(4-(3-(piperidin-1-yl)propoxy)phenyl)methanol | 464898-19-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (4-(3-(piperidin-1-yl)propoxy)phenyl)methanol
• 英文别名: 1-[3-(4-Hydroxymethylphenoxy)propyl]piperidine；[4-(3-piperidin-1-ylpropoxy)phenyl]methanol
• CAS: 464898-19-9
• 化学式: C₁₅H₂₃NO₂
• 分子量: 249.353
• InChiKey: VPESFDVGWJMCNH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  32.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (4-(3-(piperidin-1-yl)propoxy)phenyl)methanol 在 氯化亚砜 、 potassium carbonate 、 potassium iodide 作用下， 以 丙酮 、 甲苯 为溶剂， 反应 51.0h， 生成 3-benzoyl-1-(4-(3-(piperidin-1-yl)propoxy)benzyl)pyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  Studies on molecular properties prediction and histamine H3 receptor affinities of novel ligands with uracil-based motifs

  摘要：

  The histamine H-3 receptor (H3R) plays a role in cognitive and memory processes and is involved in different neurological disorders, including Alzheimer's disease, schizophrenia, and narcolepsy. Therefore, several hH(3)R antagonists/inverse agonists entered clinical phases for a broad spectrum of mainly centrally occurring diseases. However, many other promising candidates failed due to their pharmacokinetic profile, mostly because of their strong lipophilicity accompanied with low solubility. Analysis of previous potential H3R selective antagonists/inverse agonists, e.g. pitolisant, revealed promising results concerning physicochemical properties and drug-likeness. Herein, a series of new hH(3)R ligands 8-20 consisting of piperidin-1-yl or piperidin-1-yl-propoxyphenyl coupled to different uracil, thymine, and 5,6-dimethyluracil related moieties, were synthesized, evaluated on their binding properties at the hH(3)R and the estimation of different physicochemical and drug-likeness properties. Due to the coupling to various positions at pyrimidine-2,4-(1H,3H)-dione, affinity at hH(3)Rs and drug-likeness parameters have been improved. For instance, compound 9 showed in addition to high affinity at the hH(3)R (pK(i) (hH(3)R) = 8.14) clog S, clog P, LE, LipE, and drug-likeness score values of -4.36, 3.47, 0.34, 4.63, and 1.54, respectively. Also, the methyl substituted analog 17 (pK(i); (hH(3)R) = 8.15) revealed LE, LipE and drug-likeness score values of -3.29, 2.47, 0.49, 5.52, and 1.76, respectively. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.09.011
• 作为产物：
  描述：

  1-哌啶丙醇 在 氯化亚砜 、 potassium carbonate 、 potassium iodide 作用下， 以 丙酮 、 甲苯 为溶剂， 反应 3.0h， 生成 (4-(3-(piperidin-1-yl)propoxy)phenyl)methanol
  参考文献：
  名称：

  Studies on molecular properties prediction and histamine H3 receptor affinities of novel ligands with uracil-based motifs

  摘要：

  The histamine H-3 receptor (H3R) plays a role in cognitive and memory processes and is involved in different neurological disorders, including Alzheimer's disease, schizophrenia, and narcolepsy. Therefore, several hH(3)R antagonists/inverse agonists entered clinical phases for a broad spectrum of mainly centrally occurring diseases. However, many other promising candidates failed due to their pharmacokinetic profile, mostly because of their strong lipophilicity accompanied with low solubility. Analysis of previous potential H3R selective antagonists/inverse agonists, e.g. pitolisant, revealed promising results concerning physicochemical properties and drug-likeness. Herein, a series of new hH(3)R ligands 8-20 consisting of piperidin-1-yl or piperidin-1-yl-propoxyphenyl coupled to different uracil, thymine, and 5,6-dimethyluracil related moieties, were synthesized, evaluated on their binding properties at the hH(3)R and the estimation of different physicochemical and drug-likeness properties. Due to the coupling to various positions at pyrimidine-2,4-(1H,3H)-dione, affinity at hH(3)Rs and drug-likeness parameters have been improved. For instance, compound 9 showed in addition to high affinity at the hH(3)R (pK(i) (hH(3)R) = 8.14) clog S, clog P, LE, LipE, and drug-likeness score values of -4.36, 3.47, 0.34, 4.63, and 1.54, respectively. Also, the methyl substituted analog 17 (pK(i); (hH(3)R) = 8.15) revealed LE, LipE and drug-likeness score values of -3.29, 2.47, 0.49, 5.52, and 1.76, respectively. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.09.011

文献信息

• Histamine H3 receptor antagonists with peptidomimetic (keto)piperazine structures to inhibit Aβ oligomerisation
  作者：Markus Falkenstein、David Reiner-Link、Aleksandra Zivkovic、Ian Gering、Dieter Willbold、Holger Stark

  DOI：10.1016/j.bmc.2021.116462

  日期：2021.11

  build toxic oligomers. Design of disease modifying multi target directed ligand (MTDL) has been performed, which disable PPI on the one hand and on the other hand, act as procognitive antagonists at the histamine H3 receptor (H3R). The synthetized compounds are structurally based on peptidomimetic amino acid-like structures mainly as keto, diketo-, or acyl variations of a piperazine moiety connected to

