6-amino-9-<(propargyloxy)methyl>purine | 139758-64-8

• 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: 6-amino-9-<(propargyloxy)methyl>purine
• 英文别名: 1-(propargyloxymethyl)adenine；9-(propargyloxymethyl)adenine；6-Amino-9-(propargyloxymethyl)purine；9-(prop-2-ynoxymethyl)purin-6-amine
• CAS: 139758-64-8
• 化学式: C₉H₉N₅O
• 分子量: 203.203
• InChiKey: OOONYYIOODBIQY-UHFFFAOYSA-N

物化性质

• 沸点：
  455.5±55.0 °C(Predicted)
• 密度：
  1.37±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  78.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-amino-9-<(propargyloxy)methyl>purine 在 N-氯代丁二酰亚胺 、 偶氮二异丁腈 、 三正丁基氢锡 、 sodium iodide 、 sodium nitrite 作用下， 以 溶剂黄146 为溶剂， 反应 18.33h， 生成 9-<<<(Z)-5-iodo-5-propenyl>oxy>methyl>hypoxanthine
  参考文献：
  名称：

  Synthesis and biological studies of unsaturated acyclonucleoside analogs of S-adenosyl-L-homocysteine hydrolase inhibitors

  摘要：

  The design, synthesis, and biological evaluation of several unsaturated acyclonucleosides related to augustmycin A are described. The (propargyloxy)methyl acyclonucleoside analogues of 6-chloropurine, adenine, 6-methoxypurine, hypoxanthine, 6-mercaptopurine, and azathioprine have been prepared. The 9-[(propargyloxy)methyl]adenine (5) and 9-[(propargyloxy)methyl]hypoxanthine (12) analogues were converted to the corresponding 5'-tributylstannyl intermediates (9 and 13), respectively, which gave 9-[[[(Z)-5-iodo-5-propenyl]oxy]methyl]adenine (10) and 9-[[[(Z)-5-iodo-5-propenyl]oxy]methyl]hypoxanthine (14), respectively, after iododestannylation. The [I-125]-radiolabeled congeners of 10 and 14 were prepared as potential metabolic markers. Among the unsaturated acyclonucleosides tested, 9-[(propargyloxy)methyl]-6-chloropurine (3), 9-[(propargyloxy)methyl]-6-mercaptopurine (15), 9-[(proparglyoxy)methyl]azathioprine (17), and angustmycin A analogue 10 showed inhibition of cancer cell growth, but only at a minimal level, and 17 also showed 14% cancer cel death in vitro. Compound 10 provided approximately 50% protection against HIV at 10(-4) M concentrations. Biodistribution results of [I-125]-10 in mice indicate that compound 10 is readily metabolized via deiodination in vivo, possibly by serving as a substrate for the enzyme S-adenosyl-L-homocysteine hydrolase.

  DOI：

  10.1021/jm00086a012
• 作为产物：
  描述：

  N,N-dimethyl-N'-(9-((prop-2-yn-1-yloxy)methyl)-9H-purin-6-yl)formimidamide 在 氨 作用下， 以 甲醇 为溶剂， 反应 26.0h， 以40 mg的产率得到6-amino-9-<(propargyloxy)methyl>purine
  参考文献：
  名称：

  截短侧耳素衍生物的点击化学方法，第2部分：与无环核苷的缀合物及其核糖体结合和抗菌活性

  摘要：

  截短侧耳素是一种与细菌核糖体结合并因此抑制蛋白质合成的抗生素。通过点击化学策略合成了一系列新的半合成截短侧耳素衍生物。截短侧耳素通过不同的接头缀合至核碱基，核苷或苯基，作为截短侧耳素C22位置的侧链延伸。接头的设计是基于我们第一个截短侧耳素衍生物系列的最佳接头后进行的，即构象限制或等位亚甲基向氧的交换。新化合物与大肠杆菌的结合通过分子建模和核苷酸U2506的化学足迹研究了核糖体，发现所有衍生物都结合到特定位点，并且大多数比截短侧耳素本身更好。还通过核苷酸U2585的化学足迹探索了侧链延伸的作用，结果表明所有化合物都在不同程度上与该位置相互作用。具有接头构象限制的衍生物通常比具有接头中碳原子之一与亲水性氧等位交换的衍生物具有更高的亲和力。用三种不同细菌菌株进行的生长抑制试验显示出几种新化合物的显着活性。

  DOI：

  10.1021/jm201266b

文献信息

• Synthesis and antiviral activity of propargyl-hydroxymethyl derivatives of uracil and adenine
  作者：A. A. Ozerov、A. K. Brel、E. I. Boreko、G. V. Vladyko、L. V. Korobchenko

  DOI：10.1007/bf02219308

  日期：1994.10

  herpesviruses [10]. In the present work, the synthesis and antiviral activity of acetylene analogs of compounds previously obtained by us is described. The synthesis of 1-(propargyloxymethyl) derivatives of uracil (I-VI) and 9-(propargyloxymethyl)adenine (VII) was carried out by alkylating trimethylsilyl derivatives of uracil and the potassium salt of adenine with propargyloxymethyl chloride, obtained

