2,5,6-三氯-1H-吲哚 | 286949-65-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 中文名称: 2,5,6-三氯-1H-吲哚
• 英文名称: 2,5,6-trichloroindole
• 英文别名: 2,5,6-trichloro-1H-indole
• CAS: 286949-65-3
• 化学式: C₈H₄Cl₃N
• 分子量: 220.485
• InChiKey: BNBOKCJLKBLBQD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  15.8
• 氢给体数：
  1
• 氢受体数：
  0

反应信息

• 作为反应物：
  描述：

  2,5,6-三氯-1H-吲哚 在 四丁基氟化铵 、 sodium hydride 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 17.17h， 生成 1-(2,3-O-isopropylidene-β-D-ribofuranosyl)-2,5,6-trichloroindole
  参考文献：
  名称：

  Synthesis and Antiviral Evaluation of Trisubstituted Indole N-Nucleosides as Analogues of 2,5,6-Trichloro-1-(β-d-ribofuranosyl)benzimidazole (TCRB)

  摘要：

  2,5,6-Trichloro-1-(beta-D-ribofuranosyl)benzimidazole (TCRB) and 2-bromo-5,6-dichloro-1-(beta-D-ribofuranosyl)benzimidazole (BDCRB) are nucleosides that exhibit strong and selective activity against human cytomegalovirus (HCMV). Selected polyhalogenated indole nucleosides have now been synthesized as 3-deaza analogues of the benzimidazole nucleosides using the sodium salt glycosylation method. 2-Benzylthio-1-[2-deoxy-3,5-bis-O-(4-methylbenzoyl)-beta-D-erythropentofuranosyl]-5,6-dichloroindole (8) was prepared stereoselectively via the coupling of a 2-deoxyribofuranosyl alpha-chloride derivative with the sodium salt of 2-benzylthio-5,6-dichloroindole (5). Compound 8 was then elaborated into the targeted 2-benzylthio-1-(beta-D-ribofuranosyl)-5,6-dichloroindole (18) in five steps. 2,5,6-Trichloro-(1-beta-D-ribofuranosyl)indole (19) was prepared using the same synthetic route with 2,5,6-trichloroindole (6) as the starting material. We were subsequently able to prepare 19 in three steps using a modification of the sodium salt glycosylation method. 2-Bromo-5,6-dichloro-1-(beta-D-ribofuranosyl)indole (25) was also prepared using the same procedures. Target compounds were tested for activity against HCMV, herpes simplex virus type 1 (HSV-1), and human herpes virus six (HHV-6) and for cytotoxicity. All of the compounds were less active against HCMV than TCRB and weakly active or inactive against HSV-1 and HHV-6.

  DOI：

  10.1021/jm990320x
• 作为产物：
  描述：

  2-（4,5-二氯-2-硝基苯基）乙酸甲酯 在 platinum(IV) oxide 咪唑 、 氢气 、 溶剂黄146 、 三氯氧磷 作用下， 以 1,2-二氯乙烷 为溶剂， 20.0 ℃ 、275.8 kPa 条件下， 反应 22.5h， 生成 2,5,6-三氯-1H-吲哚
  参考文献：
  名称：

  Synthesis and Antiviral Evaluation of Trisubstituted Indole N-Nucleosides as Analogues of 2,5,6-Trichloro-1-(β-d-ribofuranosyl)benzimidazole (TCRB)

  摘要：

  2,5,6-Trichloro-1-(beta-D-ribofuranosyl)benzimidazole (TCRB) and 2-bromo-5,6-dichloro-1-(beta-D-ribofuranosyl)benzimidazole (BDCRB) are nucleosides that exhibit strong and selective activity against human cytomegalovirus (HCMV). Selected polyhalogenated indole nucleosides have now been synthesized as 3-deaza analogues of the benzimidazole nucleosides using the sodium salt glycosylation method. 2-Benzylthio-1-[2-deoxy-3,5-bis-O-(4-methylbenzoyl)-beta-D-erythropentofuranosyl]-5,6-dichloroindole (8) was prepared stereoselectively via the coupling of a 2-deoxyribofuranosyl alpha-chloride derivative with the sodium salt of 2-benzylthio-5,6-dichloroindole (5). Compound 8 was then elaborated into the targeted 2-benzylthio-1-(beta-D-ribofuranosyl)-5,6-dichloroindole (18) in five steps. 2,5,6-Trichloro-(1-beta-D-ribofuranosyl)indole (19) was prepared using the same synthetic route with 2,5,6-trichloroindole (6) as the starting material. We were subsequently able to prepare 19 in three steps using a modification of the sodium salt glycosylation method. 2-Bromo-5,6-dichloro-1-(beta-D-ribofuranosyl)indole (25) was also prepared using the same procedures. Target compounds were tested for activity against HCMV, herpes simplex virus type 1 (HSV-1), and human herpes virus six (HHV-6) and for cytotoxicity. All of the compounds were less active against HCMV than TCRB and weakly active or inactive against HSV-1 and HHV-6.

