1-[7-(trifluoromethyl)quinolin-3-yl]ethanone | 1396546-96-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 1-[7-(trifluoromethyl)quinolin-3-yl]ethanone
• 英文别名: 3-acetyl-7-trifluoromethylquinoline；1-(7-(Trifluoromethyl)quinolin-3-yl)ethanone
• CAS: 1396546-96-5
• 化学式: C₁₂H₈F₃NO
• 分子量: 239.197
• InChiKey: VJQAIXSHPMWUNK-UHFFFAOYSA-N

物化性质

• 沸点：
  310.9±37.0 °C(Predicted)
• 密度：
  1.315±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  30
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-[7-(trifluoromethyl)quinolin-3-yl]ethanone 在 N-苄基-1,4-二氢吡啶-3-甲酰胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 22.0h， 生成 1-(1-methyl-7-(trifluoromethyl)-1,4-dihydroquinolin-3-yl)ethanone
  参考文献：
  名称：

  Straightforward Access to a New Class of Dual DYRK1A/CLK1 Inhibitors Possessing a Simple Dihydroquinoline Core

  摘要：

  DYRK（双特异性酪氨酸磷酸化调控激酶）蛋白激酶家族与多种神经退行性疾病的发病机制有关。其中，DYRK1A 蛋白激酶被认为与阿尔茨海默病（AD）和唐氏综合征有关，因此已成为极具吸引力的治疗靶点。DYRKs是CMGC（CDK、MAPKK、GSK3和CLK）激酶组的一个子集。在这组激酶中，类似 CDC2 的激酶（CLKs），如 CLK1，与 DYRKs 关系密切，作为治疗 AD 的潜在靶点也引起了人们的极大兴趣。基于之前文献中描述的抑制剂（即 TG003 和 INDY），我们在这项工作中报告了一类新的二氢喹啉类化合物，它们对 hDYRK1A 和 hCLK1 具有纳摩尔范围的抑制活性。此外，有大量证据表明，氧化应激在老年痴呆症中起着重要作用。令人高兴的是，最有效的双激酶抑制剂 1p 具有抗氧化和清除自由基的特性。最后，本文还讨论了这类新型 DYRK1A/CLK1 抑制剂的药物相似性和分子对接研究。

  DOI：

  10.3390/molecules28010036
• 作为产物：
  描述：

  N-(2-formyl-5-(trifluoromethyl)phenyl)-4-methylbenzenesulfonamide 、 3-丁炔-2-酮 在 三苯基膦 、 盐酸 作用下， 以 乙腈 、 水 为溶剂， 反应 19.08h， 以94%的产率得到1-[7-(trifluoromethyl)quinolin-3-yl]ethanone
  参考文献：
  名称：

  One-Pot Phosphine-Catalyzed Syntheses of Quinolines

  摘要：

  In this study we developed an efficient one-pot procedure for the preparation of 3-substituted and 3,4-disubstituted quinolines from stable starting materials (activated acetylenes reacting with o-tosylamidobenzaldehydes and o-tosylamidophenones, respectively) under mild conditions. The reaction appears to operate under a general base catalysis mechanism, instigated by the beta-phosphonium enoate alpha-vinyl anion generated in situ through nucleophilic addition of PPh3 to the activated alkyne. Michael addition of the deprotonated tosylamides to the activated alkynes and subsequent rapid aldol cyclization led to the formation of labile N-tosyldihydroquinoline intermediates. Driven by aromatization, detosylation of the dihydroquinoline intermediates occurred readily in the presence of dilute aqueous HCl to give the final quinoline products.

  DOI：

  10.1021/jo3015825

文献信息

• One-Pot Phosphine-Catalyzed Syntheses of Quinolines
  作者：San Khong、Ohyun Kwon

  DOI：10.1021/jo3015825

  日期：2012.9.21

  In this study we developed an efficient one-pot procedure for the preparation of 3-substituted and 3,4-disubstituted quinolines from stable starting materials (activated acetylenes reacting with o-tosylamidobenzaldehydes and o-tosylamidophenones, respectively) under mild conditions. The reaction appears to operate under a general base catalysis mechanism, instigated by the beta-phosphonium enoate alpha-vinyl anion generated in situ through nucleophilic addition of PPh3 to the activated alkyne. Michael addition of the deprotonated tosylamides to the activated alkynes and subsequent rapid aldol cyclization led to the formation of labile N-tosyldihydroquinoline intermediates. Driven by aromatization, detosylation of the dihydroquinoline intermediates occurred readily in the presence of dilute aqueous HCl to give the final quinoline products.
• Straightforward Access to a New Class of Dual DYRK1A/CLK1 Inhibitors Possessing a Simple Dihydroquinoline Core
  作者：Mihaela-Liliana Ţînţaş、Ludovic Peauger、Florent Alix、Cyril Papamicaël、Thierry Besson、Jana Sopková-de Oliveira Santos、Vincent Gembus、Vincent Levacher

  DOI：10.3390/molecules28010036

  日期：——

  The DYRK (Dual-specificity tyrosine phosphorylation-regulated kinase) family of protein kinases is involved in the pathogenesis of several neurodegenerative diseases. Among them, the DYRK1A protein kinase is thought to be implicated in Alzheimer’s disease (AD) and Down syndrome, and as such, has emerged as an appealing therapeutic target. DYRKs are a subset of the CMGC (CDK, MAPKK, GSK3 and CLK) group of kinases. Within this group of kinases, the CDC2-like kinases (CLKs), such as CLK1, are closely related to DYRKs and have also sparked great interest as potential therapeutic targets for AD. Based on inhibitors previously described in the literature (namely TG003 and INDY), we report in this work a new class of dihydroquinolines exhibiting inhibitory activities in the nanomolar range on hDYRK1A and hCLK1. Moreover, there is overwhelming evidence that oxidative stress plays an important role in AD. Pleasingly, the most potent dual kinase inhibitor 1p exhibited antioxidant and radical scavenging properties. Finally, drug-likeness and molecular docking studies of this new class of DYRK1A/CLK1 inhibitors are also discussed in this article.

  DYRK（双特异性酪氨酸磷酸化调控激酶）蛋白激酶家族与多种神经退行性疾病的发病机制有关。其中，DYRK1A 蛋白激酶被认为与阿尔茨海默病（AD）和唐氏综合征有关，因此已成为极具吸引力的治疗靶点。DYRKs是CMGC（CDK、MAPKK、GSK3和CLK）激酶组的一个子集。在这组激酶中，类似 CDC2 的激酶（CLKs），如 CLK1，与 DYRKs 关系密切，作为治疗 AD 的潜在靶点也引起了人们的极大兴趣。基于之前文献中描述的抑制剂（即 TG003 和 INDY），我们在这项工作中报告了一类新的二氢喹啉类化合物，它们对 hDYRK1A 和 hCLK1 具有纳摩尔范围的抑制活性。此外，有大量证据表明，氧化应激在老年痴呆症中起着重要作用。令人高兴的是，最有效的双激酶抑制剂 1p 具有抗氧化和清除自由基的特性。最后，本文还讨论了这类新型 DYRK1A/CLK1 抑制剂的药物相似性和分子对接研究。