4-[2-[[6-氨基-9-(N-乙基-BETA-D-呋喃核糖酰胺基)-9H-嘌呤-2-基]氨基]乙基]苯丙酸 | 120225-54-9

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 中文名称: 4-[2-[[6-氨基-9-(N-乙基-BETA-D-呋喃核糖酰胺基)-9H-嘌呤-2-基]氨基]乙基]苯丙酸
• 英文名称: 2-[4-(carboxyethyl)phenylethylamino]-5'-N-ethylcarboxamidoadenosine
• 英文别名: CGS 21680；3-{4-[2-({6-amino-9-[(2R,3R,4S,5S)-5-(ethylcarbamoyl)-3,4-dihydroxytetrahydro-2-furanyl]-9H-purin-2-yl}amino)ethyl]phenyl}propanoic acid；3-[4-[2-[ [6-amino-9-[(2R,3R,4S,5S)-5-(ethylcarbamoyl)-3,4-dihydroxy-oxolan-2-yl]purin-2-yl]amino]ethyl]phenyl]propanoic acid；3-[4-[2-[ [6-amino-9-[(2R,3R,4S,5S)-5-(ethylcarbamoyl)-3,4-dihydroxyoxolan-2-yl]purin-2-yl]amino]ethyl]phenyl]propanoic acid；3-[4-[2-[[6-amino-9-[(2R,3R,4S,5S)-5-(ethylcarbamoyl)-3,4-dihydroxyoxolan-2-yl]purin-2-yl]amino]ethyl]phenyl]propanoic acid；4-[2-[[6-amino-9-(N-ethyl-β-D-ribofuranuronamidosyl)-9H-purin-2-yl]amino]ethyl]benzenepropanoic acid hydrochloride；2-(4-(2-Carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine
• CAS: 120225-54-9
• 化学式: C₂₃H₂₉N₇O₆
• 分子量: 499.527
• InChiKey: PAOANWZGLPPROA-RQXXJAGISA-N

物化性质

• 密度：
  1.60
• 溶解度：
  在DMSO中溶解度高达3.4mg/mL，在45%(w/v)2-羟丙基β-环糊精水溶液中溶解度高达20mg/mL。

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  36
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  198
• 氢给体数：
  6
• 氢受体数：
  11

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  2-8℃

制备方法与用途

CGS 21680是一种特异性激活腺苷A2A受体的化合物，常被用于神经疾病的科研中。

反应信息

• 作为反应物：
  描述：

  4-[2-[[6-氨基-9-(N-乙基-BETA-D-呋喃核糖酰胺基)-9H-嘌呤-2-基]氨基]乙基]苯丙酸 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N'-二环己基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 4-(3-(4-(2-((6-amino-9-((2R,5S)-5-(ethylcarbamoyl)-3,4-dihydroxytetrahydrofuran-2-yl)-9H-purin-2-yl)amino)ethyl)phenyl)propanamido)-2-nitrophenyl 5-azidopentanoate
  参考文献：
  名称：

  Structure-Based Design of Reactive Nucleosides for Site-Specific Modification of the A_2A Adenosine Receptor

  摘要：

  Adenosine receptors (ARs) are members of the G protein-coupled receptor (GPCR) superfamily and have shown much promise as therapeutic targets. We have used an agonist-bound A2AAR X-ray crystallographic structure to design a chemically reactive agonist for site-specific chemical modification of the receptor. To further explore and chemically engineer its binding cavity, a 2-nitrophenyl active ester was attached through an elongated chain at adenine C2 position. This general structure was designed for irreversible transfer of a terminal acyl group to a nucleophilic amino group on the A2AAR. Preincubation with several O-acyl derivatives prevented radioligand binding that was not regenerated upon extensive washing. In silico receptor docking suggested two lysine residues (second extracellular loop) as potential target sites for an O-acetyl derivative (MRS5854, 3a), and site-directed mutagenesis indicated that K153 but not K150 is essential. Similarly, a butyl azide for click reaction was incorporated in the active ester moiety (3b). These promising results indicate a stable, covalent modification of the receptor by several reactive adenosine derivatives, which could be chemical tools for future imaging, structural probing, and drug discovery. Thus, structure-based ligand design has guided the site-specific modification of a GPCR.

