6-(2-Thienyl)-9-(β-D-ribofuranosyl)purine

• 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-(2-Thienyl)-9-(β-D-ribofuranosyl)purine
• 英文别名: 9-(β-D-ribofuranosyl)-6-(2-thienyl)-9H-purine；FP16；5-(Hydroxymethyl)-2-(6-(2-thienyl)purin-9-yl)oxolane-3,4-diol；(2R,3S,4R,5R)-2-(hydroxymethyl)-5-(6-thiophen-2-ylpurin-9-yl)oxolane-3,4-diol
• 化学式: C₁₄H₁₄N₄O₄S
• 分子量: 334.356
• InChiKey: JJGFWBKSCRSUKK-UBPLGANQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  142
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  肌苷 在 吡啶 、 四(三苯基膦)钯 、 sodium methylate 、 potassium carbonate 、 三乙胺 、 三氯氧磷 作用下， 以 甲醇 、 甲苯 为溶剂， 140.0 ℃ 、689.49 kPa 条件下， 反应 16.6h， 生成 6-(2-Thienyl)-9-(β-D-ribofuranosyl)purine
  参考文献：
  名称：

  类异戊二烯衍生物N6-苄基腺苷CM223通过甲羟戊酸途径在神经胶质瘤患者来源的原代细胞中发挥抗肿瘤作用。

  摘要：

  背景和目的N6-异戊烯基腺苷（i6A）是一种修饰的核苷，具有体外和体内的抗增殖作用。我们先前证明i6A的作用与法呢基焦磷酸合酶（FPPS）的表达和活性相关，法呢基焦磷酸合酶（FPPS）是参与甲羟戊酸（MVA）途径的关键酶，在脑癌中异常。为了开发新的抗神经胶质瘤策略，我们测试了比i6A表现出更大活性的相关化合物。实验方法我们设计并合成了i6A衍生物，其特征是在腺苷的N6位置引入了不同的化学部分，并测试了它们在源自患者的U87细胞和原代神经胶质瘤培养物中的功效。基于NMR的结构分析，分子对接计算和siRNA介导的敲低被用来阐明其针对FPPS蛋白的作用的分子基础。关键结果CM223是一种i6A衍生物，在腺嘌呤的N6位包含一个苄基部分，在选择性靶向神经胶质瘤细胞而非正常人星形胶质细胞中表现出明显的活性。这是由于诱导细胞凋亡的内在途径和抑制增殖，以及对FPPS依赖性蛋白异戊二烯的阻断，从而抵消了EG

  DOI：

  10.1111/bph.13824

文献信息

• Cytostatic 6-Arylpurine Nucleosides III. Synthesis and Structure-Activity Relationship Study in Cytostatic Activity of 6-Aryl-, 6-Hetaryl- and 6-Benzylpurine Ribonucleosides
  作者：Michal Hocek、Antonín Holý、Ivan Votruba、Hana Dvořáková

  DOI：10.1135/cccc20010483

  日期：——

  A series of fifteen 6-aryl-, 6-hetaryl- and 6-benzylpurine ribonucleosides has been prepared by Pd-catalyzed cross-coupling reactions of 6-chloro-9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)- purine with arylboronic acids, hetarylzinc halides, hetarylstannanes or benzylzinc halides followed by deprotection. Structure-activity relationship study revealed that besides 6-(4-substituted phenyl)purine nucleosides, also some 6-hetaryl- and 6-benzylpurine ribonucleosides possess considerable cytostatic activity.

  一系列十五种6-芳基、6-杂芳基和6-苄基嘌呤核苷已通过Pd催化的交叉偶联反应制备，该反应是以6-氯-9-(2,3,5-三-O-乙酰基-β-D-核糖呋喃基)-嘌呤与芳基硼酸、杂芳基锌卤化物、杂芳基锡烷或苄基锌卤化物反应后进行去保护。结构活性关系研究表明，除了6-(4-取代苯基)嘌呤核苷外，一些6-杂芳基和6-苄基嘌呤核苷也具有相当的抗细胞增殖活性。
• Cytostatic evaluations of nucleoside analogs related to unnatural base pairs for a genetic expansion system
  作者：Michiko Kimoto、Kei Moriyama、Shigeyuki Yokoyama、Ichiro Hirao

  DOI：10.1016/j.bmcl.2007.07.088

  日期：2007.10

  nucleoside analogs by an MTT assay. Several nucleoside analogs based on two types of unnatural base pairs were tested. One is a hydrogen-bonded base pair between 2-amino-6-(2-thienyl)purine (s) and pyridin-2-one (y), and the other is a hydrophobic base pair between 7-(2-thienyl)imidazo[4,5-b]pyridine (Ds) and pyrrole-2-carbaldehyde (Pa). Among the nucleoside analogs, the ribonucleoside of 6-(2-thienyl)purine

