4-(4-氯苯胺基)-4-氧代丁酸 | 2104-66-7

• 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: 4-(4-氯苯胺基)-4-氧代丁酸
• 英文名称: 8-(methylthio)guanosine
• 英文别名: 2-Amino-9-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-8-(methylthio)-1H-purin-6(9H)-one；2-amino-9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-8-methylsulfanyl-1H-purin-6-one
• CAS: 2104-66-7
• 化学式: C₁₁H₁₅N₅O₅S
• 分子量: 329.337
• InChiKey: VEABMYFEYLXTSD-UUOKFMHZSA-N

物化性质

• 密度：
  2.12±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  181
• 氢给体数：
  5
• 氢受体数：
  8

制备方法与用途

8-（甲硫基）鸟苷是一种鸟苷类似物，具有一定的免疫刺激活性，在某些动物模型中还能诱导I型干扰素产生，从而发挥抗病毒作用。研究显示，鸟苷类似物的功能活性依赖于Toll样受体7（TLR7）的激活。

反应信息

• 作为反应物：
  描述：

  4-(4-氯苯胺基)-4-氧代丁酸 在 盐酸 、 双氧水 、 重水 、 溶剂黄146 、 lithium hydroxide 作用下， 反应 72.0h， 生成 鸟苷
  参考文献：
  名称：

  Oxidation of 8-thioguanosine gives redox-responsive hydrogels and reveals intermediates in a desulfurization pathway

  摘要：

  8-硫代鸟嘌呤的氧化产生二硫化物，形成氧化还原响应性水凝胶，并且在8-硫代鸟嘌呤的氧化脱硫过程中是一个中间体。

  DOI：

  10.1039/d0cc02926b
• 作为产物：
  描述：

  8-溴鸟苷 在 potassium carbonate 、 硫脲 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.0h， 生成 4-(4-氯苯胺基)-4-氧代丁酸
  参考文献：
  名称：

  8-Substituted guanosine and 2'-deoxyguanosine derivatives as potential inducers of the differentiation of Friend erythroleukemia cells

  摘要：

  A variety of 8-substituted guanosine and 2'-deoxyguanosine derivatives were synthesized and tested as inducers of the differentiation of Friend murine erythroleukemia cells in culture. The most active agents in the guanosine series were 8-substituted-N(CH3)2, -NHCH3, -NH2, -OH, and -SO2CH3, which caused 68, 42, 34, 33, and 30% of erythroleukemia cells to attain benzidine positivity, a functional measure of maturation, at concentrations of 5, 1, 0.4, 5, and 5 mM, respectively. The 8-OH derivative of the 2'-deoxyguanosine series produced comparable activity, causing 62% benzidine-positive cells at a level of 0.2 mM. These findings indicate that 8-substituted analogues of guanosine and 2'-deoxyguanosine have the potential to terminate leukemia cell proliferation through conversion to end-stage differentiated cells.

  DOI：

  10.1021/jm00147a012

文献信息

• Chikungunya virus inhibition by synthetic coumarin–guanosine conjugates
  作者：Jih Ru Hwu、Wen-Chieh Huang、Shu-Yu Lin、Kui-Thong Tan、Yu-Chen Hu、Fa-Kuen Shieh、Sergey O. Bachurin、Alexey Ustyugov、Shwu-Chen Tsay

  DOI：10.1016/j.ejmech.2019.01.037

  日期：2019.3

  lack of effective vaccines and antiviral drugs to intervene this disease, 21 new conjugated compounds were designed and synthesized by coupling of 6,8-dithioguanosine at its C-6 position with 3-(chloromethyl)coumarins bearing an F, Cl, Br, Me, or –OMe substituent through the –SCH2– joint. Meanwhile, an organic “dummy” ligand (e.g., methyl, benzyl, and naphthylmethyl) or a coumarinyl moiety was attached

  自1952年在非洲坦any尼喀（Tanganyika）发现以来，基孔肯雅病毒（CHIKV）暴发已在非洲，亚洲，欧洲和美洲发生。直到现在，基孔肯雅热已在近40个国家蔓延。由于缺乏有效的疫苗和抗病毒药物来干预该疾病，因此设计并合成了21种新的共轭化合物，方法是将C-6位的6,8-二硫代鸟苷与带有F，Cl，Br的3-（氯甲基）香豆素偶联，Me或–OMe取代基通过–SCH 2 –接头。同时，有机“虚拟”配体（例如，甲基，苄基和萘甲基）或香豆素基部分连接在C-8位置。通过高通量筛选，发现这些新结合物中的三种可有效抑制Vero细胞中的CHIKV（EC 50 = 9.9–13.9μM），并且显示出低毒性（CC 50  = 96.5–212μM）。选择性指数值为9.37–21.7。推导了它们的结构-活性关系，这表明香豆素部分是必不可少的，并且-OMe基团的存在增强了抗病毒活性。
• Supramolecular Helices via Self-Assembly of 8-Oxoguanosines
  作者：Tatiana Giorgi、Stefano Lena、Paolo Mariani、Mauro A. Cremonini、Stefano Masiero、Silvia Pieraccini、Jürgen P. Rabe、Paolo Samorì、Gian Piero Spada、Giovanni Gottarelli

  DOI：10.1021/ja0364827

  日期：2003.12.1

  The cooperative effect of solvophobic interactions and hydrogen bonding has been exploited to self-assemble supramolecular helical architectures of 8-oxoguanosines in different environments. This self-assembly into helical structures is completely different from that of the parent guanosines which, in the same experimental conditions, form flat, ribbonlike structures. While optical microscopy and X-ray diffraction suggest a chiral columnar aggregate in the LC phase, NMR and Circular Dichroism reveal the presence of a helical structures in solution. Scanning Tunneling Microscopy made it possible to visualize hexagonally arranged G-quartets on graphite, which are sections of the helices packed with their long axis perpendicular to the basal plane of the substrate. Due to their rectifying electrical properties, such helices are interesting for fabricating (opto)electronic biodevices.
• US4643992A
  申请人：——

  公开号：US4643992A

  公开（公告）日：1987-02-17
• US4746651A
  申请人：——

  公开号：US4746651A

  公开（公告）日：1988-05-24
• US4948730A
  申请人：——

  公开号：US4948730A

  公开（公告）日：1990-08-14