2-fluoro-9-trimethylsilyladenine | 153997-66-1

• 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: 2-fluoro-9-trimethylsilyladenine
• 英文别名: 2-fluoro-9-trimethylsilylpurin-6-amine
• CAS: 153997-66-1
• 化学式: C₈H₁₂FN₅Si
• 分子量: 225.301
• InChiKey: CBXMACSSMWMOAR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.23
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  69.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-fluoro-9-trimethylsilyladenine 在 吡啶 、 四丁基氟化铵 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 26.5h， 生成 3'-[(2-cyanoethyl)diisopropylphosphoramidite]-O^5'-dimethoxytrityl-N⁶-(N',N'-di-n-butylformamidine) 2-fluorodeoxyadenosine
  参考文献：
  名称：

  Characterization of 2‐Fluoro‐2’‐deoxyadenosine in Duplex, G‐Quadruplex and i‐Motif

  摘要：

  AbstractAmong various kinds of fluorine‐substituted biomolecules, 2‐fluoroadenine (2FA) and its derivatives have been actively investigated as therapeutic reagents, radio‐sensitizers, and 19F NMR probes. In spite of their excellent properties, DNA containing 2FA has not been studied well. For fundamental understanding and future applications to the development of functional nucleic acids, we characterized 2FA‐containing oligonucleotides for canonical right‐handed DNA duplex, G‐quadruplex, and i‐motif structures. Properties of 2FA were similar to native adenine due to the small size of the fluorine atom, but it showed unique features caused by high electronegativity. This work provides useful information for future application of 2FA‐modified DNA.

  DOI：

  10.1002/cbic.202200222
• 作为产物：
  描述：

  三甲基氯硅烷 、 2-氟-6-氨基嘌呤 在 六甲基二硅氮烷 作用下， 反应 20.5h， 生成 2-fluoro-9-trimethylsilyladenine
  参考文献：
  名称：

  基于核苷的抗原生动物化合物的合成和活性。

  摘要：

  寄生虫的原生动物利用挽救途径合成嘌呤并产生必需的活性核苷酸，而哺乳动物则能够从头进行生物合成。这种差异为设计潜在的新抗原生动物化合物提供了机会。基于以下假设制备了一系列47个腺苷类似物，它们在2、6和5'位置有修饰，这是基于这样的假设，即此类化合物可作为原生动物核苷挽救酶的底物，而在哺乳动物细胞中仍然是难降解的。核苷经设计可在被寄生虫裂解为相应的嘌呤碱基后产生有毒代谢物。制备了具有相似目的的三种7-脱氮鸟苷衍生物。所有这些化合物均经过体外抗T. brucei（非洲昏睡病），T。cruzi（恰加斯氏病），L。donovani（利什曼病）和恶性疟原虫（疟疾）。为了确定抗原生动物核苷的治疗选择性指数（SI），还测定了它们对大鼠成肌细胞系的细胞毒性。一种腺苷衍生物被证明对恶性疟原虫高度有效（IC50 = 110nM，SI = 1010），而改良的鸟苷则对杜氏疟原虫（IC50 = 60nM，SI =

  DOI：

  10.1016/j.bmc.2017.02.016

文献信息

• [EN] NUCLEOSIDE-BASED ANTI-BACTERIAL AND ANTI-PROTOZOAN DRUGS<br/>[FR] MÉDICAMENTS ANTIBACTÉRIENS ET ANTI-PROTOZOAIRES À BASE DE NUCLÉOSIDES
  申请人：UTI LIMITED PARTNERSHIP

  公开号：WO2016168911A1

  公开（公告）日：2016-10-27

  The present invention is directed to purine nucleoside analogs of the general formula (I) or salts and pharmaceutical compositions comprising such compounds and salts, which are useful as anti-protozoan agents. The invention is also directed to methods for treating a protozoan infection in a mammal and use of the compounds for inhibiting the growth of protozoa.

  本发明涉及通式（I）的嘌呤核苷类似物或其盐以及包含这些化合物和盐的药物组合物，这些化合物和盐可用作抗原生虫剂。该发明还涉及用于治疗哺乳动物原生动物感染的方法以及利用这些化合物抑制原生动物生长的用途。
• 2-fluoro-9-trimethylsilyladenine
  申请人：Ash Stevens, Inc.

  公开号：US05917040A1

  公开（公告）日：1999-06-29

  A process for the preparation of 2-fluoro-9- (2,3,5-tri-O-benzyl-beta-D-arabinofuranosyl)adenine (I) is described. The process involves reacting a protected 2-fluoro adenine with a protected chlorosugar under controlled conditions of temperature (80-85.degree. C.) to produce (I), rather than using a process involving fluorinating a 2-substituted nucleoside precursor of (I).

