6-benzylthio-purine riboside

• 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-benzylthio-purine riboside
• 英文别名: 6-(benzylthio)-9-(β-D-ribofuranosyl)purine；6-Benzylthioinosine；(2R,3R,4S,5R)-2-(6-benzylsulfanylpurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol
• 化学式: C₁₇H₁₈N₄O₄S
• 分子量: 374.42
• InChiKey: OMJRXFOHHLLDFR-LSCFUAHRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  139
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  亚甲基双膦酰二氯 、 6-benzylthio-purine riboside 在 磷酸三甲酯 、 三乙基碳酸氢铵缓冲液 作用下， 反应 1.75h， 生成 S⁶-benzylpurine riboside-5′-O-[(phosphonomethyl)phosphonic acid]
  参考文献：
  名称：

  α,β-Methylene-ADP (AOPCP) Derivatives and Analogues: Development of Potent and Selective ecto-5′-Nucleotidase (CD73) Inhibitors

  摘要：

  ecto-5'-Nucleotidase (eN, CD73) catalyzes the hydrolysis of extracellular AMP to adenosine. eN inhibitors have potential for use as cancer therapeutics. The eN inhibitor alpha,beta-methylene-ADP (AOPCP, adenosine-5'-O-[(phosphonomethyl)phosphonic acid]) was used as a lead structure, and derivatives modified in various positions were prepared. Products were tested at rat recombinant eN. 6-(Ar)alkylamino substitution led to the largest improvement in potency. N-6-Monosubstitution was superior to symmetrical N-6,N-6-disubstitution. The most potent inhibitors were N-6-(4chlorobenzyl)-(10l, PSB-12441, K-i 7.23 n.M), N-6-phenylethyl(10h, PSB-12425, K-i 8.04 nM), and N-6-benzyl-adenosine-5'-O[(phosphonomethyl)phosphonic acid] (10g, PSB-12379, K-i 9.03 nM). Replacement of the 6-NH group in 10g by 0 (10q, PSB-12431) or S (10r, PSB-12553) yielded equally potent inhibitors (10q, 9.20 nM; 10r, 9.50 aM). Selected compounds investigated at the human enzyme did not show species differences; they displayed high selectivity versus other ecto-nudeotidases and ADP-activated P2Y receptors. Moreover, high metabolic stability was observed. These compounds represent the most potent eN inhibitors described to date.

  DOI：

  10.1021/acs.jmedchem.5b00802
• 作为产物：
  描述：

  6-氯嘌呤核苷 在 potassium carbonate 作用下， 以 乙醇 为溶剂， 反应 1.17h， 生成 6-benzylthio-purine riboside
  参考文献：
  名称：

  α,β-Methylene-ADP (AOPCP) Derivatives and Analogues: Development of Potent and Selective ecto-5′-Nucleotidase (CD73) Inhibitors

  摘要：

  ecto-5'-Nucleotidase (eN, CD73) catalyzes the hydrolysis of extracellular AMP to adenosine. eN inhibitors have potential for use as cancer therapeutics. The eN inhibitor alpha,beta-methylene-ADP (AOPCP, adenosine-5'-O-[(phosphonomethyl)phosphonic acid]) was used as a lead structure, and derivatives modified in various positions were prepared. Products were tested at rat recombinant eN. 6-(Ar)alkylamino substitution led to the largest improvement in potency. N-6-Monosubstitution was superior to symmetrical N-6,N-6-disubstitution. The most potent inhibitors were N-6-(4chlorobenzyl)-(10l, PSB-12441, K-i 7.23 n.M), N-6-phenylethyl(10h, PSB-12425, K-i 8.04 nM), and N-6-benzyl-adenosine-5'-O[(phosphonomethyl)phosphonic acid] (10g, PSB-12379, K-i 9.03 nM). Replacement of the 6-NH group in 10g by 0 (10q, PSB-12431) or S (10r, PSB-12553) yielded equally potent inhibitors (10q, 9.20 nM; 10r, 9.50 aM). Selected compounds investigated at the human enzyme did not show species differences; they displayed high selectivity versus other ecto-nudeotidases and ADP-activated P2Y receptors. Moreover, high metabolic stability was observed. These compounds represent the most potent eN inhibitors described to date.

  DOI：

  10.1021/acs.jmedchem.5b00802

文献信息

• Microwave-Promoted “One-Pot” Synthesis of 4-Nitrobenzylthioinosine Analogues Using Thiourea as a Sulfur Precursor
  作者：Hong-Ying Niu、Chao Xia、Gui-Rong Qu、Shan Wu、Yi Jiang、Xin Jin、Hai-Ming Guo

  DOI：10.1002/asia.201100699

  日期：2012.1.2

  An efficient one‐pot method for the synthesis of various C6‐alkylthio‐substituted purine nucleosides has been developed under microwave irradiation with good to excellent yields without any metal catalyst (see scheme). This process expands the scope of existing synthetic methodologies and was further successfully applied for synthesis of the biologically important compound 4‐nitrobenzylthioinosine

  在微波辐射下，开发了一种高效的一锅法合成各种C6-烷硫基取代的嘌呤核苷的方法，其收率好至极好，而且没有任何金属催化剂（参见方案）。该方法扩大了现有合成方法的范围，并进一步成功地用于生物学上重要的化合物4-硝基苄基硫代肌苷（NBTI）的合成。
• 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。
• 6-Substituted purine 3',5'-cyclic nucleotides
  申请人：ICN Pharmaceuticals, Inc.

  公开号：US03948886A1

  公开（公告）日：1976-04-06

  Described herein are novel 6-alkylthio and 6-arylalkylthio purine 3',5' cyclic nucleotides variously exhibiting adenyl cyclase and (in animal studies) tumor inhibitory properties, interferon potentiation, antiviral activity, and the ability to activate adenosine 3',5'-cyclic phosphate-dependent protein kinase while enjoying resistance to phosphodiesterase hydrolysis superior to that of its naturally occuring analog. The compounds are obtained by alkylation of the corresponding 6-thio nucleotide, which is in turn provided by a novel synthetic route.

  本文介绍了新型的6-烷基硫基和6-芳基烷基硫基嘌呤3'，5'环状核苷酸，它们表现出腺苷酸环化酶和（在动物研究中）抑制肿瘤的特性，干扰素增强作用，抗病毒活性以及激活腺苷酸3'，5'-环磷酸依赖性蛋白激酶的能力，同时具有比其自然存在的类似物更强的磷酸二酯酶水解抵抗力。这些化合物是通过烷基化相应的6-硫代核苷酸获得的，这些核苷酸又是通过一种新的合成路线提供的。
• Alkylation of 6-thiopurine derivatives by the Mitsunobu reaction
  作者：Rafael Dias do Espírito Santo、Bianca Nascimento Monteiro da Silva、Jaime A. Rabi、Vagner D. Pinho

  DOI：10.1080/15257770.2022.2163501

  日期：——

  Abstract Alkylation of thiopurine derivatives with alcohols by the Mitsunobu reaction are reported in moderated to good yields. The method was applied in synthesis of number of thiopurine and thiopurine ribosides derivatives.

  摘要 据报道，通过 Mitsunobu 反应，硫嘌呤衍生物与醇的烷基化反应收率适中。将该方法应用于多种硫嘌呤和硫嘌呤核苷衍生物的合成。