  阿尔茨海默病 (AD) 是最突出的神经退行性疾病，具有很高的医疗需求。蛋白质-蛋白质-相互作用 (PPI) 相互作用在 AD 中具有关键作用，其中 β-淀粉样蛋白结构 (Aβ) 构建有毒低聚物。已经进行了疾病修饰多靶点定向配体 (MTDL) 的设计，其一方面禁用 PPI，另一方面作为组胺 H 3受体 (H 3 R) 的促认知拮抗剂。合成的化合物在结构上基于肽模拟氨基酸样结构，主要是与 H 3 R 药效团连接的哌嗪部分的酮基、二酮基或酰基变体。它们中的大多数在 H 3处表现出低纳摩尔亲和力R 和一些对 Aβ-单体具有良好亲和力的物质。所描述的结构-活性关系 (SAR) 为 MTDL 提供了新的可能性，其优化的配置文件结合了 AD 中的症状和潜在因果治疗方法。
• Kojic Acid Derivatives as Histamine H3 Receptor Ligands
  作者：Kerstin Sander、Tim Kottke、Lilia Weizel、Holger Stark

  DOI：10.1248/cpb.58.1353

  日期：——

  surface area (tPSA)) and hence, potentially modifies the pharmacokinetic profile of the different derivatives. Benzyl-1-(4-(3-(piperidin-1-yl)propoxy)phenyl)methanamine ligands 3 and 4 belong to the centrally acting diamine-based class of H(3)R antagonist/inverse agonist, whereas kojic acid analogues 6 and 7 might act peripherally. The latter compounds state promising lead structures in the development

  组胺H（3）受体（H（3）R）是用于治疗主要集中发生的疾病的新化合物的开发中有希望的目标。但是，已经出现了新兴的新型治疗概念，H（3）R领域的某些适应症（例如偏头痛，疼痛或过敏性鼻炎）可能会利用外周作用的配体。在这项工作中，曲酸衍生的结构元​​件被插入到一个完善的H（3）R拮抗剂/反向激动剂支架中，以研究γ-吡喃酮相对于H（3）R药效基团的不同部分的生物等效甾体潜力。最亲和的化合物在低纳摩尔浓度范围内显示受体结合。含曲酸的配体及其相应的苯基类似物（3-7）的评估和比较表明，新整合的支架极大地影响了化学性质（S Log P，拓扑极性表面积（tPSA）），因此可能会改变药代动力学特征不同的衍生品。苄基-1-（4-（3-（3-哌啶基-1-基）丙氧基）苯基）甲胺配体3和4属于H（3）R拮抗剂/反向激动剂的基于中枢作用的二胺类，而曲酸类似物6和7可能在外围起作用。后者的化合物在H（3）R配体的发展过
• NOVEL HISTAMINE H3-RECEPTOR LIGANDS AND THEIR THERAPEUTIC APPLICATIONS
  申请人：Bertrand Isabelle

  公开号：US20090111808A1

  公开（公告）日：2009-04-30

  The present patent application concerns compounds of formula (I) with R1 and R2 taken together with the nitrogen atom to which they are attached, form a mono or bicyclic saturated nitrogen-containing ring; their preparation and their use as a H3 receptor ligand for treating e.g. CNS disorders like Alzheimer's disease.

  本专利申请涉及式(I)的化合物，其中R1和R2与它们所连接的氮原子结合形成单环或双环饱和含氮环; 它们的制备及其用作H3受体配体，用于治疗例如阿尔茨海默病等中枢神经系统疾病。
• Histamine H3-receptor ligands and their therapeutic applications
  申请人：Bioprojet

  公开号：US08076329B2

  公开（公告）日：2011-12-13

  The present patent application concerns compounds of formula (I) with R1 and R2 taken together with the nitrogen atom to which they are attached, form a mono or bicyclic saturated nitrogen-containing ring; their preparation and their use as a H3 receptor ligand for treating e.g. CNS disorders like Alzheimer's disease.

  本专利申请涉及公式（I）化合物，其中R1和R2与它们附着的氮原子一起形成单环或双环饱和含氮环；它们的制备以及它们作为H3受体配体用于治疗例如阿尔茨海默病等中枢神经系统疾病。
• First Metal-Containing Histamine H₃ Receptor Ligands
  作者：Kerstin Sander、Tim Kottke、Claas Hoffend、Miriam Walter、Lilia Weizel、Jean-Claude Camelin、Xavier Ligneau、Erich H. Schneider、Roland Seifert、Jean-Charles Schwartz、Holger Stark

  DOI：10.1021/ol100419y

  日期：2010.6.4

  Iron-containing ligands targeting the human histamine H-3 receptor (hH(3)R) were prepared. The compounds contain ferrocene sandwich complexes coupled via different linkers to a basic hH(3)R antagonist/inverse agonist pharmacophore. In a click chemistry approach, a triazole was successfully inserted as a new linking element. Two ferrocenylmethylamines and a ferrocenyltriazole were the most affine hH(3)R ligands within this series, showing receptor binding in the nano- and subnanomolar concentration range.