methyl 3-[5-chloro-3-[(3,5-dimethylphenyl)sulfonyl]-4-fluoro-1H-indole-2-carboxamido]propanoate | 1140948-80-6

• 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: methyl 3-[5-chloro-3-[(3,5-dimethylphenyl)sulfonyl]-4-fluoro-1H-indole-2-carboxamido]propanoate
• CAS: 1140948-80-6
• 化学式: C₂₁H₂₀ClFN₂O₅S
• 分子量: 466.918
• InChiKey: OJAZZDBMXFYUCK-UHFFFAOYSA-N

物化性质

• 熔点：
  205-268 °C(Solvent: Ethanol)
• 沸点：
  726.2±60.0 °C(predicted)
• 密度：
  1.405±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  31.0
• 可旋转键数：
  6.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  105.33
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  methyl 3-[5-chloro-3-[(3,5-dimethylphenyl)sulfonyl]-4-fluoro-1H-indole-2-carboxamido]propanoate 在 ammonium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 3.0h， 以94%的产率得到N-(3-amino-3-oxopropyl)-5-chloro-3-[(3,5-dimethylphenyl)-sulfonyl]-4-fluoro-1H-indole-2-carboxamide
  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：

  5-chloro-3-[(3,5-dimethylphenyl)sulfonyl]-4-fluoro-1H-indole-2-carboxylic acid 、 3-氨基丙酸甲酯盐酸盐 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73%的产率得到methyl 3-[5-chloro-3-[(3,5-dimethylphenyl)sulfonyl]-4-fluoro-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