Methyl 1-(4-fluorobenzyl)-4-oxo-3-piperidinecarboxylate | 1225545-54-9

• 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: Methyl 1-(4-fluorobenzyl)-4-oxo-3-piperidinecarboxylate
• 英文别名: methyl 1-[(4-fluorophenyl)methyl]-4-oxopiperidine-3-carboxylate
• CAS: 1225545-54-9
• 化学式: C₁₄H₁₆FNO₃
• 分子量: 265.284
• InChiKey: FAJCXWAHWVDORO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Methyl 1-(4-fluorobenzyl)-4-oxo-3-piperidinecarboxylate 在 盐酸 、 水 、 sodium hydroxide 作用下， 生成 1-(4-Fluorobenzyl)-4-piperidone
  参考文献：
  名称：

  N-（取代的苄基）-3,5-双（亚苄基）-4-哌啶酮：合成和初步抗白血病活性（I）

  摘要：

  通过一系列的迈克尔加成，狄克曼缩合，水解脱羧和羟醛缩合反应，以取代的苄胺为原料合成了一系列新颖的N-（取代的苄基）-3,5-双（亚苄基）-4-哌啶酮5a - 5o。通过1 H NMR，IR，MS技术和元素分析确认了结构。使用白血病细胞系K562进行的基于分析的抗增殖活性研究表明，大多数标题化合物具有抑制白血病K562细胞增殖的高效率，其中化合物5g（IC 50 = 7.81 µg·mL -1），5k（IC 50 = 6.35微克·毫升-1），5l（IC 50 = 7.20 µg·mL -1）和5o（IC 50 = 5.79 µg·mL -1）具有比标准5-氟尿嘧啶（IC 50 = 8.56 µg·mL -1）更好的抑制活性。

  DOI：

  10.1002/cjoc.201180365
• 作为产物：
  描述：

  Methyl 3-[(4-fluorophenyl)methyl-(3-methoxy-3-oxopropyl)amino]propanoate 在 sodium methylate 作用下， 以 甲醇 、 甲苯 为溶剂， 生成 Methyl 1-(4-fluorobenzyl)-4-oxo-3-piperidinecarboxylate
  参考文献：
  名称：

  Novel 2H-pyrazolo[4,3-c]hexahydropyridine derivatives: Synthesis, crystal structure, fluorescence properties and cytotoxicity evaluation against human breast cancer cells

  摘要：

  一系列新型2H-吡唑[4,3-c]六氢吡啶衍生物（II）已被设计和合成。目标化合物通过元素分析和光谱（1H NMR、IR和MS）数据得到确认，化合物（II 1）的绝对构型通过单晶X射线衍射法得以确认。对目标化合物在体外针对两个人乳腺癌细胞株MCF-7和MDA-MB-231进行了MTT法评估其细胞毒性。大多数化合物表现出良好的抑制作用，其中化合物II 21（对MCF-7的IC50为4.7 μM，對MDA-MB-231的IC50为9.3 μM）、II 33（对MCF-7的IC50为2.4 μM，對MDA-MB-231的IC50为4.2 μM）和II 40（对MCF-7的IC50为3.3 μM，對MDA-MB-231的IC50为8.6 μM）显示出比5-氟尿嘧啶（对MCF-7的IC50为4.8 μM，對MDA-MB-231的IC50为9.6 μM）更好的抑制活性。流式细胞仪分析和DNA片段化结果表明，II 33具有细胞毒性，并能诱导MCF-7细胞的凋亡。还研究了化合物II 1、II 6、II 11、II 16、II 23、II 28和II 35的荧光特性，其中化合物II 28的光致发光量子产率最高（38%）。

  DOI：

  10.1007/s11426-013-4840-x

文献信息

• N-(Substituted benzyl)-3,5-bis(benzylidene)-4-piperidones: Synthesis and Preliminary Anti-leukemia Activity (I)
  作者：Jing Wang、Wen Meng、Zhenjie Ni、Sijia Xue

  DOI：10.1002/cjoc.201180365

  日期：2011.10

  A series of novel N‐(substituted benzyl)‐3,5‐bis(benzylidene)‐4‐piperidones 5a–5o were synthesized with substituted benzylamines as raw materials via a series of Michael addition, Dieckmann condensation, hydrolysis decarboxylation and aldol condensation. The structures were confirmed by 1H NMR, IR, MS techniques and elemental analysis. Assay‐based antiproliferative activity study using leukemic cell

