5-氯-3-(2,6-二氯苯基)磺酰基-1H-吲哚-2-甲酰胺 | 540740-93-0

• 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: 5-氯-3-(2,6-二氯苯基)磺酰基-1H-吲哚-2-甲酰胺
• 英文名称: 5-chloro-3-((2,6-dichlorophenyl)sulfonyl)-1H-indole-2-carboxamide
• 英文别名: 1H-Indole-2-carboxamide, 5-chloro-3-[(2,6-dichlorophenyl)sulfonyl]-；5-chloro-3-(2,6-dichlorophenyl)sulfonyl-1H-indole-2-carboxamide
• CAS: 540740-93-0
• 化学式: C₁₅H₉Cl₃N₂O₃S
• 分子量: 403.673
• InChiKey: JMMANZNYVQEICS-UHFFFAOYSA-N

物化性质

• 熔点：
  288-290 °C
• 沸点：
  681.8±55.0 °C(Predicted)
• 密度：
  1.649±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2,6-二氯苯硫酚 在 ammonium hydroxide 、 氯化亚砜 、 1,3-二溴-5,5-二甲基海因 、 sodium hydride 、 间氯过氧苯甲酸 作用下， 以 乙醇 、 氯仿 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 2.25h， 生成 5-氯-3-(2,6-二氯苯基)磺酰基-1H-吲哚-2-甲酰胺
  参考文献：
  名称：

  Indolylarylsulfones Carrying a Heterocyclic Tail as Very Potent and Broad Spectrum HIV-1 Non-nucleoside Reverse Transcriptase Inhibitors

  摘要：

  We synthesized new indolylarylsulfone (IAS) derivatives carrying a heterocyclic tail at the indole-2-carboxamide nitrogen as potential anti-HIV/AIDS agents. Several new IASs yielded EC50 values <1.0 nM against HIV-1 WT and mutant strains in MT-4 cells. The (R)-11 enantiomer proved to be exceptionally potent against the whole viral panel; in the reverse transcriptase (RT) screening assay, it was remarkably superior to NVP and EFV and comparable to ETV. The binding poses were consistent with the one previously described for the IAS non-nucleoside reverse transcriptase inhibitors. Docking studies showed that the methyl group of (R)-11 points toward the cleft created by the K103N mutation, different from the corresponding group of (S)-11. By calculating the solvent-accessible surface, we observed that the exposed area of RT in complex with (S)-11 was larger than the area of the (R)-11 complex. Compounds 6 and 16 and enantiomer (R)-11 represent novel robust lead compounds of the IAS class.

  DOI：

  10.1021/jm5011622

文献信息

• Novel Indolyl Aryl Sulfones Active against HIV-1 Carrying NNRTI Resistance Mutations:  Synthesis and SAR Studies
  作者：Romano Silvestri、Gabriella De Martino、Giuseppe La Regina、Marino Artico、Silvio Massa、Laura Vargiu、Massimo Mura、Anna Giulia Loi、Tiziana Marceddu、Paolo La Colla

  DOI：10.1021/jm0211063

  日期：2003.6.1

  The potent anti-HIV-1 activities of L-737,126 (2) and PAS sulfones prompted us to design and test against HIV-1 in acutely infected MT-4 cells a number of novel 1- and 3-benzenesulfonylindoles. Indoles belonging to the 1-benzenesulfonyl series were found poorly or totally inactive. On the contrary, some of the 3-benzenesulfonyl derivatives turned out to be as potent as 2, being endowed with potencies in the low nanomolar concentration range. In particular, (2-methylphenyl)sulfonyl (72) and (3-methylphenyl)sulfonyl (73) derivatives showed EC50 values of 1 nM. Introduction of two methyl groups at positions 3 and 5 of the phenyl ring of 2 furnished derivatives (80 and 83) which showed very potent and selective anti-HIV-1 activity not only against the wt strain, but also against mutants carrying NNRTI-resistant mutations at positions 103 and 181 of the reverse transcriptase gene.
• Indolylarylsulfones Carrying a Heterocyclic Tail as Very Potent and Broad Spectrum HIV-1 Non-nucleoside Reverse Transcriptase Inhibitors
  作者：Valeria Famiglini、Giuseppe La Regina、Antonio Coluccia、Sveva Pelliccia、Andrea Brancale、Giovanni Maga、Emmanuele Crespan、Roger Badia、Eva Riveira-Muñoz、José A. Esté、Rosella Ferretti、Roberto Cirilli、Claudio Zamperini、Maurizio Botta、Dominique Schols、Vittorio Limongelli、Bruno Agostino、Ettore Novellino、Romano Silvestri

  DOI：10.1021/jm5011622

  日期：2014.12.11

  We synthesized new indolylarylsulfone (IAS) derivatives carrying a heterocyclic tail at the indole-2-carboxamide nitrogen as potential anti-HIV/AIDS agents. Several new IASs yielded EC50 values <1.0 nM against HIV-1 WT and mutant strains in MT-4 cells. The (R)-11 enantiomer proved to be exceptionally potent against the whole viral panel; in the reverse transcriptase (RT) screening assay, it was remarkably superior to NVP and EFV and comparable to ETV. The binding poses were consistent with the one previously described for the IAS non-nucleoside reverse transcriptase inhibitors. Docking studies showed that the methyl group of (R)-11 points toward the cleft created by the K103N mutation, different from the corresponding group of (S)-11. By calculating the solvent-accessible surface, we observed that the exposed area of RT in complex with (S)-11 was larger than the area of the (R)-11 complex. Compounds 6 and 16 and enantiomer (R)-11 represent novel robust lead compounds of the IAS class.