  DOI：

  10.1021/ml5002486
• 作为产物：
  描述：

  2-<<4-<2-(tert-butoxycarbonyl)etyl>phenethyl>amino>-2',3'-O-isopropylideneadenosine-5'-N-ethylcarboxamide 生成 4-[2-[[6-氨基-9-(N-乙基-BETA-D-呋喃核糖酰胺基)-9H-嘌呤-2-基]氨基]乙基]苯丙酸
  参考文献：
  名称：

  HUTCHISON, ALAN J.;WILLIAMS, MICHAEL;JESUS, REYNALDA DE;RINA, YOKOYAMA;OE+, J. MED. CHEM., 33,(1990) N, C. 1919-1924

  摘要：

  DOI：
• 作为试剂：
  描述：

  、 腺嘌呤 、 膦酰甲酸 、 4-(3-丁氧基-4-甲氧基苯基)咪唑啶-2-酮 、 腺苷 在 腺苷 、 腺苷环磷酸酯 、 4-[2-[[6-氨基-9-(N-乙基-BETA-D-呋喃核糖酰胺基)-9H-嘌呤-2-基]氨基]乙基]苯丙酸 、 高氯酸 、 三羟甲基氨基甲烷盐酸盐 作用下， 反应 17.25h， 以[3H]cAMP was isolated by sequential chromatography on Dowex AG的产率得到腺苷环磷酸酯
  参考文献：
  名称：

  Use of a compound for enhancing the expression of membrane proteins on the cell surface

  摘要：

  本发明涉及使用一种刺激细胞去泛素化活性的化合物，用于制造一种药物，以增强细胞表面的完整膜蛋白的表达。特别地，本发明涉及使用这种化合物制造一种药物，用于治疗来自囊性纤维化、尿崩症、高胆固醇血症和长QT综合症2等疾病或症状的药物。

  公开号：

  US20060008454A1

文献信息

• Edaravone-Encapsulated Agonistic Micelles Rescue Ischemic Brain Tissue by Tuning Blood-Brain Barrier Permeability
  作者：Qu Jin、Yu Cai、Sihan Li、Haoran Liu、Xingyu Zhou、Chunqiang Lu、Xihui Gao、Jun Qian、Jun Zhang、Shenghong Ju、Cong Li

  DOI：10.7150/thno.18219

  日期：——

  Thrombolysis has been a standard treatment for ischemic stroke. However, only 2-7% patients benefit from it because the thrombolytic agent has to be injected within 4.5 h after the onset of symptoms to avoid the increasing risk of intracerebral hemorrhage. As the only clinically approved neuroprotective drug, edaravone (EDV) rescues ischemic brain tissues by eradicating over-produced reactive oxygen species (ROS) without the limitation of therapeutic time-window. However, EDV's short circulation half-life and inadequate cerebral uptake attenuate its therapeutic efficacy. Here we developed an EDV-encapsulated agonistic micelle (EDV-AM) to specifically deliver EDV into brain ischemia by actively tuning blood-brain barrier (BBB) permeability. The EDV-AM actively up-regulated endothelial monolayer permeability in vitro. HPLC studies showed that EDV-AM delivered more EDV into brain ischemia than free EDV after intravenous injection. Magnetic resonance imaging also demonstrated that EDV-AM more rapidly salvaged ischemic tissue than free EDV. Diffusion tensor imaging indicated the highest efficiency of EDV-AM in accelerating axonal remodeling in the ipsilesional white matter and improving functional behaviors of ischemic stroke models. The agonistic micelle holds promise to improve the therapeutic efficiency of ischemic stroke patients who miss the thrombolytic treatment.

