3-[(3,5-dimethylphenyl)sulfonyl]-5-nitro-1H-indole-2-carboxylic acid | 1140948-51-1

• 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
• 英文名称: 3-[(3,5-dimethylphenyl)sulfonyl]-5-nitro-1H-indole-2-carboxylic acid
• CAS: 1140948-51-1
• 化学式: C₁₇H₁₄N₂O₆S
• 分子量: 374.374
• InChiKey: FRGFRSCSMKVFPS-UHFFFAOYSA-N

物化性质

• 熔点：
  266-275 °C(Solvent: Ethanol)
• 沸点：
  705.2±60.0 °C(predicted)
• 密度：
  1.514±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.22
• 重原子数：
  26.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  130.37
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  3-[(3,5-dimethylphenyl)sulfonyl]-5-nitro-1H-indole-2-carboxylic acid 、 DL-丙氨酸乙酯盐酸盐 在 卡特缩合剂 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以99%的产率得到ethyl 2-[3-[(3,5-dimethylphenyl)sulfonyl]-5-nitro-1H-indole-2-carboxamido]propanoate
  参考文献：
  名称：

  Indolylarylsulfones Bearing Natural and Unnatural Amino Acids. Discovery of Potent Inhibitors of HIV-1 Non-Nucleoside Wild Type and Resistant Mutant Strains Reverse Transcriptase and Coxsackie B4 Virus

  摘要：

  New potent indolylarylsulfone (IAS) HIV-I NNRTIs were obtained by coupling natural and unnatural amino acids to the 2-carboxamide and introducing different electron-withdrawing substituents at position 4 and 5 of the indole nucleus. The new IASs inhibited the HIV-1 replication in human T-lymphocyte (CEM) cells at low/subnanomolar concentration and were weakly cytostatic. Against the mutant L100I, K103N, and Y181C RT HIV-1 strains in CEM cells, sulfones 3, 4, 19, 27, and 31 were comparable to EFV. The new IASs were inhibitors to Coxsackie B4 virus at low micromolar (2-9 mu M) concentrations. Superimposition of PLANTS docked conformations of IASs 19 and 9 revealed different hydrophobic interactions of the 3,5-dimethylphenyl group, for which a staking interaction with Tyr181 aromatic side chain was observed. The binding mode of 19 was not affected by the L100I mutation and was consistent with the interactions reported for the WT strain.

  DOI：

  10.1021/jm801470b
• 作为产物：
  描述：

  ethyl 3-[(3,5-dimethylphenyl)sulfonyl]-5-nitro-1H-indole-2-carboxylate 在 lithium hydroxide monohydrate 、 水 作用下， 以 四氢呋喃 为溶剂， 反应 77.0h， 以83%的产率得到3-[(3,5-dimethylphenyl)sulfonyl]-5-nitro-1H-indole-2-carboxylic acid
  参考文献：
  名称：

  Indolylarylsulfones Bearing Natural and Unnatural Amino Acids. Discovery of Potent Inhibitors of HIV-1 Non-Nucleoside Wild Type and Resistant Mutant Strains Reverse Transcriptase and Coxsackie B4 Virus

  摘要：

  New potent indolylarylsulfone (IAS) HIV-I NNRTIs were obtained by coupling natural and unnatural amino acids to the 2-carboxamide and introducing different electron-withdrawing substituents at position 4 and 5 of the indole nucleus. The new IASs inhibited the HIV-1 replication in human T-lymphocyte (CEM) cells at low/subnanomolar concentration and were weakly cytostatic. Against the mutant L100I, K103N, and Y181C RT HIV-1 strains in CEM cells, sulfones 3, 4, 19, 27, and 31 were comparable to EFV. The new IASs were inhibitors to Coxsackie B4 virus at low micromolar (2-9 mu M) concentrations. Superimposition of PLANTS docked conformations of IASs 19 and 9 revealed different hydrophobic interactions of the 3,5-dimethylphenyl group, for which a staking interaction with Tyr181 aromatic side chain was observed. The binding mode of 19 was not affected by the L100I mutation and was consistent with the interactions reported for the WT strain.

  DOI：

  10.1021/jm801470b

文献信息

• 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.