  本发明描述了一种制备2-氟-9-(2,3,5-三-O-苯甲基-β-D-阿拉伯呋喃糖基)腺嘌呤(I)的过程。该过程涉及在温度(80-85℃)控制条件下将保护的2-氟腺嘌呤与保护的氯代糖反应，以产生(I)，而不是使用涉及氟化(I)的2-取代核苷前体的过程。
• Synthesis of 2‘,5‘-Dideoxy-2-fluoroadenosine and 2‘,5‘-Dideoxy-2,5‘-difluoroadenosine:  Potent P-Site Inhibitors of Adenylyl Cyclase
  作者：Song Ye、Martha M. Rezende、Wei-Ping Deng、Brian Herbert、John W. Daly、Roger A. Johnson、Kenneth L. Kirk

  DOI：10.1021/jm0303599

  日期：2004.2.1

  Glycosylation of 2-fluoroadenine with the appropriate protected thioglycoside derivatives, followed by deprotection and anomer separation, produced the alpha- and beta-anomers of 2',5'-dideoxy-2-fluoroadenosine (1), 2',5'-dideoxy-2,5'-difluoroadenosine (2), and 2'-deoxy-2-fluoroadenosine (3). These were examined as P-site inhibitors of adenylyl cyclase. The presence of fluorine on the purine ring increased potency of inhibition, and the most potent compound, beta-2',5'-dideoxy-2-fluoroadenosine (1b), was 3 times more potent than beta-2',5'-dideoxyadenosine.
• Synthesis and activity of nucleoside-based antiprotozoan compounds
  作者：Huu-Anh Tran、Zhaoyan Zheng、Xianghui Wen、Srinivasan Manivannan、Arnaud Pastor、Marcel Kaiser、Reto Brun、Floyd F. Snyder、Thomas G. Back

  DOI：10.1016/j.bmc.2017.02.016

  日期：2017.4

  (IC50=110nM and SI=1010, while a modified guanosine displayed potent activities against L. donovani (IC50=60nM, SI=2720) and T. brucei (IC50=130nM, SI=1250), as well as moderate activity against T. cruzi (IC50=3.4µM, SI=48). These results provide proof of concept for the nucleoside-based antiprotozoan strategy, as well as potential lead compounds for further optimization and validation.

  寄生虫的原生动物利用挽救途径合成嘌呤并产生必需的活性核苷酸，而哺乳动物则能够从头进行生物合成。这种差异为设计潜在的新抗原生动物化合物提供了机会。基于以下假设制备了一系列47个腺苷类似物，它们在2、6和5'位置有修饰，这是基于这样的假设，即此类化合物可作为原生动物核苷挽救酶的底物，而在哺乳动物细胞中仍然是难降解的。核苷经设计可在被寄生虫裂解为相应的嘌呤碱基后产生有毒代谢物。制备了具有相似目的的三种7-脱氮鸟苷衍生物。所有这些化合物均经过体外抗T. brucei（非洲昏睡病），T。cruzi（恰加斯氏病），L。donovani（利什曼病）和恶性疟原虫（疟疾）。为了确定抗原生动物核苷的治疗选择性指数（SI），还测定了它们对大鼠成肌细胞系的细胞毒性。一种腺苷衍生物被证明对恶性疟原虫高度有效（IC50 = 110nM，SI = 1010），而改良的鸟苷则对杜氏疟原虫（IC50 = 60nM，SI =
• Characterization of 2‐Fluoro‐2’‐deoxyadenosine in Duplex, G‐Quadruplex and i‐Motif
  作者：Shingo Hirashima、Hiroshi Sugiyama、Soyoung Park

  DOI：10.1002/cbic.202200222

  日期：2022.6.20

  AbstractAmong various kinds of fluorine‐substituted biomolecules, 2‐fluoroadenine (2FA) and its derivatives have been actively investigated as therapeutic reagents, radio‐sensitizers, and 19F NMR probes. In spite of their excellent properties, DNA containing 2FA has not been studied well. For fundamental understanding and future applications to the development of functional nucleic acids, we characterized 2FA‐containing oligonucleotides for canonical right‐handed DNA duplex, G‐quadruplex, and i‐motif structures. Properties of 2FA were similar to native adenine due to the small size of the fluorine atom, but it showed unique features caused by high electronegativity. This work provides useful information for future application of 2FA‐modified DNA.