3-(1-(R)-((3-((5-aminopentyl)hydroxyphosphoryl)-2-(S)-hydroxypropyl)amino)ethyl)benzoic acid dihydrochloride

• 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-aminopentyl)hydroxyphosphoryl)-2-(S)-hydroxypropyl)amino)ethyl)benzoic acid dihydrochloride
• 英文别名: 3-[(1R)-1-[[(2S)-3-[5-aminopentyl(hydroxy)phosphoryl]-2-hydroxypropyl]amino]ethyl]benzoic acid;hydrochloride
• 化学式: C₁₇H₂₉N₂O₅P*2ClH
• 分子量: 445.323
• InChiKey: HPRXUENAFJICGB-CACIRBSMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.22
• 重原子数：
  26
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  133
• 氢给体数：
  6
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-(1-(R)-((3-((5-aminopentyl)hydroxyphosphoryl)-2-(S)-hydroxypropyl)amino)ethyl)benzoic acid dihydrochloride 在 chloroamine-T 、 N,N-二异丙基乙胺 、 sodium iodide 作用下， 以 甲醇 、 水 为溶剂， 反应 3.0h， 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：

  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 、 乙醇 、 水 为溶剂， 反应 122.6h， 生成 3-(1-(R)-((3-((5-aminopentyl)hydroxyphosphoryl)-2-(S)-hydroxypropyl)amino)ethyl)benzoic acid dihydrochloride
  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

• Metabotropic GABA [B] receptors, receptor-specific ligands and their uses
  申请人：——

  公开号：US20020091250A1

  公开（公告）日：2002-07-11

  The present invention provides purified GABA B receptors and receptor proteins derived from rat and human sources, as well as nucleic acids which encode such proteins. The proteins and nucleic acids of the invention share significant homology with the GABA B receptor and the DNA encoding it as specifically disclosed herein. The invention moreover provides methods for isolating other members of the GABA B receptor family using DNA cloning technology and probes derived from the sequences provided herein, as well as novel members of the GABA B receptor family isolated by such methods. Furthermore, the invention relates to the use of GABA B receptors and receptor proteins and cells transformed with a gene encoding a GABA B receptor protein in a method for identifying and characterising compounds which modulate the activity of the GABA B receptor, such as GABA B receptor agonists and antagonists, which may be useful as pharmacological agents for the treatment of disorders associated with the central and peripheral nervous systems.

  本发明提供了从大鼠和人类来源纯化的GABAB受体和受体蛋白，以及编码这些蛋白的核酸。本发明的蛋白质和核酸与此处明确披露的GABAB受体及其编码的DNA具有显著的同源性。此外，本发明提供了使用DNA克隆技术和从此处提供的序列衍生的探针来分离GABAB受体家族的其他成员的方法，以及通过这些方法分离的GABAB受体家族的新成员。此外，本发明涉及使用GABAB受体和受体蛋白以及转化有编码GABAB受体蛋白的基因的细胞的方法，用于识别和表征调节GABAB受体活性的化合物，例如GABAB受体激动剂和拮抗剂，这些化合物可用作治疗与中枢和外周神经系统相关的疾病的药物。
• Activity-Based Probe for Specific Photoaffinity Labeling γ-Aminobutyric Acid B (GABA_B) Receptors on Living Cells: Design, Synthesis, and Biological Evaluation
  作者：Xin Li、Jian-Hua Cao、Ying Li、Philippe Rondard、Yang Zhang、Ping Yi、Jian-Feng Liu、Fa-Jun Nan

  DOI：10.1021/jm800140f

  日期：2008.6.1

  synthesized, characterized, and applied to photoaffinity label the GABA(B) receptors transiently expressed in Chinese hamster ovary (CHO) cells. The probe exhibits specific binding activity at the ligand-binding pocket of GB1 subunits and high specificity of photoaffinity labeling, which makes the probe valuable for studying the localization and function of GABA(B) receptors on living cells.

  设计，合成，表征，基于三模活动的探针，并将其应用于光亲和标记的中国仓鼠卵巢（CHO）细胞中瞬时表达的GABA（B）受体。该探针在GB1亚基的配体结合口袋处表现出特异性结合活性，并具有高光亲和标记特异性，这使得该探针对于研究GABA（B）受体在活细胞上的定位和功能具有重要价值。
• 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.
• METABOTROPIC GABA(B) RECEPTORS, RECEPTOR-SPECIFIC LIGANDS AND THEIR USES
  申请人：Novartis AG

  公开号：EP0907731B1

  公开（公告）日：2005-03-02
• US7119189B2
  申请人：——

  公开号：US7119189B2

  公开（公告）日：2006-10-10