8-pyridin-2-yl-7(9)H-purine | 15846-75-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 8-pyridin-2-yl-7(9)H-purine
• 英文别名: 8-pyridin-2-yl-7H-purine
• CAS: 15846-75-0
• 化学式: C₁₀H₇N₅
• 分子量: 197.199
• InChiKey: IKLBKJSFSNHGKO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  67.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4,5-二氨基嘧啶 、 2-脒基吡啶盐酸盐 在 sodium acetate 作用下， 以62%的产率得到8-pyridin-2-yl-7(9)H-purine
  参考文献：
  名称：

  Metal-Mediated Inhibition of Escherichia coli Methionine Aminopeptidase:  Structure−Activity Relationships and Development of a Novel Scoring Function for Metal−Ligand Interactions

  摘要：

  We report the discovery of thiabendazole as a potent inhibitor (K-i = 0.4 mu M) of Escherichia coli methionine aminopeptidase (ecMetAP) and the synthesis and pharmacological evaluation of thiabendazole congeners with activity in the upper nanomolar range. Elucidation of the X-ray structure of ecMetAP in complex with thiabendazole and an unrelated inhibitor that was independently described by another group showed that that both compounds bind to an additional Coll ion at the entrance of the active site. This unexpected finding explains the inactivity of the compounds under in vivo conditions. It also allows us to discuss the structure-activity relationships of this series of compounds in a meaningful way, based upon docking runs with an auxiliary metal ion. We describe a new scoring function for the evaluation of metal-mediated inhibitor binding that, unlike the previously used scoring function implemented in the docking program, allows us to distinguish between active and inactive compounds. Finally, conclusions for the structure-based design of in vivo-active inhibitors of ecMetAP are drawn.

  DOI：

  10.1021/jm050476z

文献信息

• Selective Preparations of Purine Nucleosides and Nucleotides: Reagents and Methods
  申请人：Zhong Minghong

  公开号：US20150376219A1

  公开（公告）日：2015-12-31

  A process of regiospecific synthesis of N-9 purine nucleoside analogs in either solution or solid phase synthesis is described. The introduction of the sugar moiety or its analogue on to a 6-heteroarylium purine or its mesomeric betaine so that formation of only the N-9 position regioisomers of the purine nucleoside analogs (either D or L enantiomers) is obtained. This regiospecific introduction of the sugar moiety allows the synthesis of purine nucleoside analogs in high yields without formation of the N-7-positional regioisomers, while the 6-heteroaryliums are leaving groups facilitated for nucleophilic displacement. Solid supported 6-heterarylium purine bases can be used for purine based library synthesis and synthesis of nucleotide monophosphates and polyphosphates. Processes for providing novel 6-heteroarylium purines and their corresponding mesomeric betaines for the regiospecific synthesis of N-9 purine nucleoside analogs and nucleotides are described.

  描述了一种在溶液或固相合成中合成N-9嘌呤核苷类似物的位置特异性合成过程。将糖基或其类似物引入到6-杂环嘌呤或其共振甲基盐上，从而仅形成嘌呤核苷类似物的N-9位置异构体（D或L对映体）。这种糖基的位置特异性引入允许在高产率下合成嘌呤核苷类似物，而不形成N-7位置异构体，而6-杂环嘌呤是易于亲核置换的离去基团。固相支持的6-杂环嘌呤碱可以用于嘌呤基库合成和核苷酸一磷酸和多磷酸的合成。描述了提供新颖的6-杂环嘌呤及其相应的共振甲基盐以用于N-9嘌呤核苷类似物和核苷酸的位置特异性合成的过程。
• Conformationally Constrained Analytical Probes
  申请人：Lyon Robert

  公开号：US20080269065A1

  公开（公告）日：2008-10-30

  There is disclosed probes bearing partial metal chelators that in some embodiments are conformationally constrained. In certain embodiments such probes are useful in methods for the detection of a specific target molecule. These target molecules may include oligonucleotides, peptides, proteins, polysaccharides, or small molecules. There is further disclosed the use of probes with partial metal chelators engaged in a coordination complex with one another that imposes a structural constraint in the probe and increases the specificity factor of the probe.

  本文披露了带有部分金属螯合剂的探针，其中在某些实施例中具有构象约束。在某些实施例中，这些探针可用于检测特定目标分子的方法中。这些目标分子可以包括寡核苷酸、肽、蛋白质、多糖或小分子。本文还披露了使用带有部分金属螯合剂的探针参与配位复合物的方法，该复合物在探针中施加结构约束并增加探针的特异性因子。
• Metal-Mediated Inhibition of <i>Escherichia </i><i>c</i><i>oli</i> Methionine Aminopeptidase:  Structure−Activity Relationships and Development of a Novel Scoring Function for Metal−Ligand Interactions
  作者：Rolf Schiffmann、Alexander Neugebauer、Christian D. Klein

  DOI：10.1021/jm050476z

  日期：2006.1.1

  We report the discovery of thiabendazole as a potent inhibitor (K-i = 0.4 mu M) of Escherichia coli methionine aminopeptidase (ecMetAP) and the synthesis and pharmacological evaluation of thiabendazole congeners with activity in the upper nanomolar range. Elucidation of the X-ray structure of ecMetAP in complex with thiabendazole and an unrelated inhibitor that was independently described by another group showed that that both compounds bind to an additional Coll ion at the entrance of the active site. This unexpected finding explains the inactivity of the compounds under in vivo conditions. It also allows us to discuss the structure-activity relationships of this series of compounds in a meaningful way, based upon docking runs with an auxiliary metal ion. We describe a new scoring function for the evaluation of metal-mediated inhibitor binding that, unlike the previously used scoring function implemented in the docking program, allows us to distinguish between active and inactive compounds. Finally, conclusions for the structure-based design of in vivo-active inhibitors of ecMetAP are drawn.