6-chlorotacrine | 5778-84-7

• 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: 6-chlorotacrine
• 英文别名: 6-chloro-1,2,3,4-tetrahydroacridin-9-amine；9-amino-6-chloro-1,2,3,4-tetrahydroacridine；chlorotacrine；9-Amino-6-chloro-1,2,3,4-tetrahydro-acridine
• CAS: 5778-84-7
• 化学式: C₁₃H₁₃ClN₂
• 分子量: 232.713
• InChiKey: GQZMDBQRGRRPMS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  38.9
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-chlorotacrine 在 氢溴酸 、 potassium hydroxide 作用下， 以 甲醇 、 水 、 二甲基亚砜 为溶剂， 生成 9-[(10-bromodecyl)amino]-6-chloro-1,2,3,4-tetrahydroacridine hydrobromide
  参考文献：
  名称：

  Huprine-他克林异二聚体作为抗淀粉样蛋白的化合物，可能对阿尔茨海默氏症和Pri病毒病具有重要意义

  摘要：

  已经开发了一个胡珀林-他克林异二聚体家族，可以同时阻断乙酰胆碱酯酶（AChE）的活性位点和周围位点。它们与AChE的双重位点结合，得到动力学和分子模型研究的支持，导致高度有效地抑制人AChE的催化活性，更重要的是，在体外中和了AChE对两者聚集的病理伴侣作用β-淀粉样肽（Aβ）和a蛋白肽在the蛋白的聚集中起关键作用。Huprine-Tacrine异二聚体具有附加价值，因为它们在体外对人的丁酰胆碱酯酶，自身诱导的Aβ聚集和β-分泌酶显示出有效的抑制活性。最后，他们能够穿越血脑屏障，如在人工膜模型试验中预测的那样，并在OF1小鼠的离体实验中得到证实，达到了它们在中枢神经系统中的多个生物学靶标。总体而言，这些化合物是用于治疗阿尔茨海默氏病和病毒疾病的有前途的先导化合物。

  DOI：

  10.1021/jm200840c
• 作为产物：
  描述：

  6-氯-9-肼基-1,2,3,4-四氢吖啶 在 sodium tetrahydroborate 、 nickel(II) chloride hexahydrate 作用下， 反应 1.0h， 以56%的产率得到6-chlorotacrine
  参考文献：
  名称：

  Functionalized acridin-9-yl phenylamines protected neuronal HT22 cells from glutamate-induced cell death by reducing intracellular levels of free radical species

  摘要：

  The in vitro neuronal cell death model based on the HT22 mouse hippocampal cell model is a convenient means of identifying compounds that protect against oxidative glutamate toxicity which plays a role in the development of certain neurodegenerative diseases. Functionalized acridin-9-yl-phenylamines were found to protect HT22 cells from glutamate challenge at submicromolar concentrations. The Aryl(1)-NH-Aryl(2) scaffold that is embedded in these compounds was the minimal pharmacophore for activity. Mechanistically, protection against the endogenous oxidative stress generated by glutamate did not involve up-regulation of glutathione levels but attenuation of the late stage increases in mitochondrial ROS and intracellular calcium levels. The NH residue in the pharmacophore played a crucial role in this regard as seen from the loss of neuroprotection when it was structurally modified or replaced. That the same NH was essential for radical scavenging in cell-free and cell-based systems pointed to an antioxidant basis for the neuroprotective activities of these compounds. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.02.006

文献信息

• The Divergent Transformations of Aromatic<i>o</i>-Aminonitrile with Carbonyl Compound
  作者：Jianhong Tang、Jiarong Li、Lijun Zhang、Shuling Ma、Daxin Shi、Qi Zhang、Liupan Yang、Xiuzhen Wang、Xuan Liu、Change Liu

  DOI：10.1002/jhet.804

  日期：2012.5

  A modified Friedländer conversion of the cyclocondensation of aromatic o‐aminonitriles with carbonyl compounds was discovered. Systematic studies reveal that both the new transformation and the classic Friedländer annulation in the presence of ZnCl2 constitute a pair of divergent reaction, and thecontrolled PDF transformation of this divergent reaction was achieved in the present of bases.

  发现了芳族邻氨基腈与羰基化合物的环缩合反应的改进的Friedländer转化。系统研究表明，在存在ZnCl 2的情况下，新的转化和经典的Friedländer圆环构成了一对发散反应，并且在碱的存在下实现了该发散反应的受控PDF转化。
• SAR of 9-Amino-1,2,3,4-tetrahydroacridine-Based Acetylcholinesterase Inhibitors:  Synthesis, Enzyme Inhibitory Activity, QSAR, and Structure-Based CoMFA of Tacrine Analogues
  作者：Maurizio Recanatini、Andrea Cavalli、Federica Belluti、Lorna Piazzi、Angela Rampa、Alessandra Bisi、Silvia Gobbi、Piero Valenti、Vincenza Andrisano、Manuela Bartolini、Vanni Cavrini

