1-benzenesulfonyl-1,10-dihydropyrrolo[2,3-a]carbazole | 1192248-35-3

• 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: 1-benzenesulfonyl-1,10-dihydropyrrolo[2,3-a]carbazole
• 英文别名: 1-(benzenesulfonyl)-10H-pyrrolo[2,3-a]carbazole
• CAS: 1192248-35-3
• 化学式: C₂₀H₁₄N₂O₂S
• 分子量: 346.409
• InChiKey: XNFANRSZNOIMCL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  63.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-benzenesulfonyl-1,10-dihydropyrrolo[2,3-a]carbazole 在 水 、 sodium hydroxide 作用下， 以 甲醇 、 乙醚 为溶剂， 反应 16.0h， 生成 2-(1,10-Dihydropyrrolo[2,3-a]carbazol-3-yl)-2-oxoacetyl chloride
  参考文献：
  名称：

  Novel Pyrrolo [2,3-A] Carbazoles and Use Thereof as PIM Kinase Inhibitors

  摘要：

  这项发明涉及吡咯并[2,3-a]咔唑衍生物，以及制备该衍生物的方法，以及将其用作PIM激酶抑制剂的用途。该发明特别适用于制药领域。

  公开号：

  US20110263669A1
• 作为产物：
  描述：

  1-(Phenylsulfonyl)-7-oxo-4,5,6,7-tetrahydroindole 、 苯肼 在 choline chloride * 2ZnCl2 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 乙酸乙酯 为溶剂， 反应 17.0h， 以78%的产率得到1-benzenesulfonyl-1,10-dihydropyrrolo[2,3-a]carbazole
  参考文献：
  名称：

  Novel Pyrrolo [2,3-A] Carbazoles and Use Thereof as PIM Kinase Inhibitors

  摘要：

  这项发明涉及吡咯并[2,3-a]咔唑衍生物，以及制备该衍生物的方法，以及将其用作PIM激酶抑制剂的用途。该发明特别适用于制药领域。

  公开号：

  US20110263669A1

文献信息

• Synthesis and biological activities of new pyrrolocarbazole-imidazobenzimidazole conjugates
  作者：Fabrice Anizon、Francis Giraud、Ekaterina S. Ivanova、Dmitry N. Kaluzhny、Alexander A. Shtil、Federico Cisnetti、Pascale Moreau

  DOI：10.1016/j.tetlet.2020.152096

  日期：2020.7

  New pyrrolocarbazole-imidazobenzimidazole conjugates were prepared and evaluated for their inhibitory potencies toward Pim-1 kinase, DNA binding and antiproliferative activities against human tumor cell lines. The results demonstrated that conjugation of pyrrolocarbazole Pim inhibitors with imidazobenzimidazole derivatives could enhance the antiproliferative potency of conjugates compared to the derived

  制备了新的吡咯并咔唑-咪唑并苯并咪唑共轭物，并评估了它们对Pim-1激酶的抑制作用，DNA结合和对人肿瘤细胞系的抗增殖活性。结果表明，与衍生化合物相比，吡咯并咔唑Pim抑制剂与咪唑并苯并咪唑衍生物的缀合可以增强缀合物的抗增殖能力。
• Synthesis and activities of new indolopyrrolobenzodiazepine derivatives toward acute myeloid leukemia cells
  作者：Francis Giraud、Marion Bourhis、Edris Ebrahimi、Lars Herfindal、Romy Roy Choudhury、Ronja Bjørnstad、Stein Ove Døskeland、Fabrice Anizon、Pascale Moreau

