Tert-butyl 4-(2-anilino-2-oxoethyl)piperazine-1-carboxylate | 1325635-58-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: Tert-butyl 4-(2-anilino-2-oxoethyl)piperazine-1-carboxylate
• CAS: 1325635-58-2
• 化学式: C₁₇H₂₅N₃O₃
• mdl: MFCD17869634
• 分子量: 319.404
• InChiKey: OKKYWSAWQUDKKY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.529
• 拓扑面积：
  61.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Tert-butyl 4-(2-anilino-2-oxoethyl)piperazine-1-carboxylate 在 盐酸 、 盐酸羟胺 、 potassium hydrogencarbonate 、 sodium hydroxide 作用下， 以 甲醇 、 乙醇 、 水 、 乙腈 为溶剂， 反应 16.0h， 生成 N-hydroxy-3-(4-phenylcarbamoylmethylpiperazin-1-yl)propionamide
  参考文献：
  名称：

  Design, Synthesis and Biological Evaluation of Hydroxamic Acid Derivatives as Potential High Density Lipoprotein (HDL) Receptor CLA-1 Up-Regulating Agents

  摘要：

  在我们最近的出版物中报道，三氟氯乙酰胺（TSA）和水杨酰胺羟肟酸（SAHA）被发现是新型的人类高密度脂蛋白（HDL）受体CD36和溶酶体整合膜蛋白-II类似物1（CLA-1）的上调剂。作为更全面探索CLA-1上调剂结构-活性关系（SAR）的一部分，我们合成了一系列羟肟酸衍生物，并在HepG2细胞中评估了它们的CLA-1上调活性。某些化合物在10 μg/mL浓度下表现出超过10倍的CLA-1表达上调。化合物1g展现出最佳效力，其EC50低于TSA（EC50 = 0.32 μM对比1.2 μM）。这些化合物提供了早期的新CLA-1上调剂，具有治疗动脉粥样硬化的潜力。

  DOI：

  10.3390/molecules16119178
• 作为产物：
  描述：

  苯胺 在 potassium hydrogencarbonate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 生成 Tert-butyl 4-(2-anilino-2-oxoethyl)piperazine-1-carboxylate
  参考文献：
  名称：

  Design, Synthesis and Biological Evaluation of Hydroxamic Acid Derivatives as Potential High Density Lipoprotein (HDL) Receptor CLA-1 Up-Regulating Agents

  摘要：

  在我们最近的出版物中报道，三氟氯乙酰胺（TSA）和水杨酰胺羟肟酸（SAHA）被发现是新型的人类高密度脂蛋白（HDL）受体CD36和溶酶体整合膜蛋白-II类似物1（CLA-1）的上调剂。作为更全面探索CLA-1上调剂结构-活性关系（SAR）的一部分，我们合成了一系列羟肟酸衍生物，并在HepG2细胞中评估了它们的CLA-1上调活性。某些化合物在10 μg/mL浓度下表现出超过10倍的CLA-1表达上调。化合物1g展现出最佳效力，其EC50低于TSA（EC50 = 0.32 μM对比1.2 μM）。这些化合物提供了早期的新CLA-1上调剂，具有治疗动脉粥样硬化的潜力。

  DOI：

  10.3390/molecules16119178

文献信息

• Design, Synthesis, and Structure–Activity Relationship Studies of Novel Indolyalkylpiperazine Derivatives as Selective 5-HT_1A Receptor Agonists
  作者：Wenli Wang、Lan Zheng、Wei Li、Chen Zhu、Weiqing Peng、Bing Han、Wei Fu

  DOI：10.1021/acs.jcim.9b00926

  日期：2020.1.27

  5-HT1A receptor (5-HT1AR) agonists have been implicated in the treatment of a variety of central nervous system (CNS) diseases such as depression and anxiety, et al. Based on our previously found compound FW01 (Ki = 51 ± 16 nM) obtained by virtual screening, a series of FW01 derivatives were designed and synthesized by the modification of the amide tail group as well as indole headgroup of FW01. SAR

  5-HT1A受体（5-HT1AR）激动剂已涉及多种中枢神经系统（CNS）疾病的治疗，例如抑郁症和焦虑症等。基于我们先前发现的通过虚拟筛选获得的化合物FW01（Ki = 51±16 nM），通过修饰FW01的酰胺尾基和吲哚基团设计并合成了一系列FW01衍生物。SAR探索发现，酰胺尾基和吲哚基团在确定对多巴胺和5-羟色胺受体亚型的结合亲和力和选择性中起着关键作用。在所有测试的化合物中，9_24的Ki值为5±0.6 nM，对5-HT1AR的选择性很好。[35S]GTPγS分析显示9_24是对5-HT1AR的完全激动剂，EC50值为0.059 nM，显示为266.2和146。对5-HT2A和D3的选择性是4倍。用5-HT1AR-9_24进行了分子动力学模拟和分子对接研究，以揭示其高活性和选择性的机理。最后，提出了5-HT1AR的逐步9_24诱导信号转导机制。
• The Design and Synthesis of 1,4-Substituted Piperazine Derivatives as Triple Reuptake Inhibitors
  作者：Min-Soo Han、Young-Hue Han、Chi-Man Song、Hoh-Gyu Hahn

