1-benzyl-1,2,3,4-tetrahydro-6-methoxyquinoline | 73126-26-8

• 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-benzyl-1,2,3,4-tetrahydro-6-methoxyquinoline
• 英文别名: 1-benzyl-6-methoxy-1,2,3,4-tetrahydroquinoline；6-methoxy-1-benzyl-1,2,3,4-tetrahydroquinoline；1-benzyl-6-methoxy-1,2,3,4-tetrahydro-quinoline；1-Benzyl-6-methoxy-1,2,3,4-tetrahydrochinolin；1-benzyl-6-methoxy-3,4-dihydro-2H-quinoline
• CAS: 73126-26-8
• 化学式: C₁₇H₁₉NO
• 分子量: 253.344
• InChiKey: GDRRJSJSUFSRLX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  12.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-benzyl-1,2,3,4-tetrahydro-6-methoxyquinoline 在 三溴化硼 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 0.5h， 生成 (1-benzyl-3,4-dihydro-2H-quinolin-6-yl) N-(2-methylphenyl)carbamate
  参考文献：
  名称：

  Lead optimization studies towards the discovery of novel carbamates as potent AChE inhibitors for the potential treatment of Alzheimer’s disease

  摘要：

  The optimization of our previous lead compound 1 (AChE IC50 = 3.31 mu M) through synthesis and pharmacology of a series of novel carbamates is reported. The synthesized compounds were evaluated against mouse brain AChE enzyme using the colorimetric method described by Ellman et al. The three compounds 6a (IC50 = 2.57 mu M), 6b (IC50 = 0.70 mu M) and 6i (IC50 = 2.56 mu M) exhibited potent in vitro AChE inhibitory activities comparable to the drug rivastigmine (IC50= 1.11 mu M). Among them, the compound 6b has been selected as possible optimized lead for further neuropharmacological studies. In addition, the AChE-carbamate Michaelis complexes of these potent compounds including rivastigmine and ganstigmine have been modeled using covalent docking protocol of GOLD and important direct/indirect interactions contributing to stabilization of the AChE-carbamate Michaelis complexes have been investigated. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.09.005
• 作为产物：
  描述：

  6-甲氧基喹啉 在 nickel-aluminum alloy 、 potassium carbonate 、 potassium iodide 、 sodium hydroxide 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 1-benzyl-1,2,3,4-tetrahydro-6-methoxyquinoline
  参考文献：
  名称：

  Lead optimization studies towards the discovery of novel carbamates as potent AChE inhibitors for the potential treatment of Alzheimer’s disease

  摘要：

  The optimization of our previous lead compound 1 (AChE IC50 = 3.31 mu M) through synthesis and pharmacology of a series of novel carbamates is reported. The synthesized compounds were evaluated against mouse brain AChE enzyme using the colorimetric method described by Ellman et al. The three compounds 6a (IC50 = 2.57 mu M), 6b (IC50 = 0.70 mu M) and 6i (IC50 = 2.56 mu M) exhibited potent in vitro AChE inhibitory activities comparable to the drug rivastigmine (IC50= 1.11 mu M). Among them, the compound 6b has been selected as possible optimized lead for further neuropharmacological studies. In addition, the AChE-carbamate Michaelis complexes of these potent compounds including rivastigmine and ganstigmine have been modeled using covalent docking protocol of GOLD and important direct/indirect interactions contributing to stabilization of the AChE-carbamate Michaelis complexes have been investigated. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.09.005

文献信息

• Nucleophilic Amination of Methoxy Arenes Promoted by a Sodium Hydride/Iodide Composite
  作者：Atsushi Kaga、Hirohito Hayashi、Hiroyuki Hakamata、Miku Oi、Masanobu Uchiyama、Ryo Takita、Shunsuke Chiba

  DOI：10.1002/anie.201705916

  日期：2017.9.18

  Come full circle: A method for the nucleophilic amination of methoxy arenes was established by using sodium hydride (NaH) in the presence of lithium iodide (LiI). This method offers an efficient route to benzannulated nitrogen heterocycles. Mechanistic studies showed that the reaction proceeds through an unusual concerted nucleophilic aromatic substitution.

  围成一圈：在碘化锂（LiI）存在下，使用氢化钠（NaH）建立了甲氧基芳烃的亲核胺化方法。该方法提供了一条有效的途径来制得二环氮杂环。机理研究表明，该反应通过异常的协同的亲核芳族取代进行。
• Novel Carbamates as Orally Active Acetylcholinesterase Inhibitors Found to Improve Scopolamine-Induced Cognition Impairment: Pharmacophore-Based Virtual Screening, Synthesis, and Pharmacology
  作者：Shailendra S. Chaudhaery、Kuldeep K. Roy、Neeraj Shakya、Gunjan Saxena、Shreesh Raj Sammi、Aamir Nazir、Chandishwar Nath、Anil K. Saxena

  DOI：10.1021/jm100573q

  日期：2010.9.9

  library led to the identification of novel carbamates as potent AChE inhibitors. The synthesis and pharmacological evaluation of nine carbamates against three diverse assay systems, namely (i) in vitro Ellman method, (ii) in vivo passive avoidance test, and (iii) aldicarb-sensitivity assay, led to the discovery of orally active novel AChE inhibitors which improved scopolamine-induce cognition impairment

