4-pentadecylaminopiperidine

• 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-pentadecylaminopiperidine
• 英文别名: pentadecylpiperidin-4-ylamine；BC5；Pentadecyl-piperidin-4-yl-amine; dihydrochloride；N-pentadecylpiperidin-4-amine
• 化学式: C₂₀H₄₂N₂
• 分子量: 310.567
• InChiKey: OSDLUOXSOGOQIN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 重原子数：
  22
• 可旋转键数：
  15
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  24.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-pentadecylaminopiperidine 、 2-溴乙胺氢溴酸盐 在 potassium carbonate 作用下， 以 氯仿 为溶剂， 反应 8.0h， 以40%的产率得到N-[1-(2-aminoethyl)piperidin-4-yl]-N-pentadecylamine
  参考文献：
  名称：

  [35S]GTPγS binding studies of amphiphilic drugs-activated Gi proteins: A caveat

  摘要：

  This paper documents a serious problem met during the testing of Gi protein-activating properties of a new series of synthetic compounds by measuring the induced binding of [(35)S]GTP gamma S to different subtypes of Gi protein. The problem arose from the strong affinity between [(35)S]GTP gamma S and the tested compounds, that are characterized by several (2-4) positive charges and high lipophilicity. Apparently, such affinity yields insoluble, labelled complexes that, also in the absence of Gi protein, are retained on the filters and give rise to false positive results. (c) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.02.097
• 作为产物：
  描述：

  溴代十五烷 在 palladium on activated charcoal 氢气 、 三乙胺 作用下， 以 乙醇 、 乙腈 为溶剂， 20.0 ℃ 、365.42 kPa 条件下， 反应 27.0h， 生成 4-pentadecylaminopiperidine
  参考文献：
  名称：

  Design, Synthesis, and Preliminary Pharmacological Evaluation of a Set of Small Molecules That Directly Activate Gi Proteins

  摘要：

  Heterotrimeric G proteins play a pivotal role in the communication of cells with the environment. G proteins are stimulated by cell surface receptors (GPCR) that catalyze the exchange of GDP, bound to G alpha subunit, with GTP and can per se be the target of drugs. Based on the structure of two nonpeptidic modulators of Gi proteins, a series of new molecules characterized by a long hydrophobic chain and at least two nitrogen atoms protonated at physiological pH was designed. The compounds were tested for their ability to stimulate binding of GTP gamma S to recombinant Gi proteins. Gi activation properties were also evaluated by inhibition of adenylyl cyclase activity in intact lymphocytes. Most compounds were able to stimulate GTP gamma S binding and to inhibit cAMP production at micromolar doses. Among the active compounds, 34 showed good efficacy and was the most potent compound studied, particularly on alpha(0) subtype; its regioisomer, 36, was the most efficacious one. Compound 7 showed also an interesting profile as it showed selectivity toward the alpha(0) subtype, in both efficacy and potency. Some of the compounds synthesized and found to be active may be useful leads to develop more potent and selective Gi protein modulators.

  DOI：

  10.1021/jm050498l

文献信息

• [35S]GTPγS binding studies of amphiphilic drugs-activated Gi proteins: A caveat
  作者：Dina Manetti、Lorenzo Di Cesare Mannelli、Silvia Dei、Luca Guandalini、Elisabetta Martini、Martina Banchelli、Carla Ghelardini

  DOI：10.1016/j.bmcl.2009.02.097

  日期：2009.4

  This paper documents a serious problem met during the testing of Gi protein-activating properties of a new series of synthetic compounds by measuring the induced binding of [(35)S]GTP gamma S to different subtypes of Gi protein. The problem arose from the strong affinity between [(35)S]GTP gamma S and the tested compounds, that are characterized by several (2-4) positive charges and high lipophilicity. Apparently, such affinity yields insoluble, labelled complexes that, also in the absence of Gi protein, are retained on the filters and give rise to false positive results. (c) 2009 Elsevier Ltd. All rights reserved.
• Design, Synthesis, and Preliminary Pharmacological Evaluation of a Set of Small Molecules That Directly Activate Gi Proteins
  作者：Dina Manetti、Lorenzo Di Cesare Mannelli、Silvia Dei、Nicoletta Galeotti、Carla Ghelardini、Maria Novella Romanelli、Serena Scapecchi、Elisabetta Teodori、Alessandra Pacini、Alessandro Bartolini、Fulvio Gualtieri

  DOI：10.1021/jm050498l

  日期：2005.10.1

  Heterotrimeric G proteins play a pivotal role in the communication of cells with the environment. G proteins are stimulated by cell surface receptors (GPCR) that catalyze the exchange of GDP, bound to G alpha subunit, with GTP and can per se be the target of drugs. Based on the structure of two nonpeptidic modulators of Gi proteins, a series of new molecules characterized by a long hydrophobic chain and at least two nitrogen atoms protonated at physiological pH was designed. The compounds were tested for their ability to stimulate binding of GTP gamma S to recombinant Gi proteins. Gi activation properties were also evaluated by inhibition of adenylyl cyclase activity in intact lymphocytes. Most compounds were able to stimulate GTP gamma S binding and to inhibit cAMP production at micromolar doses. Among the active compounds, 34 showed good efficacy and was the most potent compound studied, particularly on alpha(0) subtype; its regioisomer, 36, was the most efficacious one. Compound 7 showed also an interesting profile as it showed selectivity toward the alpha(0) subtype, in both efficacy and potency. Some of the compounds synthesized and found to be active may be useful leads to develop more potent and selective Gi protein modulators.