  DOI：10.5012/bkcs.2012.33.8.2597

  日期：2012.8.20

  Novel 1,4-substituted piperazine derivatives 5, Series A and B were designed by fragment analysis and molecular modification of 4 selected piperazine-containing compounds which possess antidepressant activity. We synthesized new 39 analogues of Series A and 10 compounds of Series B, respectively. The antidepressant screening against DA, NE, and serotonin neurotransmitter uptake inhibition was carried

  通过对 4 种选定的具有抗抑郁活性的含哌嗪化合物进行片段分析和分子修饰，设计了新型 1,4-取代的哌嗪衍生物 5、A 和 B 系列。我们分别合成了 A 系列的 39 种新类似物和 B 系列的 10 种化合物。使用 Neurotransmitter Transporter Uptake Assay Kit 进行针对 DA、NE 和 5-羟色胺神经递质摄取抑制的抗抑郁药筛选。系列 B 中的化合物对 SERT、NET 和 DAT 的再摄取抑制活性比系列 A 中的更高。系列 B 中哌嗪中心中心和末端苯环之间的间隔物长度似乎发挥了作用。活动中的重要作用。
• CARBAMATE COMPOUNDS AND OF MAKING AND USING SAME
  申请人：Abide Therapeutics, Inc.

  公开号：US20150080364A1

  公开（公告）日：2015-03-19

  Provided herein are carbamate compounds which may be useful in the treatment of for example, pain, solid tumors and/or obesity.

  本文提供了一些氨基甲酸酯化合物，可能对例如疼痛、实体肿瘤和/或肥胖症的治疗有用。
• Design, Synthesis, and Evaluation of Indolebutylamines as a Novel Class of Selective Dopamine D3 Receptor Ligands
  作者：Peng Du、Lili Xu、Jiye Huang、Kunqian Yu、Rui Zhao、Bo Gao、Hualiang Jiang、Weili Zhao、Xuechu Zhen、Wei Fu

  DOI：10.1111/cbdd.12158

  日期：2013.9

  A series of indolebutylamine derivatives were designed, synthesized, and evaluated as a novel class of selective ligands for the dopamine 3 receptor. The most potent compound 11q binds to dopamine 3 receptor with a Ki value of 124 nm and displays excellent selectivity over the dopamine 1 receptor and dopamine 2 receptor. Investigation based on structural information indicates that site S182 located in extracellular loop 2 may account for high selectivity of compounds. Interaction models of the dopamine 3 receptor‐11q complex and structure‐activity relationships were discussed by integrating all available experimental and computational data with the eventual aim to discover potent and selective ligands to dopamine 3 receptor.
• Higher-Affinity Agonists of 5-HT_1AR Discovered through Tuning the Binding-Site Flexibility
  作者：Peng Lian、LinLang Li、Chuanrong Geng、Xuechu Zhen、Wei Fu

  DOI：10.1021/acs.jcim.5b00164

  日期：2015.8.24

  Discovery of high-affinity and high-selectivity agonists of 5-HT1AR. has become very attractive due to their potential therapeutic effects on multiple 5-HT1AR-related psychological and neurological problems. On the basis of our previously designed lead compound FW01 (K-i = 51.9 nM, denoted as 9a in the present study), we performed large-scale molecular dynamics simulations and molecular docking operations on 5-HT1AR-9a binding. We found the flip-packing events for the headgroup of 9a, and we also found that its tail group could bind flexibly at the agornst-binding site of 5-HT1AR. By finely tuning the flip-packing phenomenon of the 9a headgroup and tuning the binding flexibility of 9a tail group, we virtually designed a series of new 9a derivatives through molecular docking operations and first-principles calculations and predicted that these newly designed 9a derivatives should be higher-affinity agonists of 5-HT1AR. The computational predictions on the new 9a derivatives have been confirmed by our wet-experimental studies as chemical synthesis, binding affinity assays, and agonistic-function assays. The consistency between our computational design and wet-experimental measurements has led to our discovery of higher-affinity agonists of 5-HT1AR, with,similar to 50-fold increase in receptor-binding affinity and similar to 25-fold improvements in agonistic function. In addition, our newly designed 5-HT1AR agonists showed very high selectivity of 5-HT1AR over subtype 5-HT2AR and also over three subtypes of dopamine receptors (D-1, D-2, and D-3).