C6）烷基，芳基，可选取代的苯基，杂环芳基，杂环环，脂肪族三级胺或卤素。
• US9012217B2
  申请人：——

  公开号：US9012217B2

  公开（公告）日：2015-04-21
• Design and Synthesis of New Benzimidazole–Carbazole Conjugates for the Stabilization of Human Telomeric DNA, Telomerase Inhibition, and Their Selective Action on Cancer Cells
  作者：Basudeb Maji、Krishan Kumar、Mangesh Kaulage、K. Muniyappa、Santanu Bhattacharya

  DOI：10.1021/jm500427n

  日期：2014.8.28

  Cell-permeable small molecules that enhance the stability of the G-quadruplex (G4) DNA structures are currently among the most intensively pursued ligands for inhibition of the telomerase activity. Herein we report the design and syntheses of four novel benzimidazole-carbazole conjugates and demonstrate their high binding affinity to G4 DNA. S1 nuclease assay confirmed the ligand mediated G-quadruplex DNA protection. Additional evidence from Telomeric Repeat Amplification Protocol (TRAP-LIG) assay demonstrated efficient telomerase inhibition activity by the ligands. Two of the ligands showed IC50 values in the sub-micromolar range in the TRAP-LIG assay, which are the best among the benzimidazole derivatives reported so far. The ligands also exhibited cancer cell selective nuclear internalization, nuclear condensation, fragmentation, and eventually antiproliferative activity in long-term cell viability assays. Annexin V-FITC/PI staining assays confirm that the cell death induced by the ligands follows an apoptotic pathway. An insight into the mode of ligand binding was obtained from the molecular dynamics simulations.