3-(1-(R)-((3-((5-(4-azido-2-hydroxybenzoylamino)pentyl)hydroxyphosphoryl)-2-(S)-hydroxypropyl)amino)ethyl)benzoic acid | 200402-52-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-(1-(R)-((3-((5-(4-azido-2-hydroxybenzoylamino)pentyl)hydroxyphosphoryl)-2-(S)-hydroxypropyl)amino)ethyl)benzoic acid
• 英文别名: 3-[(1R)-1-[[(2S)-3-[5-[(4-azido-2-hydroxybenzoyl)amino]pentyl-hydroxyphosphoryl]-2-hydroxypropyl]amino]ethyl]benzoic acid
• CAS: 200402-52-4
• 化学式: C₂₄H₃₂N₅O₇P
• 分子量: 533.521
• InChiKey: NLDSYLGLVYGOFU-UZLBHIALSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  37
• 可旋转键数：
  15
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  171
• 氢给体数：
  6
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  3-(1-(R)-((3-((5-(4-azido-2-hydroxybenzoylamino)pentyl)hydroxyphosphoryl)-2-(S)-hydroxypropyl)amino)ethyl)benzoic acid 在 chloroamine-T 、 sodium iodide 作用下， 以 甲醇 、 水 为溶剂， 反应 3.0h， 以58%的产率得到[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：

  3-乙酰苯腈 在 盐酸 、 sodium hydroxide 、 偶氮二甲酸二异丙酯 、 一水合肼 、 N,N-二异丙基乙胺 、 三苯基膦 、 (-)-diisopinocamphenylborane chloride 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 水 为溶剂， 反应 122.6h， 生成 3-(1-(R)-((3-((5-(4-azido-2-hydroxybenzoylamino)pentyl)hydroxyphosphoryl)-2-(S)-hydroxypropyl)amino)ethyl)benzoic acid
  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

文献信息

• 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.