N-烯丙基腺苷 | 15763-12-9

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 中文名称: N-烯丙基腺苷
• 英文名称: 6-N-allyladenosine
• 英文别名: N6-Allyladenosine；N-Allyladenosine；(2R,3S,4R,5R)-2-(hydroxymethyl)-5-[6-(prop-2-enylamino)purin-9-yl]oxolane-3,4-diol
• CAS: 15763-12-9
• 化学式: C₁₃H₁₇N₅O₄
• 分子量: 307.309
• InChiKey: WTYYPLSFICPDGL-QYVSTXNMSA-N

物化性质

• 熔点：
  165-167 °C
• 沸点：
  646.2±65.0 °C(Predicted)
• 密度：
  1.67±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  126
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N-烯丙基腺苷 在 盐酸 作用下， 以 水 为溶剂， 反应 8.0h， 以70%的产率得到N-烯丙基-N-(9H-嘌呤-6-基)胺
  参考文献：
  名称：

  Chemical modification of the plant isoprenoid cytokinin N6-isopentenyladenosine yields a selective inhibitor of human enterovirus 71 replication

  摘要：

  In this study, we demonstrate that N-6-isopentenyladenosine, which essentially is a plant cytokinin-like compound, exerts a potent and selective antiviral effect on the replication of human enterovirus 71 with an EC50 of 1.0 +/- 0.2 mu M and a selectivity index (SI) of 5.7. The synthesis of analogs with modification of the N-6-position did not result in a lower EC50 value. However, in particular with the synthesis of N6-(5hexene-2-yne-1-yl)adenosine (EC50 = 43 +/- 1.5 mu M), the selectivity index was significantly increased: because of a reduction in the adverse effect of this compound on the host cells, an SI > 101 could be calculated. With this study, we for the first time provide proof that a compound class that is based on the plant cytokinin skeleton offers an interesting starting point for the development of novel antivirals against mammalian viruses, in the present context in particular against enterovirus 71. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.11.048
• 作为产物：
  描述：

  6-N-2',3',5'-tri-O-tetraacetyladenosine 在 氨 、 potassium carbonate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 68.0h， 生成 N-烯丙基腺苷
  参考文献：
  名称：

  Chemical modification of the plant isoprenoid cytokinin N6-isopentenyladenosine yields a selective inhibitor of human enterovirus 71 replication

  摘要：

  In this study, we demonstrate that N-6-isopentenyladenosine, which essentially is a plant cytokinin-like compound, exerts a potent and selective antiviral effect on the replication of human enterovirus 71 with an EC50 of 1.0 +/- 0.2 mu M and a selectivity index (SI) of 5.7. The synthesis of analogs with modification of the N-6-position did not result in a lower EC50 value. However, in particular with the synthesis of N6-(5hexene-2-yne-1-yl)adenosine (EC50 = 43 +/- 1.5 mu M), the selectivity index was significantly increased: because of a reduction in the adverse effect of this compound on the host cells, an SI > 101 could be calculated. With this study, we for the first time provide proof that a compound class that is based on the plant cytokinin skeleton offers an interesting starting point for the development of novel antivirals against mammalian viruses, in the present context in particular against enterovirus 71. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.11.048

文献信息

• Synthesis and Structure–Activity Relationship Investigation of Adenosine-Containing Inhibitors of Histone Methyltransferase DOT1L
  作者：Justin L. Anglin、Lisheng Deng、Yuan Yao、Guobin Cai、Zhen Liu、Hong Jiang、Gang Cheng、Pinhong Chen、Shuo Dong、Yongcheng Song

  DOI：10.1021/jm300917h

  日期：2012.9.27

  Histone3-lysine79 (H3K79) methyltransferase DOT1L has been found to be a drug target for acute leukemia with MLL (mixed lineage leukemia) gene translocations. A total of 55 adenosine-containing compounds were designed and synthesized, among which several potent DOT1L inhibitors were identified with Ki values as low as 0.5 nM. These compounds also show high selectivity (>4500-fold) over three other histone methyltransferases

