9-hydrazino-1,2,3,4-tetrahydroacridine | 65197-42-4

• 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: 9-hydrazino-1,2,3,4-tetrahydroacridine
• 英文别名: 9-Hydrazino-1,2,3,4-tetrahydroacridin；1,2,3,4-tetrahydroacridin-9-ylhydrazine
• CAS: 65197-42-4
• 化学式: C₁₃H₁₅N₃
• 分子量: 213.282
• InChiKey: DUEMTPVZWKGXAY-UHFFFAOYSA-N

物化性质

• 熔点：
  95-98 °C(Solv: ethyl acetate (141-78-6); hexane (110-54-3))
• 沸点：
  418.0±45.0 °C(Predicted)
• 密度：
  1.252±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  50.9
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  9-hydrazino-1,2,3,4-tetrahydroacridine 在 sodium tetrahydroborate 、 nickel dichloride 作用下， 以 甲醇 为溶剂， 反应 0.5h， 以86%的产率得到9-胺-1,2,3,4-四氢盐酸氯酯
  参考文献：
  名称：

  微波辅助合成4-喹啉基肼，然后还原硼化镍：一种方便的制备4-氨基喹啉及其衍生物的方法

  摘要：

  氯化镍（II）/硼氢化钠组合用于将4-肼基喹啉衍生物还原为相应的苯胺。该还原方案被有效地应用于单取代肼的还原裂解。我们在本文中描述了4-肼基喹啉的微波辅助合成，其提供了高产率和快速的两步法，用于在温和条件下合成4-氨基喹啉作为抗疟原体。

  DOI：

  10.1016/j.tetlet.2008.01.128
• 作为产物：
  描述：

  9-氯-1,2,3,4-四氢吖啶 在 一水合肼 作用下， 反应 0.08h， 以88%的产率得到9-hydrazino-1,2,3,4-tetrahydroacridine
  参考文献：
  名称：

  微波辅助合成4-喹啉基肼，然后还原硼化镍：一种方便的制备4-氨基喹啉及其衍生物的方法

  摘要：

  氯化镍（II）/硼氢化钠组合用于将4-肼基喹啉衍生物还原为相应的苯胺。该还原方案被有效地应用于单取代肼的还原裂解。我们在本文中描述了4-肼基喹啉的微波辅助合成，其提供了高产率和快速的两步法，用于在温和条件下合成4-氨基喹啉作为抗疟原体。

  DOI：

  10.1016/j.tetlet.2008.01.128

文献信息

• Design, Synthesis, and Structure–Activity Relationship Studies of 4-Quinolinyl- and 9-Acrydinylhydrazones as Potent Antimalarial Agents
  作者：Caterina Fattorusso、Giuseppe Campiani、Gagan Kukreja、Marco Persico、Stefania Butini、Maria Pia Romano、Maria Altarelli、Sindu Ros、Margherita Brindisi、Luisa Savini、Ettore Novellino、Vito Nacci、Ernesto Fattorusso、Silvia Parapini、Nicoletta Basilico、Donatella Taramelli、Vanessa Yardley、Simon Croft、Marianna Borriello、Sandra Gemma

  DOI：10.1021/jm7012375

  日期：2008.3.13

  synthesis, and biological investigation of novel antimalarial agents with low potential to develop resistance and structurally based on a highly conjugated scaffold. Starting from a new hit, the designed modifications were performed hypothesizing a specific interaction with free heme and generation of radical intermediates. This approach provided antimalarials with improved potency against chloroquine-resistant

  疟疾是贫困地区的主要健康问题，在这些地区，人们迫切需要以负担得起的价格购买新的抗寄生虫药。我们在此报告了新型抗疟疾药物的设计，合成和生物学研究，这些药物具有发展抗药性的低潜力，并且在结构上基于高度偶联的支架。从新的命中开始，进行设计的修饰，假设与游离血红素发生特定的相互作用并产生自由基中间体。与已知药物相比，该方法为抗疟药提供了增强的抗氯喹抗疟原虫能力。确定了许多结构-活性关系（SAR）趋势，在合成的类似物中，吡咯烷基甲基亚芳基和咪唑衍生物5r，5t，发现8b和8b是新系列中最有效的抗疟药。研究了新化合物的作用机理，并评估了它们的体内活性。
• Intracellular distribution of new tacrine analogues as a potential cause of their cytotoxicity against human neuroblastoma cells SH-SY5Y
  作者：Krajňáková Lucia、Pisarčiková Jana、Drajna Ladislav、Labudová Martina、Imrich Ján、Paulíková Helena、Kožurková Mária

