4-cyclohexyl-4-hydroxy-1-benzylpiperidine | 1189396-28-8

• 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: 4-cyclohexyl-4-hydroxy-1-benzylpiperidine
• 英文别名: 1-Benzyl-4-cyclohexylpiperidin-4-ol
• CAS: 1189396-28-8
• 化学式: C₁₈H₂₇NO
• 分子量: 273.418
• InChiKey: CSEMSXLNWLKMJG-UHFFFAOYSA-N

物化性质

• 沸点：
  407.1±25.0 °C(Predicted)
• 密度：
  1.087±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  23.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-cyclohexyl-4-hydroxy-1-benzylpiperidine 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 为溶剂， 反应 96.0h， 以92%的产率得到4-cyclohexyl-4-piperidinol
  参考文献：
  名称：

  Exploring the Importance of Piperazine N-Atoms for σ₂ Receptor Affinity and Activity in a Series of Analogs of 1-Cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine (PB28)

  摘要：

  sigma(2)-Agonist 1-cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine (7, PB 28), which proved to revert doxorubicin resistance in breast cancer cells, was taken as a template to prepare new analogs. One of the two basic N-atoms wits alternatively replaced by it methine or converted into an amide or ammonium function, with the aim of finding out which of them was essential For sigma(2) receptor affinity and activity. Some simply 4-substituted 1-cyclohexylpiperazines were also investigated. None of the compounds was as high-affinity as 7 (sigma K-2(i) = 0.68, sigma K-1(i) = 0.38 nM), proving that both basic N-atoms ensure better sigma(2) receptor binding. Amide 36 emerged as high-affinity (K-i = 0.11 nM) and noteworthy selective (1627-fold) or, ligand. Small N-cyclohexylpiperazine 59 displayed the highest sigma(2) affinity (K-i = 4.70 nM). The sigma(2)/sigma(1) selectivities were generally low. Antiproliferative assay in SK-N-SH cells revealed piperidines 24 and 15 as putative sigma(2), agonists (EC(50)s 1.40 and 3.64 mu M respectively) more potent than 7.

  DOI：

  10.1021/jm9007505
• 作为产物：
  描述：

  溴代环己烷 、 N-苄基哌啶酮 在 magnesium 作用下， 以 四氢呋喃 为溶剂， 以30%的产率得到4-cyclohexyl-4-hydroxy-1-benzylpiperidine
  参考文献：
  名称：

  Exploring the Importance of Piperazine N-Atoms for σ₂ Receptor Affinity and Activity in a Series of Analogs of 1-Cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine (PB28)

  摘要：

  sigma(2)-Agonist 1-cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine (7, PB 28), which proved to revert doxorubicin resistance in breast cancer cells, was taken as a template to prepare new analogs. One of the two basic N-atoms wits alternatively replaced by it methine or converted into an amide or ammonium function, with the aim of finding out which of them was essential For sigma(2) receptor affinity and activity. Some simply 4-substituted 1-cyclohexylpiperazines were also investigated. None of the compounds was as high-affinity as 7 (sigma K-2(i) = 0.68, sigma K-1(i) = 0.38 nM), proving that both basic N-atoms ensure better sigma(2) receptor binding. Amide 36 emerged as high-affinity (K-i = 0.11 nM) and noteworthy selective (1627-fold) or, ligand. Small N-cyclohexylpiperazine 59 displayed the highest sigma(2) affinity (K-i = 4.70 nM). The sigma(2)/sigma(1) selectivities were generally low. Antiproliferative assay in SK-N-SH cells revealed piperidines 24 and 15 as putative sigma(2), agonists (EC(50)s 1.40 and 3.64 mu M respectively) more potent than 7.

  DOI：

  10.1021/jm9007505

文献信息

• Design and optimization of quinazoline derivatives as melanin concentrating hormone receptor 1 (MCHR1) antagonists
  作者：Sanjita Sasmal、Gade Balaji、Hariprasada R. Kanna Reddy、D. Balasubrahmanyam、Gujjary Srinivas、ShivaKumar Kyasa、Pradip K. Sasmal、Ish Khanna、Rashmi Talwar、J. Suresh、Vikram P. Jadhav、Syed Muzeeb、Dhanya Shashikumar、K. Harinder Reddy、V.J. Sebastian、Thomas M. Frimurer、Øystein Rist、Lisbeth Elster、Thomas Högberg

  DOI：10.1016/j.bmcl.2012.03.050

  日期：2012.5

  mediator of energy homeostasis and plays a role in metabolic and CNS disorders. The modeling-supported design, synthesis and multi-parameter optimization (biological activity, solubility, metabolic stability, hERG) of novel quinazoline derivatives as MCHR1 antagonists are described. The in vivo proof of principle for weight loss with a lead compound from this series is exemplified. Clusters of refined hMCHR1

  黑色素浓缩激素（MCH）是能量稳态的重要介质，在代谢和中枢神经系统疾病中发挥作用。描述了作为 MCHR1 拮抗剂的新型喹唑啉衍生物的模型支持设计、合成和多参数优化（生物活性、溶解度、代谢稳定性、hERG）。举例说明了该系列先导化合物减肥原理的体内证明。开发了源自​​ β2-肾上腺素能受体 X 射线结构（包括细胞外环）的精制 hMCHR1 同源模型簇，并用于指导设计。
• GLP-1 RECEPTOR MODULATORS
  申请人：Celgene International II Sarl

  公开号：EP3230276B1

  公开（公告）日：2020-09-02