6-(piperidin-1-yl)-9-(β-D-ribofuranosyl)purine | 41552-92-5

• 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: 6-(piperidin-1-yl)-9-(β-D-ribofuranosyl)purine
• 英文别名: 6-N-Piperidineadenosine；(2R,3S,4R,5R)-2-(hydroxymethyl)-5-(6-piperidin-1-ylpurin-9-yl)oxolane-3,4-diol
• CAS: 41552-92-5
• 化学式: C₁₅H₂₁N₅O₄
• 分子量: 335.363
• InChiKey: KCBJCVNQLADGGM-SDBHATRESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  117
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  6-(piperidin-1-yl)-9-(β-D-ribofuranosyl)purine 在 对甲苯磺酸一水合物 、 水 、 硝酸 、 乙酸酐 、 三氟乙酸 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 反应 2.0h， 生成 9-(5-Ο-nitro-1β-D-ribofuranosyl)-6-(piperidin-1-yl)-9H-purine
  参考文献：
  名称：

  Discovery of 6-[4-(6-nitroxyhexanoyl)piperazin-1-yl)]-9H-purine, as pharmacological post-conditioning agent

  摘要：

  Novel purine analogues bearing nitrate esters were designed and synthesized in an effort to develop compounds triggering endogenous cardioprotective mechanisms such as ischemic preconditioning (IPC) or postconditioning (PostC). The majority of the compounds reduced infarct size compared to the control group in anesthetized rabbits, whereas administration of the most active analogue 16 at a dose of 3.8 mu mol/kg resulted on a significant reduction of infarct size, compared to PostC group (13.4 +/- 1.9% vs 26.4 +/- 2.3%). These findings introduce a novel class of promising pharmacological compounds that could be used as mimics or enhancers of PostC. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.07.037
• 作为产物：
  描述：

  四乙酰核糖 在 硫酸氢铵 、 sodium methylate 、 六甲基二硅氮烷 作用下， 以 甲醇 为溶剂， 反应 1.0h， 生成 6-(piperidin-1-yl)-9-(β-D-ribofuranosyl)purine
  参考文献：
  名称：

  Discovery of 6-[4-(6-nitroxyhexanoyl)piperazin-1-yl)]-9H-purine, as pharmacological post-conditioning agent

  摘要：

  Novel purine analogues bearing nitrate esters were designed and synthesized in an effort to develop compounds triggering endogenous cardioprotective mechanisms such as ischemic preconditioning (IPC) or postconditioning (PostC). The majority of the compounds reduced infarct size compared to the control group in anesthetized rabbits, whereas administration of the most active analogue 16 at a dose of 3.8 mu mol/kg resulted on a significant reduction of infarct size, compared to PostC group (13.4 +/- 1.9% vs 26.4 +/- 2.3%). These findings introduce a novel class of promising pharmacological compounds that could be used as mimics or enhancers of PostC. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.07.037

文献信息

• Anti-HCV nucleoside derivatives
  申请人：——

  公开号：US20030008841A1

  公开（公告）日：2003-01-09

  The present invention comprises novel and known purine and pyrimidine nucleoside derivatives which have been discovered to be active against hepatitis C virus (HCV). The use of these derivatives for the treatment of HCV infection is claimed as are the novel nucleoside derivatives disclosed herein.

  本发明涉及新颖和已知的嘌呤和嘧啶核苷衍生物，已发现这些衍生物对丙型肝炎病毒（HCV）具有活性。本发明声明利用这些衍生物治疗HCV感染，以及本文所披露的新颖核苷衍生物。
• 6-Substituted purines as ROCK inhibitors with anti-metastatic activity
  作者：Jiří Voller、Lenka Zahajská、Lucie Plíhalová、Jana Jeřábková、David Burget、Andreea Csilla Pataki、Vladimír Kryštof、Marek Zatloukal、Jan Brábek、Daniel Rösel、Václav Mik、Martin Tkáč、Tomáš Pospíšil、Tomáš Gucký、Karel Doležal、Miroslav Strnad

  DOI：10.1016/j.bioorg.2019.103005

  日期：2019.9

  contractility, shape, motility, and invasion of cells. We explored the relationships between structure and anti-ROCK2 activity in a group of purine derivatives substituted at the C6 atom by piperidin-1-yl or azepan-1-yl groups. Structure-activity relationship (SAR) analyses suggested that anti-ROCK activity is retained, and may be further increased, by substitution of the parent compounds at the C2 atom or by expansion

  Rho相关的丝氨酸/苏氨酸激酶（ROCKs）是肌动蛋白细胞骨架的主要调节剂，可调节细胞的收缩性，形状，运动性和侵袭性。我们探索了在一组碳素原子上被哌啶-1-基或氮杂-1-基取代的嘌呤衍生物的结构与抗ROCK2活性之间的关系。结构活性关系（SAR）分析表明，通过在C2原子处取代母体化合物或通过扩展C6侧链，可以保留抗ROCK活性，并且可以进一步提高抗ROCK活性。这些ROCK抑制剂可以在细胞内达到有效浓度，这可以通过ROCK靶MLC磷酸化的减少以及抑制ROCK依赖的黑色素瘤细胞在胶原蛋白基质中的侵入来证明。
• Pd/PTABS: Catalyst for Room Temperature Amination of Heteroarenes
  作者：Siva Sankar Murthy Bandaru、Shatrughn Bhilare、Nicolas Chrysochos、Vijay Gayakhe、Ivan Trentin、Carola Schulzke、Anant R. Kapdi

