2-(1-苄基哌啶-4-基)乙醛 | 120014-32-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 2-(1-苄基哌啶-4-基)乙醛
• 英文名称: 2-(1-benzylpiperidin-4-yl)acetaldehyde
• 英文别名: (1-benzylpiperidin-4-yl)acetaldehyde；4-Piperidineacetaldehyde, 1-(phenylmethyl)-
• CAS: 120014-32-6
• 化学式: C₁₄H₁₉NO
• 分子量: 217.311
• InChiKey: MHGRPEADXUSKAT-UHFFFAOYSA-N

物化性质

• 沸点：
  322.0±15.0 °C(Predicted)
• 密度：
  1.031±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(1-苄基哌啶-4-基)乙醛 以 甲醇 为溶剂， 反应 1.0h， 生成 N-[2-(1-benzylpiperidin-4-yl)ethyl]prop-2-yn-1-amine
  参考文献：
  名称：

  Donepezil + propargylamine + 8-hydroxyquinoline hybrids as new multifunctional metal-chelators, ChE and MAO inhibitors for the potential treatment of Alzheimer's disease

  摘要：

  The synthesis, biochemical evaluation, ADMET, toxicity and molecular modeling of novel multi-target-directed Donepezil + Propargylamine + 8-Hydroxyquinoline (DPH) hybrids 1-7 for the potential prevention and treatment of Alzheimer's disease is described. The most interesting derivative was racemic α-aminotrile4-(1-benzylpiperidin-4-yl)-2-(((8-hydroxyquinolin-5-yl)methyl)(prop-2-yn-1-yl)amino) butanenitrile (DPH6) [MAO A (IC50 = 6.2 ± 0.7 μM; MAO B (IC50 = 10.2 ± 0.9 μM); AChE (IC50 = 1.8 ± 0.1 μM); BuChE (IC50 = 1.6 ± 0.25 μM)], an irreversible MAO A/B inhibitor and mixed-type AChE inhibitor with metal-chelating properties. According to docking studies, both DPH6 enantiomers interact simultaneously with the catalytic and peripheral site of EeAChE through a linker of appropriate length, supporting the observed mixed-type AChE inhibition. Both enantiomers exhibited a relatively similar position of both hydroxyquinoline and benzyl moieties with the rest of the molecule easily accommodated in the relatively large cavity of MAO A. For MAO B, the quinoline system was hosted at the cavity entrance whereas for MAO A this system occupied the substrate cavity. In this disposition the quinoline moiety interacted directly with the FAD aromatic ring. Very similar binding affinity values were also observed for both enantiomers with ChE and MAO enzymes. DPH derivatives exhibited moderate to good ADMET properties and brain penetration capacity for CNS activity. DPH6 was less toxic than donepezil at high concentrations; while at low concentrations both displayed a similar cell viability profile. Finally, in a passive avoidance task, the antiamnesic effect of DPH6 was tested on mice with experimentally induced amnesia. DPH6 was capable to significantly decrease scopolamine-induced learning deficits in healthy adult mice.

  DOI：

  10.1016/j.ejmech.2014.04.078
• 作为产物：
  描述：

  1-苄基-4-哌啶甲醛 在 盐酸 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 反应 38.58h， 生成 2-(1-苄基哌啶-4-基)乙醛
  参考文献：
  名称：

  Novel piperidine .sigma. receptor ligands as potential antipsychotic drugs

  摘要：

  Sigma receptor ligands represent a new class of potential antipsychotic drugs. This paper presents the structure-activity relationships leading to novel disubstituted piperidine sigma ligands, which have little or no affinity for dopamine D2 receptors. Selectivity for sigma sites over dopamine D2 or serotonin 5-HT2 receptors appears to be governed by the chemical nature of the piperidine nitrogen substituent, its distance from the basic nitrogen, and its orientation relative to the other piperidine substituent. Several of these compounds have good oral potency in some animal models used to evaluate potential antipsychotic drugs. The N-cyclopropylmethyl ketones and ethers (e.g. 6i (DuP 734), 6q, 18a, and 18n) have the best in vivo potency. Compounds 6i (DuP 734) and 6q did not cause catalepsy in the rat, even at very high doses. On the basis of the pharmacology profiles of these sigma ligands, we propose these compounds may be effective antipsychotic drugs, which do not induce extrapyramidal side effects or tardive dyskinesia.

  DOI：

  10.1021/jm00101a012
• 作为试剂：
  描述：

  邻溴氟苯 、 正丁基锂 、 2-(1-苄基哌啶-4-基)乙醛 、 水 在 2-(1-苄基哌啶-4-基)乙醛 、 水 、 Brine 、 magnesium sulfate 、 silica gel 、 ethyl acetate n-hexane 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以to obtain the title compound (2.15 g, 60% yield)的产率得到2-(1-Benzylpiperidin-4-yl)-1-(2-fluorophenyl)ethanol
  参考文献：
  名称：

  Nitrogen containing heterocyclic compounds and medicines containing the same

  摘要：

  下列通式所代表的化合物：1（其中X1，X2，X3和X4各自独立地代表单键，C1-6烷基等；A2代表可选取代的苯基等；A1代表可选取代的5-至7-成员的杂环基，包含-C（═Q1）-（其中Q1代表氧、硫或═N—R11（其中R11代表氢或C1-6烷基））和氮等；Z1代表哌啶基等），其盐和水合物。

  公开号：

  US20040167224A1

文献信息

• Novel piperidine compouds and drugs containing the same
  申请人：——

  公开号：US20030220368A1

  公开（公告）日：2003-11-27

  The present invention provides a novel compound having a superior Na + channel inhibition activity. Namely, it provides a compound represented by the following formula (I), a salt thereof or a hydrate of them. 1 In the formula, the ring A represents a ring represented by the formula: 2 (wherein R 1 represents a hydrogen atom etc.; and R 2 represents indicates a hydrogen atom and the like) etc.; W represents an optionally substituted C 1-6 alkylene group etc.; Z represents an optionally substituted C 6-14 aromatic hydrocarbon cyclic group etc.; and l represents an integer from 0 to 6.

