9-<2,5-bis-O-(tert-butyldimethylsilyl)-β-D-arabinofuranosyl>adenine | 82845-91-8

• 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: 9-<2,5-bis-O-(tert-butyldimethylsilyl)-β-D-arabinofuranosyl>adenine
• 英文别名: TBDMS(-2)[TBDMS(-5)]D-Araf(b)-adenin-9-yl；(2R,3R,4S,5R)-5-(6-aminopurin-9-yl)-4-[tert-butyl(dimethyl)silyl]oxy-2-[[tert-butyl(dimethyl)silyl]oxymethyl]oxolan-3-ol
• CAS: 82845-91-8
• 化学式: C₂₂H₄₁N₅O₄Si₂
• 分子量: 495.77
• InChiKey: XERXHSJOIUTEBZ-DFYYWFRZSA-N

物化性质

• 沸点：
  572.0±60.0 °C(Predicted)
• 密度：
  1.18±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.08
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  118
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  9-<2,5-bis-O-(tert-butyldimethylsilyl)-β-D-arabinofuranosyl>adenine 在 吡啶 、 四丁基氟化铵 作用下， 以 四氢呋喃 、 溶剂黄146 为溶剂， 反应 48.0h， 生成 9-<3-O-acetyl-β-D-arabinofuranosyl>adenine
  参考文献：
  名称：

  9-β-d-阿拉伯呋喃糖基腺嘌呤前药中水解和溶剂依赖性2'→5'和3'→5'酰基迁移

  摘要：

  作为进一步进行定量体内研究的先决条件，以进一步探索9-β-D-阿拉伯呋喃糖基腺嘌呤（ara-A）的2'，3'-二-O-乙酰基衍生物对疱疹病毒感染的动力学活性研究了2'，3'-二-O-乙酰基衍生物以及2'-，3'-和5'-单乙酸酯的溶液降解。基于对取代基效应的考虑，发现水溶液水解的速率与等级排序预测一致。然而，初步的体内水解数据与这种预测无关，这表明需要对分子结构对酶催化水解的影响进行更系统的研究。2'-3'-二酯和3'-单酯在水溶液中的重要反应，除了酯水解外，还有3'。---- 5'的酰基迁移。乙腈中的研究证实，2'---- 5'酰基迁移不会在水中发生，而是在有机溶剂中的主要迁移途径。1 H NMR光谱用于研究糖环的构象对溶剂环境的依赖性。尽管确实发生了C（2'）内基和C（3'）内基构象状态之间的平衡变化，但这不是一个戏剧性的变化，不能解释在酰基迁移动力学中观察到的溶剂选择性。

  DOI：

  10.1002/jps.2600740805
• 作为产物：
  描述：

  叔丁基二甲基氯硅烷 、 阿糖腺苷 在 三乙烯二胺 、 AgNO₃ 作用下， 以 四氢呋喃 为溶剂， 以60%的产率得到9-<2,5-bis-O-(tert-butyldimethylsilyl)-β-D-arabinofuranosyl>adenine
  参考文献：
  名称：

  N（6）-，5'，3'-O-和5'，2'-O取代的腺嘌呤核苷类似物的设计，合成和抗黄病毒活性。

  摘要：

  在对代表性核苷类似物文库的随机筛选中，我们发现腺嘌呤衍生物FEVB28和FEG118是黄病毒科抑制剂，具有与利巴韦林相当的效力，甚至更高。这些研究促使我们设计了本文所报道的新型受保护的核苷类似物，其在基于细胞的测定中显示出有趣的抗牛病毒性腹泻病毒（BVDV）活性和低细胞毒性（4，23，29 EC（50）：14分别为11、26 microM，CC（50）> 100 microM）和针对BVDV的RNA依赖性RNA聚合酶（RdRp）的酶分析中的显着活性（分别为4、23、29，RdRp抑制活性27、16、15 microM） 。

  DOI：

  10.1248/cpb.56.423

文献信息

• MODULATOR OF ACTIVITY OF ADENYLATE CYCLASE
  申请人：Ishikawa Yoshihiro

  公开号：US20130261073A1

  公开（公告）日：2013-10-03

  The present invention provides a novel compound capable of inhibiting cardiac adenylyl cyclase. The present invention relates to a compound represented by the following formula (I) or a pharmaceutically acceptable salt, ester or solvate thereof: where R 1 , R 2 and R 3 each independently represent a hydrogen atom or an acyl group having an acidic or basic substituent, provided that all of R 1 , R 2 and R 3 are not simultaneously a hydrogen atom. The present invention also provides a modulator of adenylyl cyclase activity, a pharmaceutical composition and a food composition, all of which comprise the above-described compound or a pharmaceutically acceptable salt, ester or solvate thereof.

