ethyl 1-(4-(3-(piperidin-1-yl)propoxy)benzyl)piperidin-4-carboxylate | 1609110-27-1

• 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: ethyl 1-(4-(3-(piperidin-1-yl)propoxy)benzyl)piperidin-4-carboxylate
• 英文别名: ethyl 1-(4-(3-(piperidin-1-yl)propoxy)benzyl)piperidine-4-carboxylate；Ethyl 1-[[4-(3-piperidin-1-ylpropoxy)phenyl]methyl]piperidine-4-carboxylate；ethyl 1-[[4-(3-piperidin-1-ylpropoxy)phenyl]methyl]piperidine-4-carboxylate
• CAS: 1609110-27-1
• 化学式: C₂₃H₃₆N₂O₃
• 分子量: 388.55
• InChiKey: NHDREUSFAZYGFO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  28
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  42
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 1-(4-(3-(piperidin-1-yl)propoxy)benzyl)piperidin-4-carboxylate 在 水 、 potassium carbonate 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 以64%的产率得到1-(4-(3-(piperidin-1-yl)propoxy)benzyl)piperidin-4-carboxylic acid
  参考文献：
  名称：

  Benzylpiperidine variations on histamine H3 receptor ligands for improved drug-likeness

  摘要：

  Several hH(3)R antagonists/inverse agonists entered clinical phases for a broad spectrum of mainly centrally occurring diseases. Nevertheless, many promising candidates failed due to their pharmacokinetic profile, mostly because of their strong lipophilicity and their dibasic character. Analysis of previously, as potential PET ligands synthesized compounds (ST-889, ST-928) revealed promising results concerning physicochemical properties and drug-likeness. Herein, the synthesis, the evaluation of the binding properties at the hH3R and the estimation of different physicochemical and drug-likeness properties of further novel benzylpiperidine variations on H3R antagonists is described. Due to the introduction of various small hydrophilic moieties in the structure, drug-likeness parameters have been improved. For instance, compound 12 (ST-1032) showed in addition to high affinity at the H3R (pK(i) (hH(3)R) = 9.3) clogS, clogP, LE, LipE, and LELP values of -2.48, 2.18, 0.44, 7.14, and 4.95, respectively. Also, the keto derivative 5 (ST-1703, pKi (hH(3)R) = 8.6) revealed LipE and LELP values of 5.25 and 6.84, respectively. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.03.098
• 作为产物：
  描述：

  4-(3-氯丙氧基)苯甲醛 在 三乙酰氧基硼氢化钠 、 sodium carbonate 、 potassium iodide 作用下， 以 氯仿 、 乙腈 为溶剂， 反应 40.0h， 生成 ethyl 1-(4-(3-(piperidin-1-yl)propoxy)benzyl)piperidin-4-carboxylate
  参考文献：
  名称：

  多功能亚纳摩尔荧光配体使 NanoBRET 结合研究和组胺 H3 受体的单分子显微镜成为可能

  摘要：

  组胺 H 3受体 (H 3 R) 被认为是治疗各种神经系统疾病的有吸引力的药物靶点。我们在此报告了一种新型荧光 H 3 R 配体UR-NR266 的合成。广泛的药理学表征显示 UR-NR266 作为 H 3 R处的亚纳摩尔化合物，在组胺受体家族中具有特殊的选择性。所呈现的中性拮抗剂在动力学结合研究中显示出与其靶标的快速结合和完全解离。使用 UR-NR266 对 NanoBRET 竞争结合中标准 H 3 R 配体的详细表征突出了其作为分析未来 H 3的多功能药理学工具的价值R 配体。在所有实验中观察到的低非特异性结合也可以在 TIRF 和共聚焦显微镜中得到验证。这种荧光探针允许在各种分析中对天然 H 3 R 进行高度特异性分析，从光学高通量技术到生物物理分析和自然环境中的单分子研究。对 14 个受体的脱靶筛选显示 UR-NR266 是一种选择性化合物。

  DOI：

  10.1021/acs.jmedchem.1c01089

文献信息

• Benzylpiperidine variations on histamine H3 receptor ligands for improved drug-likeness
  作者：Kerstin Wingen、J. Stephan Schwed、Kathleen Isensee、Lilia Weizel、Aleksandra Živković、Dalibor Odazic、Holger Stark

  DOI：10.1016/j.bmcl.2014.03.098

  日期：2014.5

  Several hH(3)R antagonists/inverse agonists entered clinical phases for a broad spectrum of mainly centrally occurring diseases. Nevertheless, many promising candidates failed due to their pharmacokinetic profile, mostly because of their strong lipophilicity and their dibasic character. Analysis of previously, as potential PET ligands synthesized compounds (ST-889, ST-928) revealed promising results concerning physicochemical properties and drug-likeness. Herein, the synthesis, the evaluation of the binding properties at the hH3R and the estimation of different physicochemical and drug-likeness properties of further novel benzylpiperidine variations on H3R antagonists is described. Due to the introduction of various small hydrophilic moieties in the structure, drug-likeness parameters have been improved. For instance, compound 12 (ST-1032) showed in addition to high affinity at the H3R (pK(i) (hH(3)R) = 9.3) clogS, clogP, LE, LipE, and LELP values of -2.48, 2.18, 0.44, 7.14, and 4.95, respectively. Also, the keto derivative 5 (ST-1703, pKi (hH(3)R) = 8.6) revealed LipE and LELP values of 5.25 and 6.84, respectively. (C) 2014 Elsevier Ltd. All rights reserved.
• A Versatile Sub-Nanomolar Fluorescent Ligand Enables NanoBRET Binding Studies and Single-Molecule Microscopy at the Histamine H₃ Receptor
  作者：Niklas Rosier、Lukas Grätz、Hannes Schihada、Jan Möller、Ali Işbilir、Laura J. Humphrys、Martin Nagl、Ulla Seibel、Martin J. Lohse、Steffen Pockes

  DOI：10.1021/acs.jmedchem.1c01089

  日期：2021.8.12

  fluorescent H3R ligand. Broad pharmacological characterization revealed UR-NR266 as a sub-nanomolar compound at the H3R with an exceptional selectivity profile within the histamine receptor family. The presented neutral antagonist showed fast association to its target and complete dissociation in kinetic binding studies. Detailed characterization of standard H3R ligands in NanoBRET competition binding using

  组胺 H 3受体 (H 3 R) 被认为是治疗各种神经系统疾病的有吸引力的药物靶点。我们在此报告了一种新型荧光 H 3 R 配体UR-NR266 的合成。广泛的药理学表征显示 UR-NR266 作为 H 3 R处的亚纳摩尔化合物，在组胺受体家族中具有特殊的选择性。所呈现的中性拮抗剂在动力学结合研究中显示出与其靶标的快速结合和完全解离。使用 UR-NR266 对 NanoBRET 竞争结合中标准 H 3 R 配体的详细表征突出了其作为分析未来 H 3的多功能药理学工具的价值R 配体。在所有实验中观察到的低非特异性结合也可以在 TIRF 和共聚焦显微镜中得到验证。这种荧光探针允许在各种分析中对天然 H 3 R 进行高度特异性分析，从光学高通量技术到生物物理分析和自然环境中的单分子研究。对 14 个受体的脱靶筛选显示 UR-NR266 是一种选择性化合物。