1-(4-(3-(piperidin-1-yl)propoxy)benzyl)piperidin-4-carboxylic acid | 1609110-31-7

• 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-carboxylic acid
• 英文别名: 1-[[4-(3-Piperidin-1-ylpropoxy)phenyl]methyl]piperidine-4-carboxylic acid
• CAS: 1609110-31-7
• 化学式: C₂₁H₃₂N₂O₃
• 分子量: 360.497
• InChiKey: GMRWCGDPKMVQCK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  53
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(4-(3-(piperidin-1-yl)propoxy)benzyl)piperidin-4-carboxylic acid 、 炔丙胺 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以54%的产率得到1-(4-(3-(piperidin-1-yl)propoxy)benzyl)-N-(prop-2-ynyl)piperidine-4-carboxamide
  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：

  对羟基苯甲醛 在 水 、 三乙酰氧基硼氢化钠 、 potassium carbonate 、 potassium iodide 作用下， 以 四氢呋喃 、 乙醇 、 1,2-二氯乙烷 、 丙酮 为溶剂， 反应 53.0h， 生成 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

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.