  将非天然碱基对引入DNA可以扩展遗传信息。为了将非天然碱基对应用于体内系统，我们通过MTT分析评估了几种核苷类似物的细胞抑制毒性。测试了基于两种非天然碱基对的几种核苷类似物。一个是2-氨基-6-（2-噻吩基）嘌呤和吡啶-2-酮（y）之间的氢键碱基对，另一个是7-（2-噻吩基）之间的疏水碱基对。咪唑并[4,5-b]吡啶（Ds）和吡咯-2-甲醛（Pa）。在核苷类似物中，6-（2-噻吩基）嘌呤的核糖核苷对CCRF-CEM（尤其是HT-1080）以及正常的成纤维细胞系WI-38具有最高的细胞抑制活性。其他类似物，包括其2'-脱氧，2-氨基和1-脱氮嘌呤核苷衍生物，它们对CCRF-CEM和HT-1080的活性较低，并且这些核苷对WI-38的毒性较低。y和Pa的核苷对CCRF-CEM，HT-1080和WI-38没有活性。另外，s和y或Ds和Pa的配对核苷的组合未观察到细胞抑制协同作用。
• Synthesis and evaluation of the substrate activity of C-6 substituted purine ribosides with E. coli purine nucleoside phosphorylase: Palladium mediated cross-coupling of organozinc halides with 6-chloropurine nucleosides
  作者：Abdalla E.A. Hassan、Reham A.I. Abou-Elkhair、James M. Riordan、Paula W. Allan、William B. Parker、Rashmi Khare、William R. Waud、John A. Montgomery、John A. Secrist

  DOI：10.1016/j.ejmech.2011.10.039

  日期：2012.1

  A series of C-6 alkyl, cycloalkyl, and aryl-9-(beta-D-ribofuranosyl)purines were synthesized and their substrate activities with Escherichia colt purine nucleoside phosphorylase (E. coli PNP) were evaluated. (Ph3P)(4)Pd-mediated cross-coupling reactions of 6-chloro-9-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)-purine (6) with primary alkyl (Me, Et, n-Pr, n-Bu, isoBu) zinc halides followed by treatment with NH3/MeOH gave the corresponding 6-alkyl-9-(beta-D-ribofuranosyl)purine derivatives 7-11, respectively, in good yields. Reactions of 6 with cycloalkyl(propyl, butyl, pentyl)zinc halides and aryl (phenyl, 2-thienyl)zinc halides gave under similar conditions the corresponding 6-cyclopropyl, cyclobutyl, cyclopentyl, phenyl, and thienyl -9-(beta-D-ribofuranosyl)purine derivatives 12-16, respectively in high yields. E. colt PNP showed a high tolerance to the steric and hydrophobic environment at the 6-position of the synthesized purine ribonucleosides. Significant cytotoxic activity was observed for 8, 12, 15, and 16. Evaluation of 12 and 16 against human tumor xenografts in mice did not demonstrate any selective antitumor activity. In addition, 6-methyl-9-(beta-D-arabinofuranosyl)purine (18) was prepared and evaluated. (C) 2011 Elsevier Masson SAS. All rights reserved.
• Synthesis and Antimycobacterial Activity of 6-Arylpurines:  The Requirements for the <i>N</i>-9 Substituent in Active Antimycobacterial Purines
  作者：Lise-Lotte Gundersen、Jon Nissen-Meyer、Bjørn Spilsberg

  DOI：10.1021/jm0110284

  日期：2002.3.1

  6-Arylpurines carrying a variety of substituents in the 9-position were prepared by Stille coupling between appropriately substituted 6-chloropurines and aryl(tributyl)tin, and the compounds were screened for antibacterial activity against Mycobacterium tuberculosis H-37-Rv. The lowest minimum inhibitory concentration value, 0.78 mug/mL, was found for 9-benzyl-2-chloro-6-(2-furyl)purine. This compound exhibited relatively low cytotoxicity, and it was active against several singly drug-resistant strains of M. tuberculosis.
• The isoprenoid derivative N⁶-benzyladenosine CM223 exerts antitumor effects in glioma patient-derived primary cells through the mevalonate pathway
  作者：Elena Ciaglia、Manuela Grimaldi、Mario Abate、Mario Scrima、Manuela Rodriquez、Chiara Laezza、Roberta Ranieri、Simona Pisanti、Pierangela Ciuffreda、Clementina Manera、Patrizia Gazzerro、Anna Maria D'Ursi、Maurizio Bifulco

  DOI：10.1111/bph.13824

  日期：2017.7

  inhibition of proliferation, along with blockade of FPPS-dependent protein prenylation, which counteracted oncogenic signalling mediated by EGF receptors. CONCLUSION AND IMPLICATIONS The biological effects together with structural data on interaction of CM223 with FPPS, provided additional evidence for the correlation of the i6A/CM223 antitumor activity with FPPS modulation. Because the MVA pathway is an important

  背景和目的N6-异戊烯基腺苷（i6A）是一种修饰的核苷，具有体外和体内的抗增殖作用。我们先前证明i6A的作用与法呢基焦磷酸合酶（FPPS）的表达和活性相关，法呢基焦磷酸合酶（FPPS）是参与甲羟戊酸（MVA）途径的关键酶，在脑癌中异常。为了开发新的抗神经胶质瘤策略，我们测试了比i6A表现出更大活性的相关化合物。实验方法我们设计并合成了i6A衍生物，其特征是在腺苷的N6位置引入了不同的化学部分，并测试了它们在源自患者的U87细胞和原代神经胶质瘤培养物中的功效。基于NMR的结构分析，分子对接计算和siRNA介导的敲低被用来阐明其针对FPPS蛋白的作用的分子基础。关键结果CM223是一种i6A衍生物，在腺嘌呤的N6位包含一个苄基部分，在选择性靶向神经胶质瘤细胞而非正常人星形胶质细胞中表现出明显的活性。这是由于诱导细胞凋亡的内在途径和抑制增殖，以及对FPPS依赖性蛋白异戊二烯的阻断，从而抵消了EG