5-chloro-3-(3,5-dimethylphenylsulfonyl)-4-fluoro-N-(morpholinomethyl)-1H-indole-2-carboxamide | 473257-41-9

• 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: 5-chloro-3-(3,5-dimethylphenylsulfonyl)-4-fluoro-N-(morpholinomethyl)-1H-indole-2-carboxamide
• 英文别名: 5-chloro-4-fluoro-3-(3,5-dimethylphenylsulfonyl)-indole-2-(1-morpholinomethyl)-carboxamide；5-chloro-3-(3,5-dimethylphenyl)sulfonyl-4-fluoro-N-(morpholinomethyl)-1H-indole-2-carboxamide；5-chloro-3-(3,5-dimethylphenyl)sulfonyl-4-fluoro-N-(morpholin-4-ylmethyl)-1H-indole-2-carboxamide
• CAS: 473257-41-9
• 化学式: C₂₂H₂₃ClFN₃O₄S
• 分子量: 479.96
• InChiKey: MRLOZCSRZCFVID-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  99.9
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  吗啉 、 5-chloro-3-[(3,5-dimethylphenyl)sulfonyl]-4-fluoro-1H-indole-2-carboxamide 、 聚合甲醛 以 苯 为溶剂， 反应 3.0h， 以69%的产率得到5-chloro-3-(3,5-dimethylphenylsulfonyl)-4-fluoro-N-(morpholinomethyl)-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

文献信息

• Phenylindoles for the treatment of HIV
  申请人：LaColla Paulo

  公开号：US20070293668A1

  公开（公告）日：2007-12-20

  The invention as disclosed herein is a method and composition for the treatment of HIV in humans and other host animals, that includes the administration of an effective HIV treatment amount of a phenylindole as described herein or a pharmaceutically acceptable salt or prodrug thereof, optionally in a pharmaceutically acceptable carrier. The compounds of this invention either possess antiviral (i.e., anti-HIV) activity, or are metabolized to a compound that exhibits such activity.

  本发明公开了一种用于治疗人类和其他宿主动物HIV的方法和组合物，包括给予所述的苯基吲哚或其药学上可接受的盐或前药的有效HIV治疗剂量，可选地在药学上可接受的载体中。本发明的化合物具有抗病毒（即抗HIV）活性，或代谢为表现出这种活性的化合物。
• 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.