ethyl 5-chloro-4-fluoro-3-[(3,5-dimethylphenyl)sulfonyl]-1H-indole-2-carboxylate | 473257-80-6

• 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: ethyl 5-chloro-4-fluoro-3-[(3,5-dimethylphenyl)sulfonyl]-1H-indole-2-carboxylate
• 英文别名: ethyl 5-chloro-3-[(3,5-dimethylphenyl)sulfonyl]-4-fluoro-1Hindole-2-carboxylate；ethyl 5-chloro-3-[(3,5-dimethylphenyl)sulfonyl]-1H-indole-2-carboxylate；Ethyl 5-chloro-3-(3,5-dimethylphenylsulfonyl)-4-fluoroindole-2-carboxylate；ethyl 5-chloro-3-(3,5-dimethylphenyl)sulfonyl-4-fluoro-1H-indole-2-carboxylate
• CAS: 473257-80-6
• 化学式: C₁₉H₁₇ClFNO₄S
• 分子量: 409.866
• InChiKey: NPFREKZWZANWSL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  84.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 5-chloro-4-fluoro-3-[(3,5-dimethylphenyl)sulfonyl]-1H-indole-2-carboxylate 以 乙醇 为溶剂， 以89%的产率得到ethyl 5,7-difluoro-3-[(3,5-dimethylphenyl)sulfonyl]-1H-indole-2-carboxylate
  参考文献：
  名称：

  Phenylindoles for the treatment of HIV

  摘要：

  本发明公开了一种用于治疗人类和其他宿主动物体内的HIV的方法和组合物，包括根据本文所述的给予有效的HIV治疗量的苯基吲哚或其药学上可接受的盐或前药，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，或者经代谢后形成具有该活性的化合物。

  公开号：

  US20020193415A1
• 作为产物：
  描述：

  ethyl 5-chloro-4-fluoro-3-[(3,5-dimethylphenyl)thio]-1H-indole-2-carboxylate 在 间氯过氧苯甲酸 作用下， 以 氯仿 为溶剂， 反应 1.5h， 以59%的产率得到ethyl 5-chloro-4-fluoro-3-[(3,5-dimethylphenyl)sulfonyl]-1H-indole-2-carboxylate
  参考文献：
  名称：

  Indolyl Aryl Sulfones as HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors:  Role of Two Halogen Atoms at the Indole Ring in Developing New Analogues with Improved Antiviral Activity

  摘要：

  Indolyl aryl sulfones bearing the 4,5-difluoro (10) or 5-chloro-4-fluoro (16) substitution pattern at the indole ring were potent inhibitors of HIV-1 WT and the NNRTI-resistant strains Y181C and K103N-Y181C. These compounds were highly effective against the 112 and the AB1 strains in lymphocytes and inhibited at nanomolar concentration the multiplication of the IIIBBa-L strain in macrophages. Compound 16 was exceptionally potent against RT WT and RTs carrying the K103N, Y181I, and L100I mutations.

  DOI：

  10.1021/jm070488f

文献信息

• Indolyl Aryl Sulfones as HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors:  Role of Two Halogen Atoms at the Indole Ring in Developing New Analogues with Improved Antiviral Activity
  作者：Giuseppe La Regina、Antonio Coluccia、Francesco Piscitelli、Alberto Bergamini、Anna Sinistro、Antonella Cavazza、Giovanni Maga、Alberta Samuele、Samantha Zanoli、Ettore Novellino、Marino Artico、Romano Silvestri

  DOI：10.1021/jm070488f

  日期：2007.10.1

  Indolyl aryl sulfones bearing the 4,5-difluoro (10) or 5-chloro-4-fluoro (16) substitution pattern at the indole ring were potent inhibitors of HIV-1 WT and the NNRTI-resistant strains Y181C and K103N-Y181C. These compounds were highly effective against the 112 and the AB1 strains in lymphocytes and inhibited at nanomolar concentration the multiplication of the IIIBBa-L strain in macrophages. Compound 16 was exceptionally potent against RT WT and RTs carrying the K103N, Y181I, and L100I mutations.
• 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.
• PHENYLINDOLES FOR THE TREATMENT OF HIV
  申请人：Idenix (Cayman) Limited

  公开号：EP1390029A1

  公开（公告）日：2004-02-25
• EP1390029A4
  申请人：——

  公开号：EP1390029A4

  公开（公告）日：2005-11-30
• US6710068B2
  申请人：——

  公开号：US6710068B2

  公开（公告）日：2004-03-23