1-[4,4'']Bipiperidinyl-1-yl-heptadecan-1-one; hydrochloride | 867059-77-6

• 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-[4,4'']Bipiperidinyl-1-yl-heptadecan-1-one; hydrochloride
• 英文别名: 1-(4-piperidin-4-ylpiperidin-1-yl)heptadecan-1-one
• CAS: 867059-77-6
• 化学式: C₂₇H₅₂N₂O
• 分子量: 420.723
• InChiKey: IYDCUSISQWLHLJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.7
• 重原子数：
  30
• 可旋转键数：
  16
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.96
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-[4,4'']Bipiperidinyl-1-yl-heptadecan-1-one; hydrochloride 、 聚合甲醛 在 甲酸 作用下， 以 乙醇 为溶剂， 反应 4.0h， 生成 1-(1''-Methyl-[4,4'']bipiperidinyl-1-yl)-heptadecan-1-one; hydrochloride
  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
• 作为产物：
  描述：

  N-boc-4,4-联哌啶 在 盐酸 、 三乙胺 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 生成 1-[4,4'']Bipiperidinyl-1-yl-heptadecan-1-one; hydrochloride
  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

• 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.