N-(5-((1,1-diethoxyethyl)ethoxyphosphoryl)pentyl)phthalimide | 200402-42-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: N-(5-((1,1-diethoxyethyl)ethoxyphosphoryl)pentyl)phthalimide
• 英文别名: 2-[5-[1,1-Diethoxyethyl(ethoxy)phosphoryl]pentyl]isoindole-1,3-dione
• CAS: 200402-42-2
• 化学式: C₂₁H₃₂NO₆P
• 分子量: 425.462
• InChiKey: QTLYABKKYSUXFE-UHFFFAOYSA-N

物化性质

• 沸点：
  513.093±60.00 °C(Press: 760.00 Torr)(predicted)
• 密度：
  1.166±0.06 g/cm3(Temp: 25 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  29
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  82.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-(5-((1,1-diethoxyethyl)ethoxyphosphoryl)pentyl)phthalimide 在 盐酸 、 sodium hydroxide 、 三甲基氯硅烷 、 chloroamine-T 、 三乙胺 、 N,N-二异丙基乙胺 、 sodium iodide 作用下， 以 甲醇 、 乙醚 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 201.5h， 生成 [125I]-CGP 71872
  参考文献：
  名称：

  Synthesis of the Nanomolar Photoaffinity GABAB Receptor Ligand CGP 71872 Reveals Diversity in the Tissue Distribution of GABAB Receptor Forms

  摘要：

  A radioiodinated probe, [I-125]-CGP 71872, containing an azido group that can be photoactivated, was synthesized and used to characterize GABA(B) receptors. Photoaffinity labeling experiments using crude membranes prepared from rat brain revealed two predominant ligand binding species at similar to 130 and similar to 100 kDa believed to represent the long (GABA(B)R1a) and short (GABA(B)R1b) forms of the receptor. Indeed, these ligand binding proteins were immunoprecipitated using a GABA(B) receptor-specific antibody confirming the receptor specificity of the photoaffinity probe. Most convincingly, [I-125]-CGP 71872 binding was competitively inhibited in a dose-dependent manner by cold CGP 71872, GABA, saclofen, (-)-baclofen, (+)-baclofen and (L)-glutamic acid with a rank order and stereospecificity characteristic of the GABA(B) receptor. Photoaffinity labeling experiments revealed that the recombinant GABA(B)R2 receptor does not bind; [I-125]-CGP 71872, providing surprising and direct evidence that CGP 71872 is a GABA(B)R1 selective antagonist. Photoaffinity labeling experiments using rat tissues showed that both GABA(B)R1a and GABA(B)R1b are co-expressed in the brain, spinal cord, stomach and testis, but only the short GABA(B)R1b receptor form was detected in kidney and liver whereas the long GABA(B)R1a form was selectively expressed in the adrenal gland, pituitary, spleen and prostate. We report herein the synthesis and biochemical characterization of the nanomolar affinity [I-125]-CGP 71872 and CGP 71872 GABA(B)R1 ligands, and differential tissue expression of the long GABA(B)R1a and short GABA(B)R1b receptor forms in rat and dog. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(99)00214-x
• 作为产物：
  描述：

  5-溴戊腈 在 镍 氨 、 sodium hydride 、 sodium carbonate 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 反应 40.0h， 生成 N-(5-((1,1-diethoxyethyl)ethoxyphosphoryl)pentyl)phthalimide
  参考文献：
  名称：

  Ligands for expression cloning and isolation of GABAB receptors

  摘要：

  The scope of the plenary lecture at the occasion of the Xth Meeting on Heterocyclic Structures in Medicinal Chemistry, Palermo 2002, is considerably larger than that of the main lecture at the XVIth International Symposium on Medicinal Chemistry, Bologna 2000, described by Froestl et al. in Farmaco 56 (2001) 101. Additional information is presented, in particular, on the reaction conditions for the 31 step synthesis of the combined affinity chromatography and photoaffinity radioligand [125I]CGP84963 and on the recent developments of the molecular biology of GABA(B) receptors.