  组蛋白 3-赖氨酸 79 (H3K79) 甲基转移酶 DOT1L 已被发现是具有 MLL（混合谱系白血病）基因易位的急性白血病的药物靶点。总共设计和合成了 55 种含腺苷的化合物，其中鉴定了几种有效的 DOT1L 抑制剂，K i值低至 0.5 nM。与其他三种组蛋白甲基转移酶相比，这些化合物还显示出高选择性（> 4500 倍）。讨论了这些化合物对 DOT1L 的抑制活性的构效关系 (SAR)。强效 DOT1L 抑制剂对 MLL 易位白血病细胞系 MV4;11 和 THP1 的增殖具有选择性活性，EC 504–11 μM 的值。等温滴定量热研究表明，两种代表性抑制剂以高亲和力与 DOT1L:核小体复合物结合，仅与酶辅因子 SAM（S-腺苷-1-甲硫氨酸）竞争，而不与底物核小体竞争。
• 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。
• N6-Alkyladenosines: Synthesis and evaluation of in vitro anticancer activity
  作者：Roberta Ottria、Silvana Casati、Erika Baldoli、Jeanette A.M. Maier、Pierangela Ciuffreda

  DOI：10.1016/j.bmc.2010.09.030

  日期：2010.12

  between structure and biological activity of iPA. The structures of the compounds were confirmed by standard studies of 1H NMR, MS and elemental analysis. These molecules were then evaluated for their anti-proliferative activity on bladder cancer cells. We found that some of these compounds possess anti-proliferative activity but have no effect on cell invasion and metalloprotease activity.

  合成了一系列在N 6位上不同取代的腺苷类似物，以继续我们对iPA的结构与生物学活性之间关系的研究。化合物的结构通过1 H NMR，MS和元素分析的标准研究确认。然后评估这些分子对膀胱癌细胞的抗增殖活性。我们发现其中一些化合物具有抗增殖活性，但对细胞侵袭和金属蛋白酶活性没有影响。
• N6-isopentenyladenosine a new potential anti-angiogenic compound that targets human microvascular endothelial cells <i>in vitro</i>
  作者：Sara Castiglioni、Valentina Romeo、Silvana Casati、Roberta Ottria、Cristiana Perrotta、Pierangela Ciuffreda、Jeanette A. M. Maier

  DOI：10.1080/15257770.2018.1503673

  日期：2018.10.3

  significant reduction of cell viability, upregulated p21 and promoted caspase-3 cleavage in a dose dependent manner leading to apoptotic cell death as detected by FACS analysis. To understand structure-function relationship of N6-isopentenyladenosine, we investigated the effect of some N6-isopentenyladenosine analogs. Our results suggest that N6-isopentenyladenosine and some of its derivatives are potentially

  摘要 N6-异戊烯基腺苷是一种对正常细胞和肿瘤细胞具有抗增殖和促凋亡作用的非典型核苷。考虑到血管生成在各种疾病中的作用，我们研究了 N6-异戊烯基腺苷对人微血管内皮细胞（血管生成的主角）的细胞毒作用。我们的结果表明，N6-异戊烯基腺苷以剂量依赖性方式诱导细胞活力的显着降低，上调 p21 并促进 caspase-3 切割，导致 FACS 分析检测到的细胞凋亡。为了了解 N6-异戊烯基腺苷的结构-功能关系，我们研究了一些 N6-异戊烯基腺苷类似物的作用。
• Some short-chain N6-substituted adenosine analogs with antitumor properties
  作者：M. H. Fleysher、R. J. Bernacki、G. A. Bullard

  DOI：10.1021/jm00186a031

  日期：1980.12

  spans of mice bearing mammary carcinoma were obtained by treatment with the N6-allyl, N6-isopropyl, and N6-propargyl analogues, respectively. In rats, the N6-allyl analogue slowed the rate of transplantable mammary tumor growth by one-fourth. The short-chain adenosine analogues are more active in the treatment of animal carcinomas than in the leukemia or sarcoma tumor cell systems.

  化合物N6-烯丙基-，N6-异丙基-，N6-炔丙基-和N6-（2-甲基烯丙基）腺苷是通过使6-氯嘌呤核糖核苷与过量的相应胺在乙醇中，在两种酸存在下反应制备的受体几乎产生定量的产量。该化合物在许多体外和体内肿瘤细胞系统中均显示出生物学活性。通过分别用N6-烯丙基，N6-异丙基和N6-炔丙基类似物处理，可以使荷瘤小鼠的寿命大大提高。在大鼠中，N6-烯丙基类似物使可移植乳腺肿瘤的生长速度减慢了四分之一。短链腺苷类似物在治疗动物癌中比在白血病或肉瘤肿瘤细胞系统中更活跃。