6-fluoro-2,3,4,9-tetrahydro-β-carbolin-1-one | 778-73-4

• 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-fluoro-2,3,4,9-tetrahydro-β-carbolin-1-one
• 英文别名: 6-Fluor-2,3,4,9-tetrahydro-β-carbolin-1-on；6-Fluor-1-oxo-1.2.3.4-tetrahydro-norharman；6-fluoro-1H,2H,3H,4H,9H-pyrido[3,4-b]indol-1-one；6-fluoro-2,3,4,9-tetrahydropyrido[3,4-b]indol-1-one
• CAS: 778-73-4
• 化学式: C₁₁H₉FN₂O
• 分子量: 204.204
• InChiKey: IQEUTWXTWBFKSV-UHFFFAOYSA-N

物化性质

• 熔点：
  236-237 °C(Solv: water (7732-18-5); ethanol (64-17-5))
• 沸点：
  531.0±50.0 °C(Predicted)
• 密度：
  1.404±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  44.9
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-fluoro-2,3,4,9-tetrahydro-β-carbolin-1-one 在 lithium aluminium tetrahydride 作用下， 以 1,4-二氧六环 为溶剂， 生成 6-氟-2,3,4,9-四氢-1H-吡啶并[3,4-b]吲哚
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1021/jm401117t
• 作为产物：
  描述：

  吡啶-2,3-二醇 在 Ru-carbon 甲酸 、 草酰氯 、 氢气 、 二甲基亚砜 、 三乙胺 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 为溶剂， 25.0~50.0 ℃ 、300.0 kPa 条件下， 反应 24.83h， 生成 6-fluoro-2,3,4,9-tetrahydro-β-carbolin-1-one
  参考文献：
  名称：

  Herdeis, Claus; Bissinger, Gerhard, Zeitschrift fur Naturforschung, B: Chemical Sciences, 1987, vol. 42, # 6, p. 785 - 790

  摘要：

  DOI：

文献信息

• Synthetic Fluororutaecarpine Inhibits Inflammatory Stimuli and Activates Endothelial Transient Receptor Potential Vanilloid-Type 1
  作者：Chi-Ming Lee、Jiun-An Gu、Tin-Gan Rau、Chi Wang、Chiao-Han Yen、Shih-Hao Huang、Feng-Yen Lin、Chun-Mao Lin、Sheng-Tung Huang

  DOI：10.3390/molecules22040656

  日期：——

  The natural product, rutaecarpine (RUT), is the main effective component of Evodia rutaecarpa which is a widely used traditional Chinese medicine. It has vasodilation, anticoagulation, and anti-inflammatory activities. However, further therapeutic applications are limited by its cytotoxicity. Thus, a derivative of RUT, 10-fluoro-2-methoxyrutaecarpine (F-RUT), was designed and synthesized that showed no cytotoxicity toward RAW264.7 macrophages at 20 μM. In an anti-inflammation experiment, it inhibited the production of nitric oxide (NO) and tumor necrosis factor (TNF)-α in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages; cyclooxygenase (COX)-2 and inducible NO synthase (iNOS) induced by LPS were also downregulated. After 24 h of treatment, F-RUT significantly inhibited cell migration and invasion of ovarian A2780 cells. Furthermore, F-RUT promoted expressions of transient receptor potential vanilloid type 1 (TRPV1) and endothelial (e)NOS in human aortic endothelial cells, and predominantly reduced the inflammation in ovalbumin/alum-challenged mice. These results suggest that the novel synthetic F-RUT exerts activities against inflammation and vasodilation, while displaying less toxicity than its lead compound.

  天然产品芸香卡品（RUT）是一种广泛使用的传统中药--Evodia rutaecarpa 的主要有效成分。它具有扩张血管、抗凝血和抗炎活性。然而，其细胞毒性限制了其进一步的治疗应用。因此，我们设计并合成了 RUT 的衍生物 10-氟-2-甲氧基吡咯他卡品（F-RUT），该衍生物在 20 μM 时对 RAW264.7 巨噬细胞无细胞毒性。在抗炎实验中，它抑制了脂多糖（LPS）刺激的 RAW264.7 巨噬细胞中一氧化氮（NO）和肿瘤坏死因子（TNF）-α 的产生；LPS 诱导的环氧化酶（COX）-2 和诱导型 NO 合酶（iNOS）也被下调。处理 24 小时后，F-RUT 能显著抑制卵巢 A2780 细胞的迁移和侵袭。此外，F-RUT 还能促进人主动脉内皮细胞中瞬时受体电位香草素 1 型（TRPV1）和内皮（e）NOS 的表达，并主要减轻卵清蛋白/明矾挑战小鼠的炎症反应。这些结果表明，新型合成 F-RUT 具有抗炎和舒张血管的活性，同时其毒性低于其先导化合物。
• RUTAECARPINE ANALOGS AND APPLICATIONS THEREOF
  申请人：TAIPEI MEDICAL UNIVERSITY

  公开号：US20190315746A1

  公开（公告）日：2019-10-17

  The present invention provides RUT analogs with various biological activities. In particular, the biological activities comprise anti-inflammatory activity, vasodilator effects, migration/invasion-suppressive activities, ability against damage due to remodeling between the epithelium and endothelium, collagen deposition and cardiac fibrosis suppress. Snail protein inhibitory effect, etc., which may improve cardiac, vasodilation, and lung functions. The RUT analogs disclosed herein also exhibit a lower cytotoxicity comparing to RUT.

  本发明提供了具有各种生物活性的RUT类似物。特别是，这些生物活性包括抗炎活性、扩血管效应、迁移/侵袭抑制活性、对上皮和内皮重塑所致损伤的能力、胶原沉积和心脏纤维化抑制。蜗牛蛋白抑制效应等，这些可能改善心脏、扩血管和肺功能。本文披露的RUT类似物与RUT相比还表现出较低的细胞毒性。
• Beta-carboline compounds and analogues thereof as mitogen-activated protein kinase-activated protein kinase-2 inhibitors
  申请人：Anderson R. David

  公开号：US20050137220A1

  公开（公告）日：2005-06-23

  A method is described for inhibiting mitogen activated protein kinase-activated protein kinase-2 in a subject in need of such inhibition, where the method involves administering to the subject a beta-carboline MK-2 inhibiting compound, or a pharmaceutically acceptable salt thereof.

  本文描述了一种用于抑制需要这种抑制的受试者中的有丝分裂原活化蛋白激酶激活蛋白激酶-2的方法，其中该方法涉及向受试者施用一种β-喀啉MK-2抑制化合物或其药学上可接受的盐。
• Synthesis and cytotoxic activity of novel quinazolino-β-carboline-5-one derivatives
  作者：Bipul Baruah、Kavitha Dasu、Balasubramanian Vaitilingam、Premkumar Mamnoor、Prasanthi Penubaka Venkata、Sriram Rajagopal、Koteswar Rao Yeleswarapu

  DOI：10.1016/j.bmc.2004.03.005

  日期：2004.5

  A novel series of quinazolino-beta-carbolinone derivatives was synthesized and evaluated for their in vitro and in vivo anticancer activity. Many compounds have shown good in vitro activity in the range 1-8 muM concentration. Three of the compounds were further tested in nude mice bearing HT-29 colon cancer xenografts. (C) 2004 Elsevier Ltd. All rights reserved.
• TW2019/43716
  申请人：——

  公开号：——

  公开（公告）日：——