  据报道，系统的虚拟筛选（VS）实验包括3D药效团的开发，虚拟文库的筛选，合成和药理学。使用HypoGen在一组24种氨基甲酸酯作为AChE抑制剂的训练集上开发了具有一个H键供体和三个疏水特征的预测药效团模型（相关性= 0.955）。该模型在40个氨基甲酸酯的测试集中进行了验证（相关系数= 0.844）。虚拟库基于药效团的VS导致鉴定出新型氨基甲酸酯作为有效的AChE抑制剂。九种氨基甲酸酯的合成和药理学评估，针对三种不同的测定系统，即（i）体外Ellman方法，（ii）体内被动回避测试和（iii）涕灭威敏感性测定，导致发现了口服活性新型AChE抑制剂，该抑制剂可改善东pol碱诱导的瑞士雄性小鼠认知障碍。最后，两种新颖的先导化合物选择85和86作为候选分子用于进一步优化。
• Substituted 1,2,3,4-tetrahydroquinolin-6-yloxypropanes as β3-adrenergic receptor agonists: Design, synthesis, biological evaluation and pharmacophore modeling
  作者：Neeraj Shakya、Kuldeep K. Roy、Anil K. Saxena

  DOI：10.1016/j.bmc.2008.11.030

  日期：2009.1

  four candidates have been identified as possible leads for further development of β3-adrenergic receptor agonists for obesity and Type-II diabetes pharmacotherapy. The free OH and NH functions are found to be essential for β3-adrenergic receptor agonistic activity. Among the synthesized β3-adrenergic receptor agonists having 1,2,3,4-tetrahydroquinoline scaffold, the N-benzyl group is found to be superior

  在搜索强效的β 3 -肾上腺素能受体激动剂，一系列新的取代的-1,2,3,4-四氢喹啉-6- yloxypropanes已经合成并评价它们的β 3 -肾上腺素能受体激动活性（范围从-17.73％至使用成熟的人SK-N-MC神经母细胞瘤细胞模型在10μM时抑制90.64％。四个分子即。11，15，22和23表明β 3 -AR激动剂IC 50 0.55，0.59，1.18和1.76μM的值，分别。这四名候选人已确定为β的进一步发展可能导致3-肾上腺素能受体激动剂用于肥胖症和II型糖尿病的药物治疗。游离OH和NH功能被发现是对β必不可少3 -肾上腺素能受体激动活性。中合成的β 3具有1,2,3,4-四氢喹啉骨架-肾上腺素能受体激动剂，所述Ñ苄基被发现是在优越Ñ -arylsulfonyl基。考虑到上述四个活性分子，已对假定的药效团模型进行了建模，这四个分子在活性和非活性分子之间有很好的区别。
• Forced nucleophilic substitution reaction of chlorobenzenes bearing electron-donating groups by the use of "naked" methoxide anion.
  作者：MINEO FUKUI、YUMIKO ENDO、TAKESHI OISHI

  DOI：10.1248/cpb.28.3639

  日期：——

  Nucleophilic aromatic substitution reactions of chlorobenzenes with the methoxide anion were found to proceed smoothly even in cases where electron-donating groups were present in the same aromatic ring when the chlorobenzenes were activated by chromium tricarbonyl complex formation and when the effectiveness of the methoxide anion was enhanced by the use of 18-crown-6. Application of the present method to indoline or tetrahydroquinoline systems was then examined and 5-chloro-1, 3, 3-trimethylindoline was successfully converted to the corresponding 5-methoxy or 5-benzyloxy compound.

  氯苯的亲核芳香取代反应与甲氧基阴离子的反应即使在同一芳香环中存在电子给体基团的情况下也能顺利进行，这是在氯苯通过铬三羰基配合物激活，并且通过使用18-冠-6增强甲氧基阴离子的有效性时进行的。随后，对该方法在吲哚啉或四氢喹啉体系中的应用进行了研究，并成功将5-氯-1, 3, 3-三甲基吲哚啉转化为相应的5-甲氧基或5-苄氧基化合物。
• Reductive Alkylation of Quinolines to <i>N</i>-Alkyl Tetrahydroquinolines Catalyzed by Arylboronic Acid
  作者：Priyanka Adhikari、Dipanjan Bhattacharyya、Sekhar Nandi、Pavan K. Kancharla、Animesh Das

  DOI：10.1021/acs.orglett.1c00302

  日期：2021.4.2

  A boronic acid catalyzed one-pot tandem reduction of quinolines to tetrahydroquinolines followed by reductive alkylation by the aldehyde has been demonstrated. This step-economcial synthesis of N-alkyl tetrahydroquinolines has been achieved directly from readily available quinolines, aldehydes, and Hantzsch ester under mild reaction conditions. The mechanistic study demonstrates the unique behavior

  已经证明了硼酸催化喹啉单锅串联还原为四氢喹啉，然后通过醛还原烷基化。N-烷基四氢喹啉的这种步骤经济的合成方法是在温和的反应条件下，从容易获得的喹啉，醛和汉茨酯直接完成的。机理研究证明了有机硼催化剂作为路易斯酸和氢键供体的独特行为。