  本发明提供了一种新型化合物，能够抑制心脏腺苷酸环化酶。本发明涉及以下式（I）表示的化合物或其药学上可接受的盐、酯或溶剂：其中R1、R2和R3分别独立地表示氢原子或具有酸性或碱性取代基的酰基，前提是R1、R2和R3中的所有原子不同时为氢原子。本发明还提供了腺苷酸环化酶活性调节剂、制药组合物和食品组合物，所有这些都包括上述化合物或其药学上可接受的盐、酯或溶剂。
• Synthesis and evaluation of a series of 2'-O-acyl derivatives of 9-.beta.-D-arabinofuranosyladenine as antiherpes agents
  作者：David C. Baker、S. D. Kumar、William J. Waites、Gussie Arnett、William M. Shannon、William I. Higuchi、W. J. Lambert

  DOI：10.1021/jm00369a007

  日期：1984.3

  A series of four 9-(2-O-acyl-beta-D-arabinofuranosyl)adenines (5a-d) was synthesized by acylation of 9-[3,5-bis-O-(tert-butyldimethylsilyl)-beta-D-arabinofuranosyl]adenine (2), followed by removal of the tert-butyldimethylsilyl groups under conditions (HOAc, tetra-n-butylammonium fluoride) that prevented acyl migration. The four 2'-O-acyl derivatives 5a-d showed activity in vitro against herpes type 1 viruses [virus ratings = 1.5-2.6; MIC50 = 26-72 micrograms/mL (8.48-21.3 X 10(-5) M)]. The 2'-O-acetyl (5a) and 2'-O-valeryl (5d) derivatives were evaluated in a guinea pig model for genital herpes (herpes type 2); only 5a showed potent activity when given 6 or 24 h postinfection.
• Ogilvie, Kelvin K.; McGee, Danny P. C.; Boisvert, Suzanne M., Canadian Journal of Chemistry, 1983, vol. 61, p. 1204 - 1212
  作者：Ogilvie, Kelvin K.、McGee, Danny P. C.、Boisvert, Suzanne M.、Hakimelahi, Gholam H.、Proba, Zbigniew A.

  DOI：——

  日期：——
• Silylated derivatives of arabinonucleosides
  作者：Kelvin K. Ogilvie、Gholam H. Hakimelahi、Zbigniew A. Proba、Danny P.C. McGee

  DOI：10.1016/s0040-4039(00)87243-3

  日期：1982.1
• Design, Synthesis, and Structure-Activity Relationship of Novel Dinucleotide Analogs as Agents against Herpes and Human Immunodeficiency Viruses
  作者：Gholam H. Hakimelahi、Ali A. Moosavi-Movahedi、Majid M. Sadeghi、Shwu-Chen Tsay、Jih Ru Hwu

  DOI：10.1021/jm00023a004

  日期：1995.11

  A new acyclic nucleoside phosphonate (13) containing an adenine moiety was synthesized, which acted as an excellent inhibitor of calf mucosal adenosine deaminase. This inhibitory property allows it to exert great synergistic effect on certain antiviral agents (e.g., ara-A, 37). Phosphonate 13 was not phosphorylated by the bovine brain guanylate kinase nor by 5-phosphoribosyl 1-pyrophosphate synthetase. Syntheses of biologically active nucleotide phosphonate 40 and its phosphonoamidate derivative 42 were accomplished, which showed remarkable activity against herpes viruses and exhibited low host cell toxicity. 3'-Azido-nucleoside phosphonate 20 and 3'-fluoronucleoside phosphonate 32, as well as the corresponding dinucleotide analogs 47 and 48, and their respective phosphonoamidates 53-56 were also synthesized as new compounds, among which phosphonoamidates 53-56 showed potent activity against human immunodeficiency virus. Phosphonoamidates 55 and 56 bearing a methyl D-alaninate moiety exhibited less cellular toxicity than 53 and 54 bearing a methyl L-alaninate moiety. Nucleotide phosphonate 40 as well as dinucleotide phosphonates 47 and 48 were found susceptible to degradation by phosphodiesterases. Their respective phosphonoamidates 42 and 53-56, however, were completely resistant to snake venom and spleen enzymes.