7-(4-acetylphenyl)-1,10-dihydropyrrolo[2,3-a]carbazole | 1192248-56-8

• 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: 7-(4-acetylphenyl)-1,10-dihydropyrrolo[2,3-a]carbazole
• 英文别名: 1-[4-(1,10-Dihydropyrrolo[2,3-a]carbazol-7-yl)phenyl]ethanone
• CAS: 1192248-56-8
• 化学式: C₂₂H₁₆N₂O
• 分子量: 324.382
• InChiKey: LKHSHKRKEPEPKU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  48.6
• 氢给体数：
  2
• 氢受体数：
  1

反应信息

• 作为产物：
  描述：

  在 水 、 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 12.0h， 以195 mg的产率得到7-(4-acetylphenyl)-1,10-dihydropyrrolo[2,3-a]carbazole
  参考文献：
  名称：

  Synthesis, Kinase Inhibitory Potencies, and in Vitro Antiproliferative Evaluation of New Pim Kinase Inhibitors

  摘要：

  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.

  DOI：

  10.1021/jm901018f

文献信息

• Novel Pyrrolo [2,3-A] Carbazoles and Use Thereof as PIM Kinase Inhibitors
  申请人：Anizon Fabrice

  公开号：US20110263669A1

  公开（公告）日：2011-10-27

  The invention relates to pyrrolo[2,3-a]carbazole derivatives, to a method for preparing the same, and to the use thereof as PIM kinase inhibitors. The invention can particularly be used in the pharmaceutical field.

  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。
• NOUVEAUX PYRROLO Ý2,3-a¨CARBAZOLES ET LEUR UTILISATION COMME INHIBITEURS DES KINASES PIM
  申请人：Centre National de la Recherche Scientifique

  公开号：EP2326649A1

  公开（公告）日：2011-06-01
• NOUVEAUX PYRROLO[2,3-a]CARBAZOLES ET LEUR UTILISATION COMME INHIBITEURS DES KINASES PIM
  申请人：Centre National de la Recherche Scientifique

  公开号：EP2326649B1

  公开（公告）日：2012-03-28
• JP2011526610A
  申请人：——

  公开号：JP2011526610A

  公开（公告）日：2011-10-13
• US8481586B2
  申请人：——

  公开号：US8481586B2

  公开（公告）日：2013-07-09