tert-butyl 4-((4-fluorobenzyl)carbamoyl)piperidine-1-carboxylate | 327048-63-5

• 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: tert-butyl 4-((4-fluorobenzyl)carbamoyl)piperidine-1-carboxylate
• 英文别名: Tert-butyl 4-[(4-fluorobenzyl)carbamoyl]piperidine-1-carboxylate；tert-butyl 4-[(4-fluorophenyl)methylcarbamoyl]piperidine-1-carboxylate
• CAS: 327048-63-5
• 化学式: C₁₈H₂₅FN₂O₃
• 分子量: 336.407
• InChiKey: VLWOBYNGTPAMBB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-((4-fluorobenzyl)carbamoyl)piperidine-1-carboxylate 在 1-羟基苯并三唑 、 三乙胺 、 N,N-二异丙基乙胺 、 三氟乙酸 、 N,N'-二异丙基碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 13.0h， 生成 1-[4-[[(2-chloro-6-methylquinazolin-4-yl)amino]methyl]benzoyl]-N-(4-fluorobenzyl)piperidine-4-carboxamide
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of New Diaminoquinazolines as β-Catenin/Tcf4 Pathway Inhibitors

  摘要：

  More than 50 new diaminoquinazoline derivatives have been synthesized and evaluated in a colon carcinoma cell growth inhibition assay using HCT116 and SW480 cells. Twenty compounds with good cell growth inhibitory activities (<4 mu M) were tested as inhibitors of the beta-catenin/T cell transcription factor 4 (Tcf4) signaling pathway using a HCT116 cell-based luciferase reporter assay. Results from the biological activities as well as the comparative molecular field analysis (CoMFA) of the properties of the molecules yielded a preliminary structure-activity relationship (SAR). Three potent compounds, 74, 78, and 86, showed IC50 values <1 mu M for growth inhibition of HCT116 cells and similar to 1 mu M for SW480 cells, as well as IC50 values of 1.5-2.5 mu M for HCT116 cells with the luciferase reporter assay.

  DOI：

  10.1021/jm201494a
• 作为产物：
  描述：

  4-哌啶甲酸 在 sodium hydroxide 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 6.5h， 生成 tert-butyl 4-((4-fluorobenzyl)carbamoyl)piperidine-1-carboxylate
  参考文献：
  名称：

  具有固定药效基团构型的Ser42-Phe-Leu-Leu-Arg46基序序列的新型环状凝血酶受体衍生肽类似物的设计，合成和建模：Phe / Arg / NH2簇对于受体激活及其影响的重要性非肽凝血酶受体模拟物的设计。

  摘要：

  新颖的环状类似物环（Phe-Leu-Leu-Arg-epsilonLys-Dap）（1）和环（D-Phe-Leu-Leu-Arg-epsilonLys-Dap）（2），仅在根据最小的肽序列Phe-Leu-Leu-Arg设计和合成了Phe，该序列已发现对凝血酶受体具有生物活性。与其中Phe残基为D-构型的化合物2相比，其中所有氨基酸均具有L-构型的化合物1在大鼠主动脉松弛和大鼠纵向肌肉生物测定中表现出更高的活性。这归因于化合物1中Phe和Arg的空间接近性，而这在其非对映体化合物2中不存在，如NMR研究和计算分析的结合所描绘的。结构活性研究（SAR）表明，Phe和Arg侧链与伯氨基一起形成了一个主动识别基序，环状肽中存在另一个伯氨基会增强该识别基序。我们建议可比的环状构象可能是线性TRAP与凝血酶受体相互作用的原因。通过合成四种活性非肽凝血酶受体模拟物测试了该命题的有效性。发现了（S）-N-

  DOI：

  10.1021/jm0001525

文献信息

• 10.1007/s00044-024-03298-w
  作者：Du, Wen-Rong、Wei, Ben-Ben、Guo, Xin-Yuan、Lan, Yong、Shang, Pan-Pan、Wang, Yi-Xuan、Zhou, Xue-Wei、Wang, Xiao-Ke、Ma, Zheng-Yue

  DOI：10.1007/s00044-024-03298-w

  日期：——

  A series of 8-(piperazin-1-yl)imidazo[1,2-a]pyrazine derivatives were designed and synthesized as acetylcholinesterase inhibitors (AChEIs) and antioxidants for the treatment of Alzheimer’s disease (AD). Moreover, the biological evaluation results demonstrated that these synthesized compounds exhibited moderate inhibitory activities toward acetylcholinesterase (AChE) and radical scavenging activities

