2-amino-4-(4'-fluorophenyl)-3-cyano-7,7-dimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline | 911855-56-6

• 英文名称: 2-amino-4-(4'-fluorophenyl)-3-cyano-7,7-dimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline
• 英文别名: 2-Amino-4-(4-fluorophenyl)-7,7-dimethyl-5-oxo-1,4,6,8-tetrahydroquinoline-3-carbonitrile
• CAS: 911855-56-6
• 化学式: C₁₈H₁₈FN₃O
• 分子量: 311.359
• InChiKey: KUSGTXCESJYFIM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  23
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  78.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-amino-4-(4'-fluorophenyl)-3-cyano-7,7-dimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline 、 环己酮 在 三氯化铝 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 4.5h， 以90%的产率得到11-Amino-12-(4-fluorophenyl)-3,3-dimethyl-2,4,5,7,8,9,10,12-octahydroquinolino[2,3-b]quinolin-1-one
  参考文献：
  名称：

  New tacrine-dihydropyridine hybrids that inhibit acetylcholinesterase, calcium entry, and exhibit neuroprotection properties

  摘要：

  In this communication, we describe the synthesis and biological evaluation of tacripyrimedones 1-5, a series of new tacrine-1,4-dihydropyridine hybrids bearing the general structure of 11-amino-12-aryl-3,3- dimethyl-3,4,5,7,8,9,10,12-octahydrodibenzo[b,g][1,8]naphthyridine-1(2H)-one. These multifunctional compounds are moderately potent and selective AChEIs, with no activity toward BuChE. Kinetic analysis and molecular modeling studies point out that the new compounds preferentially bind the peripheral anionic site of AChE. In addition, compounds 1-5 show an excellent neuroprotective pro. le, and a moderate blocking effect of L-type voltage-dependent calcium channels due to the mitigation of [Ca2+]elevation elicited by K+ depolarization. Therefore, they represent a new family of molecules with potential therapeutic application for the treatment of Alzheimer's disease. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.07.005
• 作为产物：
  描述：

  对氟苯甲醛 、 5,5-二甲基-1,3-环己二酮 、 丙二腈 在 ammonium acetate 作用下， 以 neat (no solvent) 为溶剂， 反应 0.25h， 以94%的产率得到2-amino-4-(4'-fluorophenyl)-3-cyano-7,7-dimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline
  参考文献：
  名称：

  独特的金属氧化物磁化方法：纳米Fe 3 O 4 @ TDI @ TiO 2作为一种高效，可磁分离和可回收的非均相纳米催化剂†

  摘要：

  通过将Fe 3 O 4和TiO 2纳米粒子共价接枝到2,4-甲苯二异氰酸酯作为廉价且高反应性的连接基，已经制备了高效且可磁回收的纳米催化剂。通过傅立叶变换红外光谱（FT-IR），场发射扫描电子显微镜（FE-SEM），X射线衍射（XRD），热重分析（TGA）和振动样品磁强分析（FT-IR）研究了这种新型纳米催化剂的形态和结构。 VSM）。探讨了催化剂的催化活性以合成四氢苯并[ b]。在70°C无溶剂条件下，]吡喃和六氢喹啉衍生物具有优异的收率和较短的反应时间。采用实验设计以使用中央复合设计（CCD）优化反应条件。可以通过应用外部磁体设备轻松分离催化剂，并循环使用多达6次，而催化活性不会显着降低，这使其对满足工业需求和环境问题具有极大的益处。这是第一项报道了一种独特的方法，该方法通过使用TDI作为连接剂并通过共价接枝两种金属氧化物来形成纳米催化剂，从而使金属氧化物磁化的独特方法。此外，该方法可

  DOI：

  10.1039/c6cy00316h

文献信息

• Nano-zirconia as an excellent nano support for immobilization of sulfonic acid: a new, efficient and highly recyclable heterogeneous solid acid nanocatalyst for multicomponent reactions
  作者：Ali Amoozadeh、Salman Rahmani、Mehrnoosh Bitaraf、Fatemeh Bolghan Abadi、Elham Tabrizian

  DOI：10.1039/c5nj02430g

  日期：——

  Nano-zirconia-supported sulfonic acid as a novel, highly efficient and recyclable heterogeneous nanocatalyst is reported for the synthesis of multicomponent reactions.

  报告了一种新型的、高效的、可回收的纳米催化剂——纳米氧化锆支撑的磺酸，用于合成多组分反应。

• Design, Synthesis, Molecular Docking Studies and Antitubercular Evaluation of Hexahydroquinolin-2-yl Benzamide Derivatives
  作者：N. Raghavendra Babu、G.S.N. Koteswara Rao、Rajasekhar Reddy Alavala、P.S. Lakshmi Soukya

  DOI：10.14233/ajchem.2021.23364

  日期：——

  A new series of hexahydroquinolin-2-yl benzamide derivatives (BZ1-10) were designed and synthesized. The synthesized compounds were characterized by 1H NMR, IR and ESI-MS spectra and also subjected for molecular docking studies with the target DNA gyrase enzyme (PBD ID: 4B6C). The molecular docking results of synthesized derivatives indicated the best docking score of -5.105 and -5.02 for BZ9 and BZ4, respectively. All the synthesized compounds were screened for antitubercular activity against H37RV strain, among all, two compounds exhibited significant activity at 12.5 μg/mL and 25 μg/mL concentrations. Thus, the MIC values are in between range of 12.5 and 6.25 μg/mL concentrations. The teratogenicity assay of synthesized compounds was performed in zebrafish larvae, out of the ten compounds, BZ4, BZ6 and BZ8 compounds were found to safer at 0.5 μM concentration without any abnormalities.