  DOI：10.1021/jm990971t

  日期：2000.5.1

  the substituents in position 7 of tacrine and (b) a tentative assignment of the hydrophobic character to the favorable effect exerted by the substituents in position 6. Finally, a new previously unreported tacrine derivative designed on the basis of both the classical and the 3D QSAR equations was synthesized and kinetically evaluated, to test the predictive ability of the QSAR models. The 6-bromo-9-amino-1

  在这项研究中，我们试图获得与他克林有关的乙酰胆碱酯酶（AChE）抑制剂类别的综合SAR图像，他克林是目前用于治疗阿尔茨海默氏病的药物。为此，我们合成并测试了一系列9-氨基-1,2,3,4-四氢ac啶衍生物，这些衍生物在the啶核的6和7位上取代，并在9-氨基官能团上带有选定的基团。通过Hansch方法，获得了QSAR方程，定量考虑了位置7的取代基的有害空间效应和9-氨基-1,2位置6和7的取代基所施加的有利的电子吸引作用， 3，4-四氢ac啶衍生物。通过对由12个9-氨基-1,2,3,4-四氢ac啶和13个11H-茚三酮制得的一系列AChE抑制剂进行CoMFA分析，考虑了抑制剂的三维（3D）特性。以前在我们实验室开发的2-b] quinolin-10-ylamines。通过利用对接模型计算待提交CoMFA程序的分子的比对，该模型针对未取代的9-氨基-1,2,3,4-四氢ac啶和11H-茚并[1
• Synthesis of tacrine derivatives under solventless conditions
  作者：Mohammad A. Khalilzadeh、Abolfazl Hosseini、Mahmoud Tajbakhsh

  DOI：10.1002/jhet.5570440305

  日期：2007.5

  the solid-phase synthesis of tacrine and its derivatives have been evaluated. Preparation of tacrine analogues under conventional conditions suffers from poor synthetic efficiency and usually gives low yield. Reaction of substituted anthranilonitrile with cyclohexanone under microwave irradiation gave a good to excellent yield of the corresponding substituted 9-amino-1,2,3,4-tetrahydroacridines.

  已经评估了微波辐射对他克林及其衍生物的固相合成的影响。在常规条件下制备他克林类似物的合成效率差，通常收率低。在微波辐射下，取代的蒽腈与环己酮的反应得到相应的取代的9-氨基-1,2,3,4-四氢ac啶的良好至优异的产率。
• Synthesis of quinolines via Friedländer reaction catalyzed by CuBTC metal–organic-framework
  作者：Elena Pérez-Mayoral、Zuzana Musilová、Barbara Gil、Bartosz Marszalek、Miroslav Položij、Petr Nachtigall、Jiri Čejka

  DOI：10.1039/c2dt11978a

  日期：——

  Friedländer condensation between 2-aminoaryl ketones and different carbonyl compounds, catalyzed by CuBTC was investigated by a combination of various experimental techniques and by density functional theory based modelling. CuBTC exhibiting hard Lewis acid character showed highly improved catalytic activity when compared with other molecular sieves showing high concentraion of Lewis acid sites, e.g. in BEA and (Al)SBA-15. Polysubstituted quinolines were synthesized via a Friedländer reaction catalyzed by CuBTC under the solvent-free conditions. High concentration of active sites in CuBTC together with the concerted effect of a pair of adjacent Cu2+ coordinatively unsaturated active sites are behind a very high quinoline yield reached within a short reaction time. Results reported here make CuBTC a promising catalyst for other Lewis acid-promoted condensations, including those leading to biologically active compounds with a particular relevance for the pharmaceutical industry. The mechanism of a catalyzed Friedländer reaction investigated computationally is also reported.

  对Friedländer缩聚反应在2-氨基芳基酮和不同羰基化合物之间，采用CuBTC作为催化剂的研究，结合了多种实验技术和基于密度泛函理论的建模。具有硬路易斯酸特性的CuBTC展现出了比其他分子筛（如BEA和(Al)SBA-15，它们的路易斯酸位点浓度高）更高的催化活性。在无溶剂条件下，通过CuBTC催化的Friedländer反应合成了多取代喹啉。CuBTC中高浓度的活性位点以及相邻的一对配位不饱和的Cu2+活性位点的协同效应，是其在一小段时间内达到极高喹啉产率的原因。这里报告的结果使CuBTC成为其他路易斯酸促进缩聚反应的有力催化剂，包括那些导致生物活性化合物产生的反应，对制药行业具有特别重要意义。同时，还报告了通过计算研究得出的催化Friedländer反应的机理。
• Heterodimers and Methods of Using Them
  申请人：IP Nancy Y.

  公开号：US20080176308A1

  公开（公告）日：2008-07-24

  Novel heterodimers of tetrahydroacridines and tetrahydroquinolinones are disclosed. The heterodimers are capable of acting as both acetylcholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists. The heterodimers may be used to improve cognitive defects via treatment or prevention in both humans and non-humans.

  揭示了新型四氢喹啉和四氢喹啉酮的异源二聚体。这些异源二聚体能够同时作为乙酰胆碱酯酶抑制剂和N-甲基-D-天冬氨酸（NMDA）受体拮抗剂。这些异源二聚体可用于改善人类和非人类的认知缺陷，通过治疗或预防。