  DOI：

  10.1016/s0014-827x(03)00018-1

文献信息

• A Fluorescent Sensor for GABA and Synthetic GABA_B Receptor Ligands
  作者：Anastasiya Masharina、Luc Reymond、Damien Maurel、Keitaro Umezawa、Kai Johnsson

  DOI：10.1021/ja306320s

  日期：2012.11.21

  While gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter, suitable tools to measure its concentration in living cells with high spatiotemporal resolution are missing. Herein, we describe the first ratiometric fluorescent sensor for GABA, dubbed GABA-Snifit, which senses GABA with high specificity and spatiotemporal resolution on the surface of living mammalian cells. GABA-Snifit is a semisynthetic fusion protein containing the GABA(B) receptor, SNAP- and CLIP-tag, a synthetic fluorophore and a fluorescent GABA(B) receptor antagonist. When assembled on cell surfaces, GABA-Snifit displays a GABA-dependent fluorescence emission spectrum in the range of 500-700 nm that permits sensing micromolar to millimolar GABA concentrations. The ratiometric change of the sensor on living cells is 1.8. Furthermore, GABA-Snifit can be utilized to quantify the relative binding affinities of GABA(B) receptor agonists, antagonists and the effect of allosteric modulators. These properties make GABA-Snifit a valuable tool to investigate the role of GABA and GABA(B) in biological systems.
• Ligands for expression cloning and isolation of GABAB receptors
  作者：Wolfgang Froestl、Bernhard Bettler、Helmut Bittiger、Jakob Heid、Klemens Kaupmann、Stuart J. Mickel、Dietrich Strub

  DOI：10.1016/s0014-827x(03)00018-1

  日期：2003.3

  The scope of the plenary lecture at the occasion of the Xth Meeting on Heterocyclic Structures in Medicinal Chemistry, Palermo 2002, is considerably larger than that of the main lecture at the XVIth International Symposium on Medicinal Chemistry, Bologna 2000, described by Froestl et al. in Farmaco 56 (2001) 101. Additional information is presented, in particular, on the reaction conditions for the 31 step synthesis of the combined affinity chromatography and photoaffinity radioligand [125I]CGP84963 and on the recent developments of the molecular biology of GABA(B) receptors.
• Synthesis of the Nanomolar Photoaffinity GABAB Receptor Ligand CGP 71872 Reveals Diversity in the Tissue Distribution of GABAB Receptor Forms
  作者：Michel Belley、Richard Sullivan、Austin Reeves、Jilly Evans、Gary O'Neill、Gordon Y.K. Ng

  DOI：10.1016/s0968-0896(99)00214-x

  日期：1999.12

  A radioiodinated probe, [I-125]-CGP 71872, containing an azido group that can be photoactivated, was synthesized and used to characterize GABA(B) receptors. Photoaffinity labeling experiments using crude membranes prepared from rat brain revealed two predominant ligand binding species at similar to 130 and similar to 100 kDa believed to represent the long (GABA(B)R1a) and short (GABA(B)R1b) forms of the receptor. Indeed, these ligand binding proteins were immunoprecipitated using a GABA(B) receptor-specific antibody confirming the receptor specificity of the photoaffinity probe. Most convincingly, [I-125]-CGP 71872 binding was competitively inhibited in a dose-dependent manner by cold CGP 71872, GABA, saclofen, (-)-baclofen, (+)-baclofen and (L)-glutamic acid with a rank order and stereospecificity characteristic of the GABA(B) receptor. Photoaffinity labeling experiments revealed that the recombinant GABA(B)R2 receptor does not bind; [I-125]-CGP 71872, providing surprising and direct evidence that CGP 71872 is a GABA(B)R1 selective antagonist. Photoaffinity labeling experiments using rat tissues showed that both GABA(B)R1a and GABA(B)R1b are co-expressed in the brain, spinal cord, stomach and testis, but only the short GABA(B)R1b receptor form was detected in kidney and liver whereas the long GABA(B)R1a form was selectively expressed in the adrenal gland, pituitary, spleen and prostate. We report herein the synthesis and biochemical characterization of the nanomolar affinity [I-125]-CGP 71872 and CGP 71872 GABA(B)R1 ligands, and differential tissue expression of the long GABA(B)R1a and short GABA(B)R1b receptor forms in rat and dog. (C) 1999 Elsevier Science Ltd. All rights reserved.