1-(4-(3-(piperidin-1-yl)propoxy)benzyl)piperidin-4-one | 1609110-26-0

• 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: 1-(4-(3-(piperidin-1-yl)propoxy)benzyl)piperidin-4-one
• 英文别名: 1-[4-(3-Piperidin-1-yl-propoxy)-benzyl]-piperidin-4-one；1-[[4-(3-piperidin-1-ylpropoxy)phenyl]methyl]piperidin-4-one
• CAS: 1609110-26-0
• 化学式: C₂₀H₃₀N₂O₂
• 分子量: 330.47
• InChiKey: MWKQIJJXRDAVAB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  32.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (4-(3-(piperidin-1-yl)propoxy)phenyl)methanol hydrochloride 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 1-(4-(3-(piperidin-1-yl)propoxy)benzyl)piperidin-4-one
  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

• 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.