  设计并合成了一系列8-(哌嗪-1-基)咪唑并[ 1,2-a ]吡嗪衍生物作为乙酰胆碱酯酶抑制剂(AChEI)和抗氧化剂，用于治疗阿尔茨海默病(AD)。此外，生物学评价结果表明，这些合成的化合物对乙酰胆碱酯酶（AChE）具有中等的抑制活性和自由基清除活性。其中，化合物17r是最有效的AChE抑制剂，IC 50值为0.47 μM，对丁酰胆碱酯酶(BuChE)具有中等抑制活性(IC 50 = 11.02 μM)。 AChE相对于BuChE的选择性指数（SI）值为23.45，超过了参比药加兰他敏（AChE IC 50 = 5.01 μM，BuChE IC 50 = 18.46 μM，SI = 3.68）。化合物17o的抗氧化活性最好，IC 50值为89.33 μM，低于对照药物抗坏血酸（IC 50值=25.70 μM）。此外，分子对接研究结果表明， 17r可以同时结合AChE的催化活性位点和外周阴
• COMPOUNDS USEFUL IN THE TREATMENT OF INFLAMMATORY DISEASES
  申请人：GLAXO GROUP LIMITED

  公开号：EP1140837B1

  公开（公告）日：2004-08-18
• Design, synthesis, and biological evaluation of novel piperidine-4-carboxamide derivatives as potent CCR5 inhibitors
  作者：Suwen Hu、Quan Gu、Zhilong Wang、Zhiyong Weng、Yunrui Cai、Xiaowu Dong、Yongzhou Hu、Tao Liu、Xin Xie

  DOI：10.1016/j.ejmech.2013.11.013

  日期：2014.1

  Based on a putative 'Y shape' pharmacophore model of CCR5 inhibitors, a series of novel piperidine-4-carboxamide derivatives were designed and synthesized using a group-reverse strategy. Among synthesized target compounds, 16g (IC50 = 25.73 nM) and 16i (IC50 = 25.53 nM) showed equivalent inhibitory activity against CCR5 to that of the positive control maraviroc (IC50 = 25.43 nM) in calcium mobilization assay. Selected compounds were further tested for their antiviral activity in HIV-1 single cycle assay. Two compounds, 16g and 16i, displayed antiviral activity with IC50 values of 73.01 nM and 94.10 nM, respectively. Additionally, the pharmacokinetic properties and inhibitory potency against hERG of 16g were evaluated, providing a foundation for ongoing optimization. (C) 2013 Elsevier Masson SAS. All rights reserved.
• Amide Bond Formation with a New Fluorous Carbodiimide:  Separation by Reverse Fluorous Solid-Phase Extraction
  作者：Carlos del Pozo、Adam I. Keller、Tadamichi Nagashima、Dennis P. Curran

  DOI：10.1021/ol701631m

  日期：2007.10.1

  A new fluorous carbodiimide is introduced along with a convenient procedure for amide coupling reactions. Reactions of acids and amines under standard conditions for carbodiimide couplings, followed by simple reverse fluorous solid-phase extraction (FSPE) over standard silica gel, provide the target amide products in good yields and purities. The use of HFE-7100 as a fluorous solvent is crucial for the success of the reverse FSPE.
• Design, Synthesis, and Biological Evaluation of New Diaminoquinazolines as β-Catenin/Tcf4 Pathway Inhibitors
  作者：Yongjun Mao、Nan Lin、Wang Tian、Xiaofeng Han、Xiaobing Han、Ziwei Huang、Jing An

  DOI：10.1021/jm201494a

  日期：2012.2.9

  More than 50 new diaminoquinazoline derivatives have been synthesized and evaluated in a colon carcinoma cell growth inhibition assay using HCT116 and SW480 cells. Twenty compounds with good cell growth inhibitory activities (<4 mu M) were tested as inhibitors of the beta-catenin/T cell transcription factor 4 (Tcf4) signaling pathway using a HCT116 cell-based luciferase reporter assay. Results from the biological activities as well as the comparative molecular field analysis (CoMFA) of the properties of the molecules yielded a preliminary structure-activity relationship (SAR). Three potent compounds, 74, 78, and 86, showed IC50 values <1 mu M for growth inhibition of HCT116 cells and similar to 1 mu M for SW480 cells, as well as IC50 values of 1.5-2.5 mu M for HCT116 cells with the luciferase reporter assay.