N⁶-(Z)-(4-hydroxy-2-butenyl) adenosine | 113737-39-6

• 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: N⁶-(Z)-(4-hydroxy-2-butenyl) adenosine
• 英文别名: N⁶-(Z)-(4-hydroxy-2-butenyl)adenosine；N6-(Z)-(4-hydroxy-2-butenyl)adenosine；(2R,3R,4S,5R)-2-[6-[[(Z)-4-hydroxybut-2-enyl]amino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol
• CAS: 113737-39-6
• 化学式: C₁₄H₁₉N₅O₅
• 分子量: 337.335
• InChiKey: WZUZYQLEPOOQNF-ZVRKEXNHSA-N

物化性质

• 沸点：
  738.4±70.0 °C(Predicted)
• 密度：
  1.70±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  146
• 氢给体数：
  5
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  6-N-2',3',5'-tri-O-tetraacetyladenosine 在 氨 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 68.0h， 生成 N⁶-(Z)-(4-hydroxy-2-butenyl) adenosine
  参考文献：
  名称：

  N6-substituted adenosines. Cytokinin and antitumor activities

  摘要：

  一系列的N6-腺苷衍生物通过烷基卤化物和醇对N6-乙酰-2'，3'，5'-三-O-乙酰基腺苷（1）进行烷基化合成。结果表明，丙炔基衍生物2a是铜（I）催化的Huisgen [3+2]环加成与叠氮化物反应的良好底物。此点击反应可用于制备1,2,3-三唑基修饰的腺苷库。在两种植物和六种人类癌细胞测试中研究了N6-腺苷的生物活性。发现细胞分裂素和细胞毒性活性之间存在显著的平行关系。同时，最具细胞分裂素活性的化合物3c-3e也被证明是最有效的细胞毒性剂。

  DOI：

  10.1135/cccc2011114

文献信息

• N6-substituted adenosines. Cytokinin and antitumor activities
  作者：Svetlana V. Kolyachkina、Vitali I. Tararov、Cyril S. Alexeev、Dmitry M. Krivosheev、Georgy A. Romanov、Evgenia V. Stepanova、Eliso S. Solomko、Andrey N. Inshakov、Sergey N. Mikhailov

  DOI：10.1135/cccc2011114

  日期：——

  A series of N⁶-adenosine derivatives were synthesized by alkylation of N⁶-acetyl-2′,3′,5′-tri-O-acetyladenosine (1) with alkyl halides and alcohols. It was shown that propargyl derivative 2a is a good substrate for copper(I) catalyzed Huisgen [3+2] cycloaddition with azides. This click-reaction can be used for preparation of the libraries of 1,2,3-triazolyl modified adenosines. Biological activities of N⁶-adenosines were studied in two plant and six human cancer cell assays. The remarkable parallel between cytokinin and cytotoxic activities was found. The most cytokinin active compounds 3c–3e at the same time appeared to be the most potent cytotoxic agents.

  一系列的N6-腺苷衍生物通过烷基卤化物和醇对N6-乙酰-2'，3'，5'-三-O-乙酰基腺苷（1）进行烷基化合成。结果表明，丙炔基衍生物2a是铜（I）催化的Huisgen [3+2]环加成与叠氮化物反应的良好底物。此点击反应可用于制备1,2,3-三唑基修饰的腺苷库。在两种植物和六种人类癌细胞测试中研究了N6-腺苷的生物活性。发现细胞分裂素和细胞毒性活性之间存在显著的平行关系。同时，最具细胞分裂素活性的化合物3c-3e也被证明是最有效的细胞毒性剂。
• New tools in nucleoside toolbox of tick-borne encephalitis virus reproduction inhibitors
  作者：Alexey A. Orlov、Mikhail S. Drenichev、Vladimir E. Oslovsky、Nikolay N. Kurochkin、Pavel N. Solyev、Liubov I. Kozlovskaya、Vladimir A. Palyulin、Galina G. Karganova、Sergey N. Mikhailov、Dmitry I. Osolodkin

  DOI：10.1016/j.bmcl.2017.01.040

  日期：2017.3

  Design and development of nucleoside analogs is an established strategy in the antiviral drug discovery field. Nevertheless, for many viruses the coverage of structure-activity relationships (SAR) in the nucleoside chemical space is not sufficient. Here we present the nucleoside SAR exploration for tick-borne encephalitis virus (TBEV), a member of Flavivirus genus. Promising antiviral activity may be achieved by introduction of large hydrophobic substituents in the position 6 of adenosine or bulky silyl groups to the position 5'. Introduction of methyls to the ribose moiety does not lead to inhibition of TBEV reproduction. Possible mechanisms of action of these nucleosides include the inhibition of viral entry or interaction with TBEV non-structural protein 5 methyltransferase or RNA-dependent RNA polymerase domains. (C) 2017 Elsevier Ltd. All rights reserved.
• STAFFORD, ALLAN E.;CORSE, JOSEPH;LYMAN, MARIAN;METZNER, KURT E., J. CHROMATOGR., 436,(1988) N 1, 93-99
  作者：STAFFORD, ALLAN E.、CORSE, JOSEPH、LYMAN, MARIAN、METZNER, KURT E.

  DOI：——

  日期：——
• Chemical modification of the plant isoprenoid cytokinin N6-isopentenyladenosine yields a selective inhibitor of human enterovirus 71 replication
  作者：Vitali I. Tararov、Aloys Tijsma、Svetlana V. Kolyachkina、Vladimir E. Oslovsky、Johan Neyts、Mikhail S. Drenichev、Pieter Leyssen、Sergey N. Mikhailov

  DOI：10.1016/j.ejmech.2014.11.048

  日期：2015.1

  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.