5-溴-3-(3,5-二甲基苯基)磺酰基-1H-吲哚-2-甲酰胺 | 540740-95-2

• 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-溴-3-(3,5-二甲基苯基)磺酰基-1H-吲哚-2-甲酰胺
• 英文名称: 5-bromo-3-[(3,5dimethylphenyl)sulfonyl]-1H-indole-2-carboxamide
• 英文别名: 1H-Indole-2-carboxamide, 5-bromo-3-[(3,5-dimethylphenyl)sulfonyl]-；5-bromo-3-(3,5-dimethylphenyl)sulfonyl-1H-indole-2-carboxamide
• CAS: 540740-95-2
• 化学式: C₁₇H₁₅BrN₂O₃S
• 分子量: 407.288
• InChiKey: KDLPBLYPCKWCJH-UHFFFAOYSA-N

物化性质

• 熔点：
  >300 °C
• 沸点：
  671.8±55.0 °C(Predicted)
• 密度：
  1.580±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  哌啶 、 聚合甲醛 、 5-溴-3-(3,5-二甲基苯基)磺酰基-1H-吲哚-2-甲酰胺 以 苯 为溶剂， 反应 3.0h， 以46%的产率得到5-bromo-3-[(3,5-dimethylphenyl)sulfonyl]-N-(piperidin-1-ylmethyl)-1H-indole-2-carboxamide
  参考文献：
  名称：

  Indolylarylsulfones as HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors: New Cyclic Substituents at Indole-2-carboxamide

  摘要：

  New indolylarylsulfone derivatives bearing cyclic substituents at indole-2-carboxamide linked through a methylene/ethylene spacer were potent inhibitors of the WT HIV-1 replication in CEM and PBMC cells with inhibitory concentrations in the low nanomolar range. Against the mutant L100I and K103N RT HIV-1 strains in MT-4 cells, compounds 20, 24-26, 36, and 40 showed antiviral potency superior to that of NVP and EFV. Against these mutant strains, derivatives 20, 24-26, and 40 were equipotent to ETV. Molecular docking experiments on this novel series of IAS analogues have also suggested that the H-bond interaction between the nitrogen atom in the carboxamide chain of IAS and Glu138:B is important in the binding of these compounds. These results are in accordance with the experimental data obtained on the WT and on the mutant HIV-1 strains tested.

  DOI：

  10.1021/jm101614j
• 作为产物：
  描述：

  3,5-二甲基苯硫酚 在 ammonium hydroxide 、 三氟化硼乙醚 、 氯化铵 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 、 氯仿 为溶剂， 反应 9.0h， 生成 5-溴-3-(3,5-二甲基苯基)磺酰基-1H-吲哚-2-甲酰胺
  参考文献：
  名称：

  Novel Indolyl Aryl Sulfones Active against HIV-1 Carrying NNRTI Resistance Mutations:  Synthesis and SAR Studies

  摘要：

  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.

  DOI：

  10.1021/jm0211063

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 as HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors: New Cyclic Substituents at Indole-2-carboxamide
  作者：Giuseppe La Regina、Antonio Coluccia、Andrea Brancale、Francesco Piscitelli、Valerio Gatti、Giovanni Maga、Alberta Samuele、Christophe Pannecouque、Dominique Schols、Jan Balzarini、Ettore Novellino、Romano Silvestri

  DOI：10.1021/jm101614j

  日期：2011.3.24

  New indolylarylsulfone derivatives bearing cyclic substituents at indole-2-carboxamide linked through a methylene/ethylene spacer were potent inhibitors of the WT HIV-1 replication in CEM and PBMC cells with inhibitory concentrations in the low nanomolar range. Against the mutant L100I and K103N RT HIV-1 strains in MT-4 cells, compounds 20, 24-26, 36, and 40 showed antiviral potency superior to that of NVP and EFV. Against these mutant strains, derivatives 20, 24-26, and 40 were equipotent to ETV. Molecular docking experiments on this novel series of IAS analogues have also suggested that the H-bond interaction between the nitrogen atom in the carboxamide chain of IAS and Glu138:B is important in the binding of these compounds. These results are in accordance with the experimental data obtained on the WT and on the mutant HIV-1 strains tested.