(1-(4-(3-(哌啶-1-基)丙氧基)苄基)哌啶-4-基)甲醇 | 1028458-62-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: (1-(4-(3-(哌啶-1-基)丙氧基)苄基)哌啶-4-基)甲醇
• 英文名称: (1-(4-(3-(piperidin-1-yl)propoxy)benzyl)piperidin-4-yl)methanol
• 英文别名: [1-[[4-(3-Piperidin-1-ylpropoxy)phenyl]methyl]piperidin-4-yl]methanol
• CAS: 1028458-62-9
• 化学式: C₂₁H₃₄N₂O₂
• 分子量: 346.513
• InChiKey: CEVWULHGGQMGPD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  25
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  35.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  对羟基苯甲醛 在 三乙酰氧基硼氢化钠 、 potassium carbonate 、 potassium iodide 作用下， 以 1,2-二氯乙烷 、 丙酮 为溶剂， 反应 60.0h， 生成 (1-(4-(3-(哌啶-1-基)丙氧基)苄基)哌啶-4-基)甲醇
  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

文献信息

• Lead identification of acetylcholinesterase inhibitors–histamine H3 receptor antagonists from molecular modeling
  作者：Scott D. Bembenek、John M. Keith、Michael A. Letavic、Richard Apodaca、Ann J. Barbier、Lisa Dvorak、Leah Aluisio、Kirsten L. Miller、Timothy W. Lovenberg、Nicholas I. Carruthers

  DOI：10.1016/j.bmc.2007.12.048

  日期：2008.3.15

  histamine H(3) receptor antagonist. Both histamine H(3) receptor antagonists and AChE inhibitors improve and augment cholinergic neurotransmission in the cortex. However, whereas an AChE inhibitor will impart its effect everywhere, a histamine H(3) antagonist will raise acetylcholine levels mostly in the brain as its mode of action will primarily be on the central nervous system. Therefore, the combination

  当前，对阿尔茨海默氏病（AD）的唯一临床有效治疗方法是使用乙酰胆碱酯酶（AChE）抑制剂。这些抑制剂的效力有限，因为它们仅治疗症状而不治疗疾病本身。另外，它们经常具有令人不快的副作用。在这里，我们考虑具有AChE抑制剂和组胺H（3）受体拮抗剂的作用的单个分子的生存力。组胺H（3）受体拮抗剂和AChE抑制剂均可改善和增强皮质中的胆碱能神经传递。但是，尽管AChE抑制剂将在各处发挥作用，但组胺H（3）拮抗剂将主要在大脑中提高乙酰胆碱水平，因为其作用方式主要在中枢神经系统上。所以，在单个分子中两种活性的组合可能是有利的。实际上，研究表明合适的双作用化合物可以提供所需的治疗效果，同时具有较少的不良副作用[CNS Drugs2004，18，827]。此外，最近的研究（2）表明AChE的外围阴离子位点（PAS）与β-淀粉样蛋白（betaA）肽相互作用。因此，能够破坏这种相互作用的分子可能对βA的产生或