1-(2-fluorobenzoyl)-β-carboline | 906067-42-3

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 哈马拉生物碱
• 英文名称: 1-(2-fluorobenzoyl)-β-carboline
• 英文别名: (2-fluorophenyl)(9H-pyrido[3,4-b]indol-1-yl)methanone；Methanone, (2-fluorophenyl)-9H-pyrido[3,4-b]indol-1-yl-；(2-fluorophenyl)-(9H-pyrido[3,4-b]indol-1-yl)methanone
• CAS: 906067-42-3
• 化学式: C₁₈H₁₁FN₂O
• 分子量: 290.297
• InChiKey: NMVIJWWJRYJSFV-UHFFFAOYSA-N

物化性质

• 沸点：
  555.0±40.0 °C(Predicted)
• 密度：
  1.372±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  45.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(2-fluorobenzoyl)-β-carboline 在 吡啶盐酸盐 作用下， 反应 0.67h， 以80%的产率得到海洋活性生物碱
  参考文献：
  名称：

  A new method for the synthesis of the marine alkaloid fascaplysin based on the microwave-assisted Minisci reaction

  摘要：

  A new two-step method for the synthesis of the marine alkaloid fascaplysin has been developed, via homolytic benzoylation (Minisci reaction) of beta-carboline under microwave irradiation followed by intermolecular quaternization. (c) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2013.04.113
• 作为产物：
  描述：

  1-(2-fluorobenzoyl)-3,4-dihydro-β-carboline 在 氧气 作用下， 以 甲苯 为溶剂， 生成 1-(2-fluorobenzoyl)-β-carboline
  参考文献：
  名称：

  Synthesis, crystal structure and biological activity of β-carboline based selective CDK4-cyclin D1 inhibitors

  摘要：

  本文展示了一系列非平面二氢-β-卡巴啉和基于β-卡巴啉的衍生物的设计、合成和生物活性，这些衍生物源自毒性抗癌剂法斯卡普利辛。我们证明这些化合物是CDK4的选择性抑制剂，相较于CDK2，系列中最佳化合物4d的IC50（CDK4-细胞周期蛋白D1）为11 µmol。对部分合成化合物（3b/d和4a–d）进行了晶体学分析，以估计设计抑制剂与模型化合物法斯卡普利辛之间的结构相似性。

  DOI：

  10.1039/b613861f

文献信息

• Synthesis, crystal structure and biological activity of β-carboline based selective CDK4-cyclin D1 inhibitors
  作者：Marcos D. García、A. James Wilson、Daniel P. G. Emmerson、Paul R. Jenkins、Sachin Mahale、Bhabatosh Chaudhuri

  DOI：10.1039/b613861f

  日期：——

  The design, synthesis and biological activity of a series of non-planar dihydro-β-carboline and β-carboline-based derivatives of the toxic anticancer agent fascaplysin is presented. We show these compounds to be selective inhibitors of CDK4 over CDK2 with an IC50 (CDK4-cyclin D1) = 11 µmol for the best compound in the series 4d. The crystallographic analysis of some of the compounds synthesised (3b/d and 4a–d) was carried out, in an effort to estimate the structural similarities between the designed inhibitors and the model compound fascaplysin.

  本文展示了一系列非平面二氢-β-卡巴啉和基于β-卡巴啉的衍生物的设计、合成和生物活性，这些衍生物源自毒性抗癌剂法斯卡普利辛。我们证明这些化合物是CDK4的选择性抑制剂，相较于CDK2，系列中最佳化合物4d的IC50（CDK4-细胞周期蛋白D1）为11 µmol。对部分合成化合物（3b/d和4a–d）进行了晶体学分析，以估计设计抑制剂与模型化合物法斯卡普利辛之间的结构相似性。
• Discovery of a marine-derived bis-indole alkaloid fascaplysin, as a new class of potent P-glycoprotein inducer and establishment of its structure–activity relationship
  作者：Sudhakar Manda、Sadhana Sharma、Abubakar Wani、Prashant Joshi、Vikas Kumar、Santosh K. Guru、Sonali S. Bharate、Shashi Bhushan、Ram A. Vishwakarma、Ajay Kumar、Sandip B. Bharate

  DOI：10.1016/j.ejmech.2015.10.049

  日期：2016.1

  The screening of IIIM natural products repository for P-gp modulatory activity in P-gp over-expressing human adenocarcinoma LS-180 cells led to the identification of 7 natural products viz. withaferin, podophyllotoxin, 3-demethylcolchicine, agnuside, reserpine, seseberecine and fascaplysin as P-gp inducers. Fascaplysin (6a), a marine-derived bis-indole alkaloid, was the most potent among all of them, showing induction of P-gp with EC50 value of 25 nM. P-gp induction is one of the recently targeted strategy to increase amyloid-beta clearance from Alzheimer brains. Thus, we pursued a medicinal chemistry of fascaplysin to establish its structure activity relationship for P-gp induction activity. Four series of analogs viz, substituted quaternary fascaplysin analogs, D-ring opened quaternary analogs, D-ring opened non-quaternary analogs, and beta-carbolinium analogs were synthesized and screened for P-gp induction activity. Among the total of 48 analogs screened, only quaternary nitrogen containing analogs 6a-g and 10a, 10h-1 displayed promising P-gp induction activity; whereas non-planar non-quaternary analogs 9a-m, 13a-n, 15a-h were devoid of this activity. The P-gp induction activity of best compounds was then confirmed by western-blot analysis, which indicated that fascaplysin (6a) along with 4,5-difluoro analog of fascaplysin 6f and D-ring opened analog 10j displayed 4-8 fold increase in P-gp expression in LS-180 cells at 1 mu M. Additionally, compounds 6a and 6f also showed inhibition of acetylcholinestease (AChE), an enzyme responsible for neuronal loss in Alzheimer's disease. Thus, fascaplysin and its analogs showing promising P-gp induction along with AChE inhibition at 1 mu M, with good safety window (LS-180: IC50 > 10 mu M, hGF: 4 mu M), clearly indicates their promise for development as an anti-Alzheimer agent. (C) 2015 Elsevier Masson SAS. All rights reserved.
• Regioselective photo-oxidation of 1-benzyl-4,9-dihydro-3H-β-carbolines
  作者：Marcos D. García、A. James Wilson、Daniel P. G. Emmerson、Paul R. Jenkins

  DOI：10.1039/b604922b

  日期：——

  The synthesis of a series of β-carboline-based analogues of the natural product fascaplysin is presented; the compounds were produced using a novel photo-oxidation reaction of 1-benzyl-4,9-dihydro-3H-β-carbolines as the key step.

  本文展示了一系列基于β-卡波啉的天然产物fascaplysin的类似物的合成；这些化合物是通过1-苄基-4,9-二氢-3H-β-卡波啉的创新光氧化反应作为关键步骤生产的。
• A new method for the synthesis of the marine alkaloid fascaplysin based on the microwave-assisted Minisci reaction
  作者：Maxim E. Zhidkov、Vladimir A. Kaminskii

  DOI：10.1016/j.tetlet.2013.04.113

  日期：2013.7

  A new two-step method for the synthesis of the marine alkaloid fascaplysin has been developed, via homolytic benzoylation (Minisci reaction) of beta-carboline under microwave irradiation followed by intermolecular quaternization. (c) 2013 Elsevier Ltd. All rights reserved.