  DOI：10.1021/acs.orglett.7b03854

  日期：2018.1.19

  A mild and highly efficient catalytic amination procedure for chloroheteroarenes at ambient temperature using the Pd/PTABS catalytic system is reported. The protocol is selective for the amination of chloroheteroarenes using secondary amines such as piperidine, pyrrolidine, and several others. The exceptional mildness of the developed protocol is beneficial for the synthesis of a crucial Buparlisib

  据报道，在室温下使用Pd / PTABS催化体系进行的氯杂芳烃温和高效的催化胺化程序。该方案对于使用仲胺（例如哌啶，吡咯烷和其他几种胺）进行氯杂芳烃的胺化反应具有选择性。所开发方案的非凡温和性，对于关键的布氏替尼中间体的合成以及以竞争性收率进行阿格列汀的正式合成都是有益的。
• Testing Nucleoside Analogues as Inhibitors of <i>Bacillus anthracis</i> Spore Germination <i>In Vitro</i> and in Macrophage Cell Culture
  作者：Zadkiel Alvarez、Kyungae Lee、Ernesto Abel-Santos

  DOI：10.1128/aac.01029-10

  日期：2010.12

  Bacillus anthracis , the etiological agent of anthrax, has a dormant stage in its life cycle known as the endospore. When conditions become favorable, spores germinate and transform into vegetative bacteria. In inhalational anthrax, the most fatal manifestation of the disease, spores enter the organism through the respiratory tract and germinate in phagosomes of alveolar macrophages. Germinated cells can then produce toxins and establish infection. Thus, germination is a crucial step for the initiation of pathogenesis. B. anthracis spore germination is activated by a wide variety of amino acids and purine nucleosides. Inosine and l -alanine are the two most potent nutrient germinants in vitro . Recent studies have shown that germination can be hindered by isomers or structural analogues of germinants. 6-Thioguanosine (6-TG), a guanosine analogue, is able to inhibit germination and prevent B. anthracis toxin-mediated necrosis in murine macrophages. In this study, we screened 46 different nucleoside analogues as activators or inhibitors of B. anthracis spore germination in vitro . These compounds were also tested for their ability to protect the macrophage cell line J774a.1 from B. anthracis cytotoxicity. Structure-activity relationship analysis of activators and inhibitors clarified the binding mechanisms of nucleosides to B. anthracis spores. In contrast, no structure-activity relationships were apparent for compounds that protected macrophages from B. anthracis -mediated killing. However, multiple inhibitors additively protected macrophages from B. anthracis .

  摘要 炭疽杆菌 炭疽杆菌是炭疽病的病原体，在其生命周期中有一个称为内生孢子的休眠阶段。当条件有利时，孢子发芽并转化为无性繁殖细菌。在吸入性炭疽这种最致命的疾病中，孢子通过呼吸道进入机体，并在肺泡巨噬细胞的吞噬体中发芽。发芽的细胞随后可产生毒素并形成感染。因此，发芽是启动致病机制的关键步骤。 炭疽杆菌 孢子萌发是由多种氨基酸和嘌呤核苷激活的。肌苷和 l -丙氨酸是两种最有效的营养萌发剂 体外 .最近的研究表明，萌芽剂的异构体或结构类似物会阻碍萌芽。6-Thioguanosine (6-TG)是一种鸟苷类似物，能够抑制萌芽并防止炭疽杆菌的萌发。 炭疽杆菌 毒素介导的小鼠巨噬细胞坏死。在这项研究中，我们筛选了 46 种不同的核苷类似物作为炭疽杆菌毒素的激活剂或抑制剂。 炭疽杆菌 孢子萌发 体外 .我们还测试了这些化合物保护巨噬细胞系 J774a.1 免受炭疽杆菌感染的能力。 炭疽杆菌 细胞毒性的能力。激活剂和抑制剂的结构-活性关系分析阐明了核苷与炭疽杆菌的结合机制。 炭疽杆菌 孢子的结合机制。与此相反，保护巨噬细胞免受炭疽杆菌侵袭的化合物却没有明显的结构-活性关系。 炭疽杆菌 -介导的杀灭。然而，多种抑制剂相加可保护巨噬细胞免受 炭疽杆菌 .
• Mild and Efficient Functionalization at C6 of Purine 2‘-Deoxynucleosides and Ribonucleosides¹
  作者：Xiaoyu Lin、Morris J. Robins

  DOI：10.1021/ol000255h

  日期：2000.11.1

  [reaction: see text] Treatment of sugar-protected inosine and 2'-deoxyinosine derivatives with a cyclic secondary amine or imidazole and I(2)/Ph(3)P/EtN(i-Pr)(2)/(CH(2)Cl(2) or toluene) gave quantitative conversions into 6-N-(substituted)purine nucleosides. S(N)Ar reactions with 6-(imidazol-1-yl) derivatives gave 6-(N, O, or S)-substituted products. The 6-(benzylsulfonyl) group underwent S(N)Ar displacement

  [反应：请参见文本]用环状仲胺或咪唑和I（2）/ Ph（3）P / EtN（i-Pr）（2）/（CH（ 2）Cl（2）或甲苯）定量转化为6-N-（取代）嘌呤核苷。与6-（咪唑-1-基）衍生物的S（N）Ar反应得到6-（N，O或S）-取代的产物。在环境温度下用芳基胺对6-（苄基磺酰基）进行S（N）Ar取代。