[1-(3-nitrobenzyl)-1H-indol-3-yl]acetic acid | 1542273-90-4

• 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: [1-(3-nitrobenzyl)-1H-indol-3-yl]acetic acid
• 英文别名: 2-[1-[(3-Nitrophenyl)methyl]indol-3-yl]acetic acid
• CAS: 1542273-90-4
• 化学式: C₁₇H₁₄N₂O₄
• 分子量: 310.309
• InChiKey: ACYMPHZSMJTWEL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  88
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [1-(3-nitrobenzyl)-1H-indol-3-yl]acetic acid 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 反应 4.0h， 以84%的产率得到[1-(3-aminobenzyl)-1H-indol-3-yl]acetic acid
  参考文献：
  名称：

  Integrated Strategies for Identifying Leads That Target the NS3 Helicase of the Hepatitis C Virus

  摘要：

  Future treatments for individuals infected by the hepatitis C virus (HCV) will likely involve combinations of compounds that inhibit multiple viral targets. The helicase of HCV is an attractive target with no known drug candidates in clinical trials. Herein we describe an integrated strategy for identifying fragment inhibitors using structural and biophysical techniques. Based on an X-ray structure of apo HCV helicase and in silico and bioinformatic analyses of HCV variants, we identified that one site in particular (labeled 3 + 4) was the most conserved and attractive pocket to target for a drug discovery campaign. Compounds from multiple sources were screened to identify inhibitors or binders to this site, and enzymatic and biophysical assays (NMR and SPR) were used to triage the most promising ligands for 3D structure determination by X-ray crystallography. Medicinal chemistry and biophysical evaluations focused on exploring the most promising lead series. The strategies employed here can have general utility in drug discovery.

  DOI：

  10.1021/jm401432c
• 作为产物：
  描述：

  3-吲哚乙酸 、 3-硝基溴苄 在 sodium hexamethyldisilazane 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以3%的产率得到[1-(3-nitrobenzyl)-1H-indol-3-yl]acetic acid
  参考文献：
  名称：

  Integrated Strategies for Identifying Leads That Target the NS3 Helicase of the Hepatitis C Virus

  摘要：

  Future treatments for individuals infected by the hepatitis C virus (HCV) will likely involve combinations of compounds that inhibit multiple viral targets. The helicase of HCV is an attractive target with no known drug candidates in clinical trials. Herein we describe an integrated strategy for identifying fragment inhibitors using structural and biophysical techniques. Based on an X-ray structure of apo HCV helicase and in silico and bioinformatic analyses of HCV variants, we identified that one site in particular (labeled 3 + 4) was the most conserved and attractive pocket to target for a drug discovery campaign. Compounds from multiple sources were screened to identify inhibitors or binders to this site, and enzymatic and biophysical assays (NMR and SPR) were used to triage the most promising ligands for 3D structure determination by X-ray crystallography. Medicinal chemistry and biophysical evaluations focused on exploring the most promising lead series. The strategies employed here can have general utility in drug discovery.

  DOI：

  10.1021/jm401432c

文献信息

• Integrated Strategies for Identifying Leads That Target the NS3 Helicase of the Hepatitis C Virus
  作者：Steven R. LaPlante、Anil K. Padyana、Asitha Abeywardane、Pierre Bonneau、Mireille Cartier、René Coulombe、Araz Jakalian、Jessi Wildeson-Jones、Xiang Li、Shuang Liang、Ginette McKercher、Peter White、Qiang Zhang、Steven J. Taylor

  DOI：10.1021/jm401432c

  日期：2014.3.13

  Future treatments for individuals infected by the hepatitis C virus (HCV) will likely involve combinations of compounds that inhibit multiple viral targets. The helicase of HCV is an attractive target with no known drug candidates in clinical trials. Herein we describe an integrated strategy for identifying fragment inhibitors using structural and biophysical techniques. Based on an X-ray structure of apo HCV helicase and in silico and bioinformatic analyses of HCV variants, we identified that one site in particular (labeled 3 + 4) was the most conserved and attractive pocket to target for a drug discovery campaign. Compounds from multiple sources were screened to identify inhibitors or binders to this site, and enzymatic and biophysical assays (NMR and SPR) were used to triage the most promising ligands for 3D structure determination by X-ray crystallography. Medicinal chemistry and biophysical evaluations focused on exploring the most promising lead series. The strategies employed here can have general utility in drug discovery.