  DOI：10.1007/s00044-018-2241-6

  日期：2018.10

  ]acetate (4) were synthesized and their characteristics were investigated. All of the novel derivatives were found to inhibit acetylcholinesterase obtained from Electrophorus electricus at a magnitude of one order less than that of the control tacrine. Derivatives 1–3 were found to be nontoxic towards human neuroblastoma SH-SY5Y cells, while compound 4 was markedly cytotoxic against these cells (IC50

  四种新的与糖结合的他克林衍生物，4-（2,3,4,6-四-O-乙酰基-β - D-吡喃葡萄糖基）-1-（1,2,3,4-四氢ac啶-9-基）硫代氨基脲（1），4-（2,3,4,6-四-O-乙酰基-β - D-甘露吡喃糖基）-1-（1,2,3,4-四氢ac啶-9-基）硫代氨基脲（2）， 2'-（1,2,3,4-四氢ac啶-9-基）肼基-3'-（2,3,4,6-四-O-乙酰基-β - D-吡喃半乳糖基）-1'，3'噻唑烷-4'-酮（3）和[2' - （1,2,3,4-四氢吖啶-9-基）亚肼基-3' - （2,3,4,6-四- ø -乙酰基-β - D合成了（-吡喃葡萄糖基）-4'-氧噻唑烷-5-乙酸酯（4），并研究了它们的特性。发现所有这些新的衍生物抑制自电泳获得的乙酰胆碱酯酶的量比对照他克林的量少一阶。衍生物1 - 3被认为是对人神经母SH-SY5Y细胞无毒的，而化合物4是对这些细胞的细胞毒性显着（IC
• Quinolylhydrazones as novel inhibitors of Plasmodium falciparum serine protease PfSUB1
  作者：Sandra Gemma、Simone Giovani、Margherita Brindisi、Pierangela Tripaldi、Simone Brogi、Luisa Savini、Isabella Fiorini、Ettore Novellino、Stefania Butini、Giuseppe Campiani、Maria Penzo、Michael J. Blackman

  DOI：10.1016/j.bmcl.2012.06.023

  日期：2012.8

  Plasmodium falciparum subtilisin-like protease 1 (PfSUB1) is a serine protease that plays key roles in the egress of the parasite from red blood cells and in preparing the released merozoites for the subsequent invasion of new erythrocytes. The development of potent and selective PfSUB1 inhibitors could pave the way to the discovery of potential antimalarial drugs endowed with an innovative mode of action and consequently able to overcome the current problems of resistance to established chemotherapies. Through the screening of a proprietary library of compounds against PfSUB1, we identified hydrazone 2 as a hit compound. Here we report a preliminary investigation of the structure-activity relationships for a class of PfSUB1 inhibitors related to our identified hit. (C) 2012 Elsevier Ltd. All rights reserved.
• Targeting clinically-relevant metallo-<b>β</b>-lactamases: from high-throughput docking to broad-spectrum inhibitors
  作者：Margherita Brindisi、Simone Brogi、Simone Giovani、Sandra Gemma、Stefania Lamponi、Filomena De Luca、Ettore Novellino、Giuseppe Campiani、Jean-Denis Docquier、Stefania Butini

  DOI：10.3109/14756366.2016.1172575

  日期：2016.11.1

  Metallo-beta-lactamases (MBLs) represent one of the most important and widespread mechanisms of resistance to beta-lactam antibiotics (including the life-saving carbapenems), against which no clinically useful inhibitors are currently available. We report herein a structure-based high-throughput docking (HTD) campaign on three clinically-relevant acquired MBLs (IMP-1, NDM-1 and VIM-2). The initial hit NF1810 (1) was optimized providing the broad-spectrum inhibitor 3i, which is able to potentiate the in vitro activity of cefoxitin on a VIM-2-producing E. coli strain.
• Discovery of potent nucleotide-mimicking competitive inhibitors of hepatitis C virus NS3 helicase
  作者：Sandra Gemma、Stefania Butini、Giuseppe Campiani、Margherita Brindisi、Samantha Zanoli、Maria Pia Romano、Pierangela Tripaldi、Luisa Savini、Isabella Fiorini、Giuseppe Borrelli、Ettore Novellino、Giovanni Maga

  DOI：10.1016/j.bmcl.2010.09.002

  日期：2011.5

  Among the enzymes involved in the life cycle of HCV, the non-structural protein NS3, with its double function of protease and NTPase/helicase, is essential for the virus replication. Exploiting our previous knowledge in the development of nucleotide-mimicking NS3 helicase (NS3h) inhibitors endowed with key structural and electronic features necessary for an optimal ligand-enzyme interaction, we developed the tetrahydroacridinyl derivative 3a as the most potent NS3h competitive inhibitor reported to date (HCV NS3h K(i) = 20 nM). (C) 2010 Elsevier Ltd. All rights reserved.