3-(1-Benzyl-piperidin-4-yl)-propan-1-ol | 124438-29-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 3-(1-Benzyl-piperidin-4-yl)-propan-1-ol
• 英文别名: 3-(1-Benzylpiperidin-4-yl)propan-1-ol
• CAS: 124438-29-5
• 化学式: C₁₅H₂₃NO
• 分子量: 233.354
• InChiKey: IHRWMVVXSQATHL-UHFFFAOYSA-N

物化性质

• 沸点：
  343.3±15.0 °C(Predicted)
• 密度：
  1.026±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  23.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-(1-Benzyl-piperidin-4-yl)-propan-1-ol 在 palladium on activated charcoal 草酰氯 、 氰化钠 、 氨 、 甲酸铵 、 二甲基亚砜 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 为溶剂， 反应 29.75h， 生成 4-[2-(imidazol-4-yl)ethyl]piperidine
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of Conformationally Constrained Histamine H₃ Receptor Agonists

  摘要：

  Immepip, a conformationally constrained analogue of the histamine congener imbutamine, shows high affinity and functional activity on the human H-3 receptor. Using histamine and its homologues as prototypes, other rigid analogues containing either a piperidine or pyrrolidine ring in the side chain were synthesized and tested for their activities at the human H-3 receptor and the closely related H-4 receptor. In the series of piperidine containing analogues, immepip was found to be the most potent H-3 receptor agonist, whereas its propylene analogue 13a was identified as a high-affinity neutral antagonist for the human H-3 receptor. Moreover, replacement of the piperidine ring of immepip by a pyrrolidine ring led to a pair of enantiomers that show a distinct stereoselectivity at the human H-3 and H-4 receptor.

  DOI：

  10.1021/jm030905y
• 作为产物：
  描述：

  methyl 3-(1-benzylpiperidin-4-yl)propanoate 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以98%的产率得到3-(1-Benzyl-piperidin-4-yl)-propan-1-ol
  参考文献：
  名称：

  Synthesis, Biological Evaluation, and Molecular Modeling of Donepezil and N-[(5-(Benzyloxy)-1-methyl-1H-indol-2-yl)methyl]-N-methylprop-2-yn-1-amine Hybrids as New Multipotent Cholinesterase/Monoamine Oxidase Inhibitors for the Treatment of Alzheimer’s Disease

  摘要：

  A new family of multitarget molecules able to interact with acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), as well as with monoamino oxidase (MAO) A and B, has been synthesized. Novel compounds (3-9) have been designed using a conjunctive approach that combines the benzylpiperidine moiety of the AChE inhibitor donepezil (1) and the indolyl propargylamino moiety of the MAO inhibitor N-[(5-benzyloxy-1-methyl-1H-indol-2-yl)methyl]-N-methylprop-2-yn-1-amine (2), connected through an oligomethylene linker. The most promising hybrid (5) is a potent inhibitor of both MAO-A (IC50 = 5.2 +/- 1.1 nM) and MAO-B (IC50 = 43 +/- 8.0 nM) and is a moderately potent inhibitor of AChE (IC50 = 0.35 +/- 0.01 mu M) and BuChE (IC50 = 0.46 +/- 0.06 mu M). Moreover, molecular modeling and kinetic studies support the dual binding site to AChE, which explains the inhibitory effect exerted on A beta aggregation. Overall, the results suggest that the new compounds are promising multitarget drug candidates with potential impact for Alzheimer's disease therapy.

  DOI：

  10.1021/jm200853t

文献信息

• Novel pyridazinamine derivatives
  申请人：Janssen Pharmaceutica N.V.

  公开号：US04992433A1

  公开（公告）日：1991-02-12

  Novel pyridazinamine derivatives having antiviral activity, compositions containing these compounds as active ingredient, and a method of destructing viruses or preventing the growth thereof in warm-blooded animals suffering from diseases caused by these viruses. Processes for preparing said compounds and compositions.

  具有抗病毒活性的新型吡啶唑胺衍生物，含有这些化合物的组合物以及用所述化合物破坏或防止病毒生长的方法，用于治疗由这些病毒引起的疾病的温血动物。以及制备所述化合物和组合物的方法。
• Synthetic Study of 4-Substituted Piperidine Ring in Elarofiban, RWJ-50042, Tirofiban and Paroxetine
  作者：Meng-Yang Chang、John Yi-Chung Lin、Shui-Tein Chen、Nein-Chen Chang

  DOI：10.1002/jccs.200200156

  日期：2002.12

  A new strategy for synthesizing a 4-substituted piperidine ring uses the formal [3+3] cycloaddition reaction as the key protocol. This method provides a convenient formal synthesis of elarofiban, RWJ-50042, tirofiban and paroxetine.