  DOI：10.1016/j.bmc.2015.10.031

  日期：2015.11

  The synthesis of new indolopyrrolobenzodiazepine derivatives is described. Six compounds were selected for evaluation of cytotoxicity towards acute myeloid leukemia (AML) cells and normal fibroblasts. One compound (29) showed selective AML cell death induction. Its action was only partly overcome by knock-down of p53 or Bcl-2 overexpression, suggesting a strong activation of intrinsic apoptotic pathways. (C) 2015 Elsevier Ltd. All rights reserved.
• Kinase inhibitory potencies and in vitro antiproliferative activities of N-10 substituted pyrrolo[2,3-a]carbazole derivatives
  作者：Rufine Akué-Gédu、Boris Letribot、Emmanuelle Saugues、Eric Debiton、Fabrice Anizon、Pascale Moreau

  DOI：10.1016/j.bmcl.2012.03.098

  日期：2012.6

  Development of potent and selective Pim kinase inhibitors has recently emerged as an important field for the design of new anti-cancer drugs. We report the synthesis of new N-10-substituted pyrrolo[2,3-a] carbazole derivatives and their evaluation as Pim kinase inhibitors. Moreover, in vitro antiproliferative activity of these compounds was evaluated toward a human fibroblast primary culture and three human solid cancer cell lines (PA1, PC3 and DU145). Compounds 3, 7 and 10 showed inhibitory potencies toward Pim-1 and Pim-3 in the nanomolar range. Additionally, dimethylamino analog 10 also demonstrated interesting sub-micromolar antiproliferative activities toward the cell lines tested. (C) 2012 Elsevier Ltd. All rights reserved.
• Use of copper(I) catalyzed azide alkyne cycloaddition (CuAAC) for the preparation of conjugated pyrrolo[2,3-a]carbazole Pim kinase inhibitors
  作者：Boris Letribot、Rufine Akué-Gédu、Niina M. Santio、Malika El-Ghozzi、Daniel Avignant、Federico Cisnetti、Päivi J. Koskinen、Arnaud Gautier、Fabrice Anizon、Pascale Moreau

  DOI：10.1016/j.ejmech.2012.02.009

  日期：2012.4

  We have previously demonstrated that pyrrolo[2,3-a]carbazole-3-carbaldehydes are potent Pim kinase inhibitors with in vitro antiproliferative activities. In the present study, we report the synthesis of new pyrrolocarbazoles substituted at the N-10 position. When their ability to inhibit Pim kinase activities were evaluated in in vitro assays, we observed that this nitrogen atom can be substituted without loss of Pim-1 and Pim-3 inhibitory potencies. Moreover, when we added a fluorescent dansyl group (compound 13), we were able to show that 13 penetrates the plasma membrane and enters the cytoplasm. (C) 2012 Elsevier Masson SAS. All rights reserved.
• Synthesis, Kinase Inhibitory Potencies, and in Vitro Antiproliferative Evaluation of New Pim Kinase Inhibitors
  作者：Rufine Akué-Gédu、Emilie Rossignol、Stéphane Azzaro、Stefan Knapp、Panagis Filippakopoulos、Alex N. Bullock、Jenny Bain、Philip Cohen、Michelle Prudhomme、Fabrice Anizon、Pascale Moreau

  DOI：10.1021/jm901018f

  日期：2009.10.22

  Members of the Pim kinase family have been identified as promising targets for the development of antitumor agents. After a screening of pyrrolo[2,3-a]- and [3,2-a]carbazole derivatives toward 66 protein kinases, we identified pyrrolo[2,3-a]carbazole as a new scaffold to design potent Pim kinase inhibitors. In particular, compound 9 was identified as a low nM selective Pim inhibitor. Additionally, several pyrrolo[2,3-a]carbazole derivatives showed selectivity for Pim-1 and Pim-3 over Pim-2. In vitro antiproliferative activities of 9 and 28, the most potent Pim inhibitors identified, were evaluated toward three human solid cancer cell lines (PA1, PC3, and DU145) and one human fibroblast primary culture, revealing IC50 values in the micromolar range. Finally, the crystal structure of Pim-1 complexed with lead compound 9 was determined. The structure revealed a non-ATP mimetic binding mode with no hydrogen bonds formed with the kinase hinge region and explained the selectivity of pyrrolo[2,3-a]carbazole derivatives for Pim kinases.