  溶栓一直是缺血性中风的标准治疗方法。然而，由于溶栓药物必须在症状出现后 4.5 小时内注射，以避免增加脑内出血的风险，因此只有 2-7% 的患者从中受益。作为唯一获得临床批准的神经保护药物，依达拉奉（EDV）通过消除过度产生的活性氧（ROS）来挽救缺血的脑组织，而不受治疗时间窗口的限制。然而，EDV 在血液循环中的半衰期较短，大脑摄取不足，从而削弱了其疗效。在这里，我们开发了一种EDV胶囊激动剂胶束（EDV-AM），通过主动调节血脑屏障（BBB）的通透性，将EDV特异性地输送到脑缺血部位。EDV-AM 可在体外积极上调内皮单层的通透性。高效液相色谱研究表明，静脉注射后，EDV-AM 比游离 EDV 向脑缺血部位输送更多的 EDV。磁共振成像也表明，与游离 EDV 相比，EDV-AM 能更快地挽救缺血组织。扩散张量成像显示，EDV-AM 在加速同侧白质轴突重塑和改善缺血性中风模型的功能行为方面效率最高。这种激动剂胶束有望提高错过溶栓治疗的缺血性中风患者的治疗效率。
• New compositions and methods for the treatment of inflammation
  申请人：Rieger M. Jayson

  公开号：US20070032450A1

  公开（公告）日：2007-02-08

  The present invention describes combinations of A 2A adenosine receptor agonists and anti-inflammatory compounds for the inhibition of an inflammatory response in mammalian tissue.

  本发明描述了A2A腺苷受体激动剂和抗炎化合物的组合物，用于抑制哺乳动物组织中的炎症反应。
• THERAPEUTIC AGENT FOR MIGRAINE
  申请人：Ikeda Junichi

  公开号：US20110183992A1

  公开（公告）日：2011-07-28

  Provided are therapeutic and/or preventive agents for migraine which comprise, as an active ingredient, a compound having a selective adenosine A 2A receptor antagonistic activity or a pharmaceutically acceptable salt thereof; therapeutic and/or preventive agents for migraine which comprise, as an active ingredient, a compound having a selective adenosine A 2A receptor antagonistic activity, which has an affinity for the adenosine A 2A receptor 10 times or higher than that for the adenosine A 1 receptor, or a pharmaceutically acceptable salt thereof; and the like.

  提供了治疗和/或预防偏头痛的药物，其作为活性成分包含具有选择性腺苷A2A受体拮抗活性的化合物或其药学上可接受的盐；作为活性成分包含具有选择性腺苷A2A受体拮抗活性的化合物的治疗和/或预防偏头痛药物，其与腺苷A1受体相比具有10倍或更高的亲和力，或其药学上可接受的盐；等等。
• NEW COMPOSITIONS AND METHODS FOR THE TREATMENT OF INFLAMMATION
  申请人：Rieger Jayson M.

  公开号：US20100166698A1

  公开（公告）日：2010-07-01

  The present invention describes combinations of A 2A adenosine receptor agonists and anti-inflammatory compounds for the inhibition of an inflammatory response in mammalian tissue.

  本发明描述了A2A腺苷受体激动剂和抗炎化合物的组合，用于抑制哺乳动物组织中的炎症反应。
• Therapeutic agent for migraine
  申请人：Ikeda Junichi

  公开号：US09254283B2

  公开（公告）日：2016-02-09

  Provided are therapeutic and/or preventive agents for migraine which comprise, as an active ingredient, a compound having a selective adenosine A2A receptor antagonistic activity or a pharmaceutically acceptable salt thereof; therapeutic and/or preventive agents for migraine which comprise, as an active ingredient, a compound having a selective adenosine A2A receptor antagonistic activity, which has an affinity for the adenosine A2A receptor 10 times or higher than that for the adenosine A1 receptor, or a pharmaceutically acceptable salt thereof; and the like.

  提供了治疗和/或预防偏头痛的药物，其包括作为活性成分的具有选择性腺苷A2A受体拮抗活性或其药学上可接受的盐的化合物；作为活性成分的具有选择性腺苷A2A受体拮抗活性的化合物，其对腺苷A1受体的亲和力比对腺苷A2A受体高10倍或更高，或其药学上可接受的盐；等等。