  一种合成 4-取代哌啶环的新策略使用正式的 [3+3] 环加成反应作为关键方案。该方法提供了一种方便的正式合成 elarofiban、RWJ-50042、tirofiban 和帕罗西汀的方法。
• Synthesis, biological evaluation and molecular modeling studies of phthalazin-1(2H)-one derivatives as novel cholinesterase inhibitors
  作者：Noemí Vila、Pedro Besada、Dolores Viña、Mattia Sturlese、Stefano Moro、Carmen Terán

  DOI：10.1039/c6ra03841g

  日期：——

  A new series of donepezil analogues based on the phthalazin-1(2H)-one scaffold was designed and synthesized with the aim of exploring its potential as human ChEIs. Biological results revealed that the structural modifications proposed significantly affected ChE inhibitory potency as well as selectivity for AChE/BuChE. Compound 1d showed promising in vitro inhibition of both enzymes in the μM range

  设计并合成了一种新的基于酞菁-1（2 H）-一个支架的多奈哌齐类似物系列，旨在探索其作为人ChEIs的潜力。生物学结果表明，提出的结构修饰显着影响了ChE抑制能力以及对AChE / BuChE的选择性。化合物1d在μM范围内均显示出对这两种酶的体外抑制作用。但是，大多数目标化合物对AChE的活性均显着高于BuChE，特别是1f，1h和1j，IC 50。值在低微摩尔或亚微摩尔范围内，是系列中活性最高的化合物。对接模拟表明，活性最高的化合物可以使用类似的相互作用网络识别多奈哌齐结合位点。这些结果使我们能够合理化观察到的结构-活性关系。此外，预测的理化和ADME性质也与多奈哌齐相当。
• Donepezil-melatonin hybrids as butyrylcholinesterase inhibitors: Improving binding affinity through varying mode of linking fragments
  作者：Iwona Łozińska、Aleksandra Świerczyńska、Zuzanna Molęda、Alwin M. Hartman、Anna K. H. Hirsch、Zbigniew Czarnocki

  DOI：10.1002/ardp.201800194

  日期：2018.11

  Hybrid inhibitors of acetyl‐ and butyrylcholinesterase are compounds that combine structural motifs of two different classical inhibitors, leading to a dual binding ligand. A rapidly growing collection of those compounds involves a wide diversity of structural motifs, but the way of linking two active fragments and its impact on the affinity toward cholinesterases usually remains beyond the extent

  乙酰胆碱酯酶和丁酰胆碱酯酶的杂合抑制剂是结合了两种不同经典抑制剂的结构基序的化合物，从而形成双重结合配体。这些化合物的快速增长集合涉及广泛多样的结构基序，但连接两个活性片段的方式及其对胆碱酯酶亲和力的影响通常超出了研究范围。我们在此使用褪黑激素-多奈哌齐杂种对这方面进行详细分析。使用氨基甲酸酯接头连接两个片段的一系列新化合物对丁酰胆碱酯酶表现出出色的活性和选择性。
• Synthesis, biological assessment and molecular modeling of new multipotent MAO and cholinesterase inhibitors as potential drugs for the treatment of Alzheimer’s disease
  作者：Abdelouahid Samadi、Mourad Chioua、Irene Bolea、Cristóbal de los Ríos、Isabel Iriepa、Ignacio Moraleda、Agatha Bastida、Gerard Esteban、Mercedes Unzeta、Enrique Gálvez、José Marco-Contelles

  DOI：10.1016/j.ejmech.2011.05.048

  日期：2011.9

  The synthesis, biological evaluation and molecular modeling of new multipotent inhibitors of type I and type II, able to simultaneously inhibit monoamine oxidases (MAO) as well as acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), is described. Compounds of type I were prepared by sequential reaction of 2,6-dichloro-4-phenylpyridine-3,5-dicarbonitrile (14) [or 2,6-dichloropyridine-3,5-dicarbonitrile

  描述了能够同时抑制单胺氧化酶（MAO）以及乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BuChE）的新型I型和II型多功能抑制剂的合成，生物学评估和分子模型。通过使2,6-二氯-4-苯基吡啶-3,5-二甲腈（14）[或2,6-二氯吡啶-3,5-二甲腈（15）]与prop-2-依次反应来制备I型化合物炔-1-胺（或N-甲基丙-2-炔-1-胺）和2-（1-苄基哌啶-4-基）烷基胺22–25。II型化合物通过6-氨基-5-甲酰基-2-（甲基（丙-2-炔-1-基）氨基）烟腈32和33与4-（1-苄基哌啶-4-基）丁烷-的弗里德兰德型反应制备。2一（31）。分子1–11的生物学评估表明，这些化合物大多数在纳摩尔范围内都很有效，并具有选择性的AChEI，对MAO-A和MAO-B的抑制作用具有中等和均等的选择性。化合物8的动力学研究证明，它是Ee AChE混合型抑制剂（IC 50  = 16±2； Ki =