  一系列新的六氢喹啉-2-基苯甲酰胺衍生物（BZ1-10）被设计并合成。合成的化合物通过1H NMR、IR和ESI-MS光谱进行表征，并进行了与靶DNA旋转酶酶（PBD ID: 4B6C）的分子对接研究。合成衍生物的分子对接结果显示，BZ9和BZ4分别具有最佳的对接得分为-5.105和-5.02。所有合成的化合物均对H37RV菌株的抗结核活性进行了筛选，其中有两种化合物在12.5μg/mL和25μg/mL浓度下表现出显著活性。因此，MIC值在12.5和6.25μg/mL浓度范围之间。合成化合物的致畸性试验在斑马鱼幼虫中进行，其中十种化合物中，BZ4、BZ6和BZ8化合物在0.5μM浓度下未发现任何异常，表现为更安全。
• Sulfamic Acid-functionalized Nano-titanium dioxide as a Novel and Highly Efficient Heterogeneous Nanocatalyst for One-pot and Solvent-free Synthesis of Hexahydroquinolines
  作者：Elham Tabrizian、Ali Amoozadeh

  DOI：10.1002/jccs.201600802

  日期：2017.3

  Hexahydroquinolines are synthesized via one‐pot, four‐component condensation of 1,3‐cyclic diketones, aromatic aldehydes, malononitrile, and ammonium acetate in the presence of sulfamic acid‐functionalized nano‐titanium dioxide as a novel type of heterogeneous nanocatalyst. The optimized reaction condition is achieved using response surface method (Box–Behnken design [BBD]). Operational simplicity

  六氢喹啉是在氨基磺酸官能化的新型纳米二氧化钛存在下，通过一锅，四组分缩合的1,3-环二酮，芳族醛，丙二腈和乙酸铵合成的。使用响应面法（Box–Behnken设计[BBD]）可以达到最佳的反应条件。该方法的主要优点是操作简便，成本低，无毒，催化剂的可重复使用性高，后处理简单，产品收率高。而且，纳米催化剂可以通过离心容易地回收，并且可以有效地重复使用至少七次连续运行。
• One-pot synthesis of hexahydroquinolines<i>Via</i>a four-component cyclocondensation under microwave irradiation in solvent free conditions: A green chemistry strategy
  作者：Shujiang Tu、Jinpeng Zhang、Xiaotong Zhu、Yan Zhang、Qian Wang、Jianing Xu、Bo Jiang、Runhong Jia、Junyong Zhang、Feng Shi

  DOI：10.1002/jhet.5570430425

  日期：2006.7

  Four-component cyclocondensation of aromatic aldehydes, malononitrile, dimedone and ammonium acetate proceeds under microwave irradiation in solvent free conditions to give highly functionalized hexahydroquinolines in excellent yields.

  在无溶剂条件下，在微波辐射下进行芳香醛，丙二腈，二甲酮和乙酸铵的四组分环缩合反应，从而以极高的收率得到高度官能化的六氢喹啉。
• <i>N</i>-(3-silyl propyl) diethylene triamine<i>N,N',N''</i>-tri-sulfonic acid immobilized on Fe_3-xTi_xO₄magnetic nanoparticles: A new recyclable heterogeneous nanocatalyst for the synthesis of hexahydroquinolines
  作者：Davood Azarifar、Younes Abbasi、Omolbanin Badalkhani

  DOI：10.1002/aoc.3939

  日期：2018.1

  immobilization of sulfamic acid groups onto the magnetic support. These nanoparticles exhibited high catalytic activity as novel magnetically recyclable acid nanocatalyst in the synthesis of a diverse range of hexahydroquinolines through one‐pot tandem reactions in excellent yields. Also, this nanocatalyst performed satisfactory catalytic maintenance of activity for the synthesis of the reaction products

  在本研究中，首次将N-（3-甲硅烷基丙基）二亚乙基三胺N，N'，N'' -三磺酸（SPDETATSA）接枝到磁性Fe 3-x Ti x O 4上纳米粒子。基于傅立叶变换红外（FT-IR），能量色散X射线光谱（EDX），扫描电子显微镜（SEM），透射电子显微镜（TEM），热重分析（TGA）表征了所得纳米颗粒的结构），以及振动样品磁力计（VSM）分析。结果证实氨基磺酸基团成功地固定在磁性载体上。这些纳米颗粒通过新型的可磁循环酸纳米催化剂，通过一锅串联反应以优异的产率合成了多种六氢喹啉，表现出很高的催化活性。同样，该纳米催化剂在4轮循环后对合成反应产物进行了令人满意的催化活性维持，活性没有明显损失。