1-(3,4-dihydro-1H-pyrido[3,4-b]indol-2(9H)-yl)-2-phenylethanone

• 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-(3,4-dihydro-1H-pyrido[3,4-b]indol-2(9H)-yl)-2-phenylethanone
• 英文别名: N-phenylacetyl-1,3,4,9-tetrahydro-1H-β-carboline；N-phenylacetyl-1,3,4,9-tetrahydro-β-carboline；Tgf|A-IN-1；2-phenyl-1-(1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl)ethanone
• 化学式: C₁₉H₁₈N₂O
• 分子量: 290.365
• InChiKey: XSMGRNXXGNCJBN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  36.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1-(3,4-dihydro-1H-pyrido[3,4-b]indol-2(9H)-yl)-2-phenylethanone 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 8-fluoro-N-phenylacetyl-2,3,4,9-tetrahydro-1H-β-carboline
  参考文献：
  名称：

  芳香烷酰基四氢-β-咔啉及其衍生物在治疗代 谢性疾病中的应用

  摘要：

  本发明公开了一种由结构式(I)表示的芳香基烷酰基四氢-β-咔啉类化合物及相关类似物或其水合物或药学上可接受的盐，含有本发明化合物或其药物组合物在制备治疗各种代谢性疾病药物中的用途。

  公开号：

  CN102977091B
• 作为产物：
  描述：

  吲哚 在 lithium aluminium tetrahydride 、 ammonium acetate 、 1-羟基苯并三唑 、 溶剂黄146 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三氯氧磷 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 42.17h， 生成 1-(3,4-dihydro-1H-pyrido[3,4-b]indol-2(9H)-yl)-2-phenylethanone
  参考文献：
  名称：

  发现四氢ß-咔啉衍生物作为新型磷酸二酯酶4抑制剂

  摘要：

  摘要磷酸二酯酶4是负责释放促炎性介质的许多细胞中第二信使cAMP降解的主要酶。抑制这种酶可以帮助控制各种炎症，例如哮喘，慢性阻塞性肺疾病，关节炎和牛皮癣。在这项研究中，通过结合他达拉非和吡拉米司的药效学特征，设计了两个新颖的四氢-β-咔啉系列。合成了22种化合物，并评估了其对磷酸二酯酶4的抑制作用，其中四种显示出比参考化合物IBMX更高的活性。对接研究表明，所制备的化合物与关键的Gln443相互作用，并且与疏水口袋Q2具有可变的相互作用。这是四氢-β-咔啉作为抑制磷酸二酯酶4的支架的首次报道。当前，进行了取代基的进一步优化以微调疏水相互作用并增强该新型抑制剂系列的效力。 图形概要

  DOI：

  10.1007/s00044-017-2011-x

文献信息

• Design, synthesis and biological activity of new CDK4-specific inhibitors, based on fascaplysin
  作者：Carine Aubry、A. James Wilson、Paul R. Jenkins、Sachin Mahale、Bhabatosh Chaudhuri、Jean-Didier Maréchal、Michael J. Sutcliffe

  DOI：10.1039/b518019h

  日期：——

  We present the design, synthesis, and biological activity of three classes of tryptamine derivatives, which are non-planar analogues of the toxic anti-cancer agent fascaplysin. We show these compounds to be selective inhibitors of CDK4 over CDK2, the most active compound 9q has an IC50 for the inhibition of CDK4 of 6 µM.

  我们介绍了三类色胺衍生物的设计、合成及其生物活性，这些衍生物是非平面型的毒性抗癌剂fascaplysin的类似物。我们表明这些化合物是CDK4相对于CDK2的选择性抑制剂，活性最强的化合物9q对CDK4的抑制作用具有6 µM的IC50值。
• Synthesis and Biological Evaluation of Novel Tetrahydro-β-carboline Derivatives as Antitumor Growth and Metastasis Agents through Inhibiting the Transforming Growth Factor-β Signaling Pathway
  作者：Cong Zheng、Yuanzhang Fang、Weiguang Tong、Guoliang Li、Haigang Wu、Wenbo Zhou、Qingxiang Lin、Feifei Yang、Zhengfeng Yang、Peng Wang、Yangrui Peng、Xiufeng Pang、Zhengfang Yi、Jian Luo、Mingyao Liu、Yihua Chen

  DOI：10.1021/jm401117t

  日期：2014.2.13

  The transforming growth factor beta (TGF beta) signaling cascade is considered as one of the pivotal oncogenic pathways in most advanced cancers. Inhibition of the TGF beta signaling pathway by specific antagonists, neutralizing antibodies, or small molecules is considered as an effective strategy for the treatment of tumor growth and metastasis. Here we demonstrated the identification of a series of tetrahydro-beta-carboline derivatives from virtual screening which potentially inhibit the TGF beta signaling pathway. Optimization of the initial hit compound 2-benzoyl-1,3,4,9-tetrahydro-beta-carboline (8a) through substitution at different positions to define the structure-activity relationship resulted in the discovery of potent inhibitors of the TGF beta signaling pathway. Among them, compound 8d, one of the tested compounds, not only showed potent inhibition of lung cancer cell proliferation and migration in vitro but also strongly suppressed growth of lung cancer and breast cancer in vivo.
• METHODS FOR ENHANCING THE EFFICIENCY OF GENE EDITING
  申请人：Dana-Farber Cancer Institute, Inc.

  公开号：EP3433362B1

  公开（公告）日：2021-05-05
• METHODS OF PREDICTING AND PREVENTING CANCER IN PATIENTS HAVING PREMALIGNANT LESIONS
  申请人：INSERM (Institut National de la Santé et de la Recherche Médicale)

  公开号：US20220177978A1

  公开（公告）日：2022-06-09

  As advanced cancer has poor prognosis, its detection and treatment at the earliest stages is critical to increase cancer survival rate. Therefore, elucidating the determinants of the intra-lesion immune reaction during cancer's developments is critical for moving into precision medicine and immunotherapy-based cancer prevention. Adaptive immune response within tumors was shown to be the strongest at the earliest stage of carcinoma. Thus, the inventors hypothesized that the immune microenvironment and adaptive immunity were first established at early stage of lung carcinogenesis. Here they identified changes in the tumor molecular profile and its microenvironment during the successive steps of lung squamous carcinogenesis, using gene expression profiling and multispectral imaging. A unique and invaluable dataset of (9) morphological stages of development was analyzed, including (122) well-annotated biopsies from (77) patients. In particular, the inventors show that immune activation and immune escape occur before tumor invasion, and that immunosuppressive cytokines and checkpoint receptors immune escape mechanisms are concomitant with anti-tumor immunity in high-grade dysplasia. Thus, the present invention relates to methods of predicting and preventing cancer in subjects having premalignant lesions.
• 芳香烷酰基四氢-β-咔啉及其衍生物在治疗代 谢性疾病中的应用
  申请人：华东师范大学

  公开号：CN102977091B

  公开（公告）日：2016-03-09

  本发明公开了一种由结构式(I)表示的芳香基烷酰基四氢-β-咔啉类化合物及相关类似物或其水合物或药学上可接受的盐，含有本发明化合物或其药物组合物在制备治疗各种代谢性疾病药物中的用途。