  DOI：

  10.1021/jm990320x

文献信息

• [EN] INDOLE ANTIVIRAL COMPOSITIONS AND METHODS<br/>[FR] COMPOSITIONS ANTIVIRALES A BASE D'INDOLE ET PROCEDES CORRESPONDANTS
  申请人：UNIV MICHIGAN

  公开号：WO2005034943A1

  公开（公告）日：2005-04-21

  The present invention provides novel chemical compounds and methods for their use. In particular, the present invention provides indole derivatives (e.g. as shown in Formula (I)) and related compounds and methods of using indole derivatives and related compounds as therapeutic agents to treat a number of conditions, including those associated with viral infection and cardiovascular diseases.

  本发明提供了新颖的化合物和它们的使用方法。具体来说，本发明提供了吲哚衍生物（例如如公式（I）所示）和相关化合物，以及使用吲哚衍生物和相关化合物作为治疗剂治疗多种疾病的方法，包括与病毒感染和心血管疾病相关的疾病。
• 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
• Design, Synthesis, and Antiviral Evaluation of Some Polyhalogenated Indole <i>C</i>-nucleosides
  作者：Jiong J. Chen、Yuan Wei、John D. Williams、John C. Drach、Leroy B. Townsend

  DOI：10.1080/15257770500265646

  日期：2005.9.1

  A mild Knoevenagel coupling reaction between an indol-2-thione and a ribofuranose derivative was developed for the synthesis of 2-benzylthio-5,6-dichloro-3-(β-D-ribofuranosyl)indole (12). 3-(β-D-ribofuranosyl)-2,5,6-trichloroindole (16) was prepared from 12 in 4 steps. A Lewis acid-mediated glycosylation method was then developed to prepare the targeted 2-haloindole C-nucleoside 16 stereoselectively

  2,5,6-Trichloro-1-(β-D-ribofuranosyl)benzimidazole (TCRB), 2-bromo-5,6-dichloro-1-(β-D-ribofuranosyl)benzimidazole (BDCRB) 和 2-benzylthio- 5,6-二氯-1-(β-D-呋喃核糖基)苯并咪唑 (BTDCRB) 是苯并咪唑核苷，具有强大的选择性抗 HCMV 活性。多卤化吲哚 C-核苷制备为苯并咪唑核苷 TCRB 和 BDCRB 的 1-脱氮类似物。开发了 indol-2-thione 和 ribofuranose 衍生物之间的温和 Knoevenagel 偶联反应，用于合成 2-benzylthio-5,6-dichloro-3-(β-D-ribofuranosyl) indole (12)。3-(β-D-呋喃核糖基)-2,5,6-三氯吲哚 (16) 由 12
• Synthesis, Antiviral Activity, and Mode of Action of Some 3-Substituted 2,5,6-Trichloroindole 2‘- and 5‘-Deoxyribonucleosides
  作者：John D. Williams、Roger G. Ptak、John C. Drach、Leroy B. Townsend

  DOI：10.1021/jm0400606

  日期：2004.11.1

  time-of-addition studies using FTCRI and by the resistance of TCRB-resistant strains of HCMV to four different 3-substituted indole ribonucleosides. The 2'-deoxy analogues of the trichlorinated indole nucleosides also had potent antiviral activity, in contrast to decreased activity and selectivity observed for 2'-deoxy TCRB compared to TCRB. In addition, 3-acetyl-2,5,6-trichloro-1-(2-deoxy-beta-d-ribofuranosyl)indole

  已合成了一系列氯化吲哚核苷，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。报道的3-甲酰基-2,5,6-三氯-1-（β-D-呋喃呋喃糖基）吲哚（FTCRI）和3-氰基-2,5,6-三氯的2'-和5'-脱氧衍生物通过对适当的3-未取代的糖修饰的核苷类似物进行修饰或通过将3-取代的杂环与受保护的α-氯糖进行糖基化来合成-1-（β-D-呋喃呋喃糖基）吲哚（CTCRI）。修饰的部分原因是与相应的一系列氯化苯并咪唑核糖核苷的结构相似，以及2,5,6-三氯-1-（β-D-呋喃呋喃糖基）苯并咪唑（TCRB）的5'-脱氧类似物非常重要对HCMV有效。5' FTCRI和CTCRI的-脱氧类似物的活性几乎与FTCRI和CTCRI一样，这表明氯化苯并咪唑核苷和氯化吲哚核苷的作用方式相似。使用FTCRI的加法时间研究以及HCMV的TCRB抗性菌株对四种不同的3个取代的吲哚
• Indole antiviral compositions and methods
  申请人：Townsend B. Leroy

  公开号：US20050143329A1

  公开（公告）日：2005-06-30

  The present invention provides novel chemical compounds, and methods for their use. In particular, the present invention provides indole derivatives (e.g. as shown in Formula (I)) and related compounds and methods of using indole derivatives and related compounds as therapeutic agents to treat a number of conditions, including those associated with viral infection and cardiovascular diseases.

  本发明提供了新的化合物和其使用方法。特别地，本发明提供吲哚衍生物（例如如式（I）所示）和相关化合物以及使用吲哚衍生物和相关化合物作为治疗剂治疗多种疾病的方法，包括与病毒感染和心血管疾病有关的疾病。