  乙炔核苷酸衍生物，在分子的杂环碱基、核糖基环或非环部分的不同位置含有具有碳-碳三键的片段，可用作抗病毒和抗肿瘤剂 [1, 2]，并作为获得其他生物活性物质 [3-9]。我们之前已经确定尿嘧啶的一些烯丙氧基甲基衍生物对疱疹病毒具有明显的抑制活性 [10]。在目前的工作中，描述了我们以前获得的化合物的乙炔类似物的合成和抗病毒活性。尿嘧啶 (I-VI) 和 9-(炔丙氧基甲基) 腺嘌呤 (VII) 的 1-(炔丙氧基甲基) 衍生物的合成是通过用炔丙氧基甲基氯烷基化尿嘧啶的三甲基甲硅烷基衍生物和腺嘌呤的钾盐来进行的，
• Synthesis of unsaturated adenine derivatives, potential inhibitors of S-adenosyl-L-homocysteine hydrolase
  作者：A. A. Ozerov、M. S. Novikov

  DOI：10.1007/bf01164872

  日期：1996.6
• A Click Chemistry Approach to Pleuromutilin Derivatives, Part 2: Conjugates with Acyclic Nucleosides and Their Ribosomal Binding and Antibacterial Activity
  作者：Ida Dreier、Surender Kumar、Helle Søndergaard、Maria Louise Rasmussen、Lykke Haastrup Hansen、Nanna Holmgaard List、Jacob Kongsted、Birte Vester、Poul Nielsen

  DOI：10.1021/jm201266b

  日期：2012.3.8

  inhibit protein synthesis. A new series of semisynthetic pleuromutilin derivatives were synthesized by a click chemistry strategy. Pleuromutilin was conjugated by different linkers to a nucleobase, nucleoside, or phenyl group, as a side-chain extension at the C22 position of pleuromutilin. The linkers were designed on the basis of the best linker from our first series of pleuromutilin derivatives following

  截短侧耳素是一种与细菌核糖体结合并因此抑制蛋白质合成的抗生素。通过点击化学策略合成了一系列新的半合成截短侧耳素衍生物。截短侧耳素通过不同的接头缀合至核碱基，核苷或苯基，作为截短侧耳素C22位置的侧链延伸。接头的设计是基于我们第一个截短侧耳素衍生物系列的最佳接头后进行的，即构象限制或等位亚甲基向氧的交换。新化合物与大肠杆菌的结合通过分子建模和核苷酸U2506的化学足迹研究了核糖体，发现所有衍生物都结合到特定位点，并且大多数比截短侧耳素本身更好。还通过核苷酸U2585的化学足迹探索了侧链延伸的作用，结果表明所有化合物都在不同程度上与该位置相互作用。具有接头构象限制的衍生物通常比具有接头中碳原子之一与亲水性氧等位交换的衍生物具有更高的亲和力。用三种不同细菌菌株进行的生长抑制试验显示出几种新化合物的显着活性。
• Synthesis and biological studies of unsaturated acyclonucleoside analogs of S-adenosyl-L-homocysteine hydrolase inhibitors
  作者：Ahmad Hasan、Prem C. Srivastava

  DOI：10.1021/jm00086a012

  日期：1992.4

  The design, synthesis, and biological evaluation of several unsaturated acyclonucleosides related to augustmycin A are described. The (propargyloxy)methyl acyclonucleoside analogues of 6-chloropurine, adenine, 6-methoxypurine, hypoxanthine, 6-mercaptopurine, and azathioprine have been prepared. The 9-[(propargyloxy)methyl]adenine (5) and 9-[(propargyloxy)methyl]hypoxanthine (12) analogues were converted to the corresponding 5'-tributylstannyl intermediates (9 and 13), respectively, which gave 9-[[[(Z)-5-iodo-5-propenyl]oxy]methyl]adenine (10) and 9-[[[(Z)-5-iodo-5-propenyl]oxy]methyl]hypoxanthine (14), respectively, after iododestannylation. The [I-125]-radiolabeled congeners of 10 and 14 were prepared as potential metabolic markers. Among the unsaturated acyclonucleosides tested, 9-[(propargyloxy)methyl]-6-chloropurine (3), 9-[(propargyloxy)methyl]-6-mercaptopurine (15), 9-[(proparglyoxy)methyl]azathioprine (17), and angustmycin A analogue 10 showed inhibition of cancer cell growth, but only at a minimal level, and 17 also showed 14% cancer cel death in vitro. Compound 10 provided approximately 50% protection against HIV at 10(-4) M concentrations. Biodistribution results of [I-125]-10 in mice indicate that compound 10 is readily metabolized via deiodination in vivo, possibly by serving as a substrate for the enzyme S-adenosyl-L-homocysteine hydrolase.