3-cyano-2,5,6-trichloro-1-(2,3-O-isopropylidene-β-D-ribofuranosyl)indole | 801300-06-1

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 吲哚核糖核苷和核糖核苷酸
• 英文名称: 3-cyano-2,5,6-trichloro-1-(2,3-O-isopropylidene-β-D-ribofuranosyl)indole
• 英文别名: 1-[(3aR,4R,6R,6aR)-6-(hydroxymethyl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-2,5,6-trichloroindole-3-carbonitrile
• CAS: 801300-06-1
• 化学式: C₁₇H₁₅Cl₃N₂O₄
• 分子量: 417.676
• InChiKey: HGJCLMLMADUHMT-IXYNUQLISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  26
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  76.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-cyano-2,5,6-trichloro-1-(2,3-O-isopropylidene-β-D-ribofuranosyl)indole 在 三氟乙酸 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.03h， 生成 3-cyano-2-pyrrolidino-5,6-dichloro-1-(β-D-ribofuranosyl)indole
  参考文献：
  名称：

  Synthesis and Antiviral Activity of Some 2-Substituted 3-Formyl-and 3-Cyano-5,6-Dichloroindole Nucleosides

  摘要：

  A series of dichlorinated indole nucleosides has been synthesized and tested for activity against human cytomegalovirus (HCMV) and herpes simplex virus type-1 (HSV-1) and for cytotoxicity. The isopropylidene-protected analogs of the previously reported 3-formyl-2,5,6-trichloro-1-(beta-D-ribofuranosyl)indole (FTCRI) and 3-cyano-2,5,6-trichloro-1-(beta-D-ribofuranosyl)indole (CTCRI) were modified by nucleophilic displacement of the 2-chloro substituent using secondary amines. Deprotection of the intermediates provided 2-substituted analogs of FTCRI and CTCRI in good yield. There was a significant difference in reactivity between the isopropylidene-protected and the fully deprotected FTCRI and CTCRI with respect to nucleophilic displacement of the 2-chloro substituent using dialkylamines. This difference in reactivity was not observed with monoalkylamines or with alkoxides, and the corresponding 2-alkylamino- and 2-methoxy substituted analogs were synthesized from FTCRI and CTCRI directly. None of the synthesized analogs demonstrated potent antiviral activity without some corresponding cytotoxicity.

  DOI：

  10.1080/15257770500265836
• 作为产物：
  描述：

  2,3-O-isopropylidene-5-O-dimethyl-t-butylsiloxy-β-D-ribofuranose 在 四氯化碳 、 六甲基磷酰三胺 、 sodium hydride 、 cesium fluoride 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 36.67h， 生成 3-cyano-2,5,6-trichloro-1-(2,3-O-isopropylidene-β-D-ribofuranosyl)indole
  参考文献：
  名称：

  某些3取代的2,5,6-三氯吲哚核苷的设计，合成和抗病毒活性。

  摘要：

  已经合成了一系列三氯化吲哚核苷，并测试了其对人巨细胞病毒（HCMV）和1型单纯疱疹病毒（HSV-1）的活性以及细胞毒性。设计了先前报道的在杂环的3位上的2,5,6-三氯-1-（β-d-核呋喃呋喃糖基）吲哚的修饰部分是为了测试我们的假设，即在该位置需要氢键键合才能具有抗病毒活性。使用3-位的亲电加成或通过合成修饰的吲哚杂环，然后进行糖基化和糖的修饰来合成类似物。在3位的修饰中，只有那些具有氢键接受特性的类似物才具有抗HCMV的活性（例如3-甲酰基-2,5,6-三氯-1-（β-D-呋喃呋喃糖基）吲哚，FTCRI ，IC50 = 0.23 microM）。反过来，在3位上具有非氢键取代基的类似物（例如3-甲基-2,5,6-三氯-1-（β-D-核呋喃糖基）吲哚）的活性（IC50 = 32 microM）比具有必要的氢键能力的那些。获得了FTCRI的5'-O-酰基类似物作为中间体，并且发现它也是HCMV的有效抑制剂（IC50

  DOI：

  10.1021/jm0400146

文献信息

• Design, Synthesis, and Antiviral Activity of Certain 3-Substituted 2,5,6-Trichloroindole Nucleosides
  作者：John D. Williams、Jiong J. Chen、John C. Drach、Leroy B. Townsend

  DOI：10.1021/jm0400146

  日期：2004.11.1

  with the requisite hydrogen-bonding capacity. The 5'-O-acyl analogue of FTCRI was obtained as an intermediate and also found to be a potent inhibitor of HCMV (IC50 < 0.1 microM). The synthesis of some additional 5'-O-acylated analogues did not provide a compound with increased antiviral activity. None of the indole nucleosides had significant activity against HSV-1, and none were cytotoxic to uninfected

  已经合成了一系列三氯化吲哚核苷，并测试了其对人巨细胞病毒（HCMV）和1型单纯疱疹病毒（HSV-1）的活性以及细胞毒性。设计了先前报道的在杂环的3位上的2,5,6-三氯-1-（β-d-核呋喃呋喃糖基）吲哚的修饰部分是为了测试我们的假设，即在该位置需要氢键键合才能具有抗病毒活性。使用3-位的亲电加成或通过合成修饰的吲哚杂环，然后进行糖基化和糖的修饰来合成类似物。在3位的修饰中，只有那些具有氢键接受特性的类似物才具有抗HCMV的活性（例如3-甲酰基-2,5,6-三氯-1-（β-D-呋喃呋喃糖基）吲哚，FTCRI ，IC50 = 0.23 microM）。反过来，在3位上具有非氢键取代基的类似物（例如3-甲基-2,5,6-三氯-1-（β-D-核呋喃糖基）吲哚）的活性（IC50 = 32 microM）比具有必要的氢键能力的那些。获得了FTCRI的5'-O-酰基类似物作为中间体，并且发现它也是HCMV的有效抑制剂（IC50
• Synthesis and Antiviral Activity of Some 2-Substituted 3-Formyl-and 3-Cyano-5,6-Dichloroindole Nucleosides
  作者：John D. Williams、John C. Drach、Leroy B. Townsend

  DOI：10.1080/15257770500265836

  日期：2005.9.1

  A series of dichlorinated indole nucleosides has been synthesized and tested for activity against human cytomegalovirus (HCMV) and herpes simplex virus type-1 (HSV-1) and for cytotoxicity. The isopropylidene-protected analogs of the previously reported 3-formyl-2,5,6-trichloro-1-(beta-D-ribofuranosyl)indole (FTCRI) and 3-cyano-2,5,6-trichloro-1-(beta-D-ribofuranosyl)indole (CTCRI) were modified by nucleophilic displacement of the 2-chloro substituent using secondary amines. Deprotection of the intermediates provided 2-substituted analogs of FTCRI and CTCRI in good yield. There was a significant difference in reactivity between the isopropylidene-protected and the fully deprotected FTCRI and CTCRI with respect to nucleophilic displacement of the 2-chloro substituent using dialkylamines. This difference in reactivity was not observed with monoalkylamines or with alkoxides, and the corresponding 2-alkylamino- and 2-methoxy substituted analogs were synthesized from FTCRI and CTCRI directly. None of the synthesized analogs demonstrated potent antiviral activity without some corresponding cytotoxicity.