  通过一系列的迈克尔加成，狄克曼缩合，水解脱羧和羟醛缩合反应，以取代的苄胺为原料合成了一系列新颖的N-（取代的苄基）-3,5-双（亚苄基）-4-哌啶酮5a - 5o。通过1 H NMR，IR，MS技术和元素分析确认了结构。使用白血病细胞系K562进行的基于分析的抗增殖活性研究表明，大多数标题化合物具有抑制白血病K562细胞增殖的高效率，其中化合物5g（IC 50 = 7.81 µg·mL -1），5k（IC 50 = 6.35微克·毫升-1），5l（IC 50 = 7.20 µg·mL -1）和5o（IC 50 = 5.79 µg·mL -1）具有比标准5-氟尿嘧啶（IC 50 = 8.56 µg·mL -1）更好的抑制活性。
• Novel Hits in the Correction of ΔF508-Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Protein: Synthesis, Pharmacological, and ADME Evaluation of Tetrahydropyrido[4,3-<i>d</i>]pyrimidines for the Potential Treatment of Cystic Fibrosis
  作者：Elisabetta Pesci、Laura Bettinetti、Paola Fanti、Luis J. V. Galietta、Salvatore La Rosa、Letizia Magnoni、Nicoletta Pedemonte、Gian Luca Sardone、Laura Maccari

  DOI：10.1021/acs.jmedchem.5b00771

  日期：2015.12.24

  Cystic fibrosis (CF) is a lethal genetic disease caused by mutations of the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) with a prevalence of the Delta F508 mutation. Whereas the detailed mechanisms underlying disease have yet to be fully elucidated, recent breakthroughs in clinical trials have demonstrated that CFTR dysfunction can be corrected by drug-like molecules. On the basis of this success, a screening campaign was carried out, seeking new drug-like compounds able to rescue Delta F508-CFTR that led to the discovery of a novel series of correctors based on a tetrahydropyrido[4,3-d]pyrimidine core. These molecules proved to be soluble, cell-permeable, and active in a disease relevant functional-assay. The series was then further optimized with emphasis on biological data from multiple cell systems while keeping physicochemical properties under strict control. The pharmacological and ADME profile of this corrector series hold promise for the development of more efficacious compounds to be explored for therapeutic use in CF.
• Novel 2H-pyrazolo[4,3-c]hexahydropyridine derivatives: Synthesis, crystal structure, fluorescence properties and cytotoxicity evaluation against human breast cancer cells
  作者：ChunCheng Pang、ChuanWen Sun、Jing Wang、Di Xiao、Li Ding、HongFei Bu

  DOI：10.1007/s11426-013-4840-x

  日期：2013.6

  A series of novel 2H-pyrazolo[4,3-c]hexahydropyridine derivatives (II) have been designed and synthesized. The target compounds have been identified by elemental analysis and spectral (1H NMR, IR, and MS) data and the absolute configuration of compound (II 1 ) was confirmed by single crystal X-ray diffraction. The cytotoxicity of the target compounds have been evaluated in vitro against two human breast cancer cell lines MCF-7 and MDA-MB-231 by MTT assay. Most compounds exhibited good inhibition, and compounds II 21 (IC50 = 4.7 μM for MCF-7 and IC50 = 9.3 μM for MDA-MB-231), II 33 (IC50 = 2.4 μM for MCF-7 and IC50 = 4.2 μM for MDA-MB-231) and II 40 (IC50 = 3.3 μM for MCF-7 and IC50 =8.6 μM for MDA-MB-231) displayed better inhibitory activity than 5-fluorouracil (IC50 = 4.8 μM for MCF-7 and IC50 = 9.6 μM for MDA-MB-231, respectively). Flow cytometric analysis and DNA fragmentation suggest that II 33 is cytotoxic and able to induce the apoptosis of MCF-7 cells. The fluorescence properties of compounds II 1 , II 6 , II 11 , II 16 , II 23 , II 28 , and II 35 were also studied and compound II 28 afforded the highest photoluminescence quantum yield (38%).

  一系列新型2H-吡唑[4,3-c]六氢吡啶衍生物（II）已被设计和合成。目标化合物通过元素分析和光谱（1H NMR、IR和MS）数据得到确认，化合物（II 1）的绝对构型通过单晶X射线衍射法得以确认。对目标化合物在体外针对两个人乳腺癌细胞株MCF-7和MDA-MB-231进行了MTT法评估其细胞毒性。大多数化合物表现出良好的抑制作用，其中化合物II 21（对MCF-7的IC50为4.7 μM，對MDA-MB-231的IC50为9.3 μM）、II 33（对MCF-7的IC50为2.4 μM，對MDA-MB-231的IC50为4.2 μM）和II 40（对MCF-7的IC50为3.3 μM，對MDA-MB-231的IC50为8.6 μM）显示出比5-氟尿嘧啶（对MCF-7的IC50为4.8 μM，對MDA-MB-231的IC50为9.6 μM）更好的抑制活性。流式细胞仪分析和DNA片段化结果表明，II 33具有细胞毒性，并能诱导MCF-7细胞的凋亡。还研究了化合物II 1、II 6、II 11、II 16、II 23、II 28和II 35的荧光特性，其中化合物II 28的光致发光量子产率最高（38%）。