(R)-2-(3-(4-(2-((6-amino-9-((2R,3R,4S,5S)-5-(ethylcarbamoyl)-3,4-dihydroxytetrahydrofuran-2-yl)-9H-purin-2-yl)amino)ethyl)phenyl)propanamido)-5-guanidinopentanoic acid | 1352645-62-5

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: (R)-2-(3-(4-(2-((6-amino-9-((2R,3R,4S,5S)-5-(ethylcarbamoyl)-3,4-dihydroxytetrahydrofuran-2-yl)-9H-purin-2-yl)amino)ethyl)phenyl)propanamido)-5-guanidinopentanoic acid
• 英文别名: (2R)-2-[3-[4-[2-[[6-amino-9-[(2R,3R,4S,5S)-5-(ethylcarbamoyl)-3,4-dihydroxyoxolan-2-yl]purin-2-yl]amino]ethyl]phenyl]propanoylamino]-5-(diaminomethylideneamino)pentanoic acid
• CAS: 1352645-62-5
• 化学式: C₂₉H₄₁N₁₁O₇
• 分子量: 655.714
• InChiKey: FFIPZTPOXCHWRL-IIHBFDQCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  47
• 可旋转键数：
  16
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  291
• 氢给体数：
  9
• 氢受体数：
  13

反应信息

• 作为产物：
  描述：

  (R)-methyl 2-(3-(4-(2-((6-amino-9-((2R,3R,4S,5S)-5-(ethylcarbamoyl)-3,4-dihydroxytetrahydrofuran-2-yl)-9H-purin-2-yl)amino)ethyl)phenyl)propanamido)-5-guanidinopentanoate 在 水 、 sodium hydroxide 作用下， 以 甲醇 为溶剂， 生成 (R)-2-(3-(4-(2-((6-amino-9-((2R,3R,4S,5S)-5-(ethylcarbamoyl)-3,4-dihydroxytetrahydrofuran-2-yl)-9H-purin-2-yl)amino)ethyl)phenyl)propanamido)-5-guanidinopentanoic acid
  参考文献：
  名称：

  Evaluation of Molecular Modeling of Agonist Binding in Light of the Crystallographic Structure of an Agonist-Bound A_2A Adenosine Receptor

  摘要：

  Molecular modeling of agonist binding to the human A(2A) adenosine receptor (AR) was assessed and extended in light of crystallographic structures. Heterocyclic adenine nitrogens of cocrystallized agonist overlaid corresponding positions of the heterocyclic base of a bound triazolotriazine antagonist, and ribose moiety was coordinated in a hydrophilic region, as previously predicted based on modeling using the inactive receptor. Automatic agonist docking of 20 known potent nucleoside agonists to agonist-bound A(2A)AR crystallographic structures predicted new stabilizing protein interactions to provide a structural basis for previous empirical structure activity relationships consistent with previous mutagenesis results. We predicted binding of novel C2 terminal amino acid conjugates of A(2A)AR agonist CGS21680 and used these models to interpret effects on binding affinity of newly synthesized agonists. D-Amino acid conjugates were generally more potent than L-stereoisomers and free terminal carboxylates more potent than corresponding methyl esters. Amino acid moieties were coordinated close to extracellular loops 2 and 3. Thus, molecular modeling is useful in probing ligand recognition and rational design of GPCR-targeting compounds with specific pharmacological profiles.

  DOI：

  10.1021/jm201461q

文献信息

• Evaluation of Molecular Modeling of Agonist Binding in Light of the Crystallographic Structure of an Agonist-Bound A_2A Adenosine Receptor
  作者：Francesca Deflorian、T. Santhosh Kumar、Khai Phan、Zhan-Guo Gao、Fei Xu、Huixian Wu、Vsevolod Katritch、Raymond C. Stevens、Kenneth A. Jacobson

  DOI：10.1021/jm201461q

  日期：2012.1.12

  Molecular modeling of agonist binding to the human A(2A) adenosine receptor (AR) was assessed and extended in light of crystallographic structures. Heterocyclic adenine nitrogens of cocrystallized agonist overlaid corresponding positions of the heterocyclic base of a bound triazolotriazine antagonist, and ribose moiety was coordinated in a hydrophilic region, as previously predicted based on modeling using the inactive receptor. Automatic agonist docking of 20 known potent nucleoside agonists to agonist-bound A(2A)AR crystallographic structures predicted new stabilizing protein interactions to provide a structural basis for previous empirical structure activity relationships consistent with previous mutagenesis results. We predicted binding of novel C2 terminal amino acid conjugates of A(2A)AR agonist CGS21680 and used these models to interpret effects on binding affinity of newly synthesized agonists. D-Amino acid conjugates were generally more potent than L-stereoisomers and free terminal carboxylates more potent than corresponding methyl esters. Amino acid moieties were coordinated close to extracellular loops 2 and 3. Thus, molecular modeling is useful in probing ligand recognition and rational design of GPCR-targeting compounds with specific pharmacological profiles.