  本发明提供了一种具有优越的Na + 通道抑制活性的新型化合物。即提供了由以下式（I）表示的化合物，其盐或其水合物。 在该式中，环A表示由以下式表示的环： （其中R 1 表示氢原子等；R 2 表示表示氢原子等）等；W表示可选地取代的C 1-6 烷基等；Z表示可选地取代的C 6-14 芳香烃环基等；l表示0到6的整数。
• Design and synthesis of N-benzylpiperidine–purine derivatives as new dual inhibitors of acetyl- and butyrylcholinesterase
  作者：María Isabel Rodríguez-Franco、María Isabel Fernández-Bachiller、Concepción Pérez、Ana Castro、Ana Martínez

  DOI：10.1016/j.bmc.2005.07.019

  日期：2005.12

  used in the design of more potent N-benzylpiperidine inhibitors bearing an 8-substituted caffeine fragment and a methoxymethyl linker. These new compounds are interesting dual inhibitors of acetylcholinesterase and butyrylcholinesterase and have been chosen for further optimisation.

  描述了N-苄基-（哌啶或吡咯烷基）-嘌呤的合成和生物学评估。衍生自N-苄基哌啶和N-取代嘌呤的化合物显示出中等的乙酰胆碱酯酶抑制作用。初步的结构活性关系和最佳化合物与多奈哌齐的活性构象的叠加已揭示了结构特征，这些结构特征已用于设计更有效的带有8个取代的咖啡因片段和甲氧基甲基接头的N-苄基哌啶抑制剂。这些新化合物是有趣的乙酰胆碱酯酶和丁酰胆碱酯酶的双重抑制剂，已被选择用于进一步优化。
• [EN] PYRAZINE COMPOUNDS AS PHOSPHODIESTERASE 10 INHIBITORS<br/>[FR] COMPOSES DE PYRAZINE COMME INHIBITEURS DE PHOSPHODIESTERASE 10
  申请人：AMGEN INC

  公开号：WO2010057121A1

  公开（公告）日：2010-05-20

  Pyrazine compounds, and compositions containing them, and processes for preparing such compounds. Provided herein also are methods of treating disorders or diseases treatable by inhibition of PDE10, such as obesity, non-insulin dependent diabetes, schizophrenia, bipolar disorder, obsessive-compulsive disorder, and the like.

  吡嗪化合物、含有它们的组合物以及制备这些化合物的方法。还提供了通过抑制PDE10治疗可治疗的疾病或病症的方法，例如肥胖、非胰岛素依赖型糖尿病、精神分裂症、双相情感障碍、强迫症等。
• Triazole containing indole derivatives
  申请人：Merck Sharp & Dohme Limited

  公开号：US05298520A1

  公开（公告）日：1994-03-29

  A class of substituted imidazole, triazole and tetrazole derivatives are selective agonists of 5-HT.sub.1 -like receptors and are therefore useful in the treatment of clinical conditions, in particular migraine and associated disorders, for which a selective agonist of these receptors is indicated.

  一类取代的咪唑、三唑和四唑衍生物是5-HT.sub.1 -样受体的选择性激动剂，因此在治疗临床疾病中特别有用，尤其是偏头痛和相关的紊乱，对于这些疾病，需要使用这些受体的选择性激动剂。
• Novel piperidine derivatives. Synthesis and anti-acetylcholinesterase activity of 1-benzyl-4-[2-(N-benzoylamino)ethyl]piperidine derivatives
  作者：Hachiro Sugimoto、Yutaka Tsuchiya、Hiroyuki Sugumi、Kunizo Higurashi、Norio Karibe、Yoichi Iimura、Atsushi Sasaki、Yoshiyuki Kawakami、Takaharu Nakamura

  DOI：10.1021/jm00169a008

  日期：1990.7

  to play an important role in the increased activity, since the N-benzoylpiperidine derivative was almost inactive. We found that 1-benzyl-4-[2-(N-[4'-(benzylsulfonyl) benzoyl]-N-methylamino]ethyl]piperidine hydrochloride (21) (IC50 = 0.56 nM) is one of the most potent inhibitors of acetylcholinesterase. Compound 21 showed an affinity 18,000 times greater for AChE than for BuChE. At a dose of 3 mg/kg

  合成了一系列的1-苄基-4- [2-（N-苯甲酰基氨基）乙基]哌啶衍生物，并评估了其抗乙酰胆碱酯酶（anti-AChE）的活性。用对位上的大体积部分取代苯甲酰胺导致活性显着增加。在苯甲酰胺的氮原子上引入烷基或苯基大大增强了活性。哌啶氮原子的基本质量似乎在活性增加中起重要作用，因为N-苯甲酰基哌啶衍生物几乎没有活性。我们发现1-苄基-4- [2-（N- [4'-（苄基磺酰基）苯甲酰基] -N-甲基氨基]乙基]哌啶盐酸盐（21）（IC50 = 0.56 nM）是最有效的抑制剂之一化合物21对AChE的亲和力比对BuChE的亲和力大18,000倍，剂量为3 mg / kg时，21在大鼠的脑涡和海马中产生了乙酰胆碱（ACh）含量的显着显着增加。选择化合物21作为抗痴呆剂进行高级开发。