3-bromomethyl-4-(tert-butyl-dimethyl-silanoxy)-indazole-1-carboxylic acid tert-butyl ester | 293758-73-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: 3-bromomethyl-4-(tert-butyl-dimethyl-silanoxy)-indazole-1-carboxylic acid tert-butyl ester
• 英文别名: 1h-Indazole-1-carboxylic acid,3-(bromomethyl)-4-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-,1,1-dimethylethyl ester；tert-butyl 3-(bromomethyl)-4-[tert-butyl(dimethyl)silyl]oxyindazole-1-carboxylate
• CAS: 293758-73-3
• 化学式: C₁₉H₂₉BrN₂O₃Si
• 分子量: 441.44
• InChiKey: CYDDNLQJHKZPEF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  53.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-bromomethyl-4-(tert-butyl-dimethyl-silanoxy)-indazole-1-carboxylic acid tert-butyl ester 在 potassium fluoride 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.0h， 生成 7-[4-(4-tert-Butyl-benzyloxy)-1H-indazol-3-ylmethylsulfanyl]-4-methyl-chromen-2-one
  参考文献：
  名称：

  Novel Inhibitors of DNA Gyrase:  3D Structure Based Biased Needle Screening, Hit Validation by Biophysical Methods, and 3D Guided Optimization. A Promising Alternative to Random Screening

  摘要：

  Random screening provided no suitable lead structures in a search for novel inhibitors of the bacterial enzyme DNA gyrase. Therefore, an alternative approach had to be developed. Relying on the detailed 3D structural information of the targeted ATP binding site, our approach combines as key techniques (1) an in silico screening for potential low molecular weight inhibitors, (2) a biased high throughput DNA gyrase screen, (3) validation of the screening hits by biophysical methods, and (4) a 3D guided optimization process. When the in silico screening was performed, the initial data set containing 350 000 compounds could be reduced to 3000 molecules. Testing these 3000 selected compounds in the DNA gyrase assay provided 150 hits clustered in 14 classes. Seven classes could be validated as true, novel DNA gyrase inhibitors that act by binding to the ATP binding site located on subunit B: phenols, 2-amino-triazines, 4-amino-pyrimidines, 2-amino-pyrimidines, pyrrolopyrimidines, indazoles, and 2-hydroxymethyl-indoles. The 3D guided optimization provided highly potent DNA gyrase inhibitors, e.g., the 3,4-disubstituted indazole 23 being a 10 times more potent DNA gyrase inhibitor than novobiocin (3).

  DOI：

  10.1021/jm000017s
• 作为产物：
  描述：

  2,6-二羟基苯乙酮 在 N-溴代丁二酰亚胺(NBS) 、 一水合肼 、 三乙胺 、 过氧化苯甲酰 作用下， 以 四氯化碳 、 乙二醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 21.5h， 生成 3-bromomethyl-4-(tert-butyl-dimethyl-silanoxy)-indazole-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Novel Inhibitors of DNA Gyrase:  3D Structure Based Biased Needle Screening, Hit Validation by Biophysical Methods, and 3D Guided Optimization. A Promising Alternative to Random Screening

  摘要：

  Random screening provided no suitable lead structures in a search for novel inhibitors of the bacterial enzyme DNA gyrase. Therefore, an alternative approach had to be developed. Relying on the detailed 3D structural information of the targeted ATP binding site, our approach combines as key techniques (1) an in silico screening for potential low molecular weight inhibitors, (2) a biased high throughput DNA gyrase screen, (3) validation of the screening hits by biophysical methods, and (4) a 3D guided optimization process. When the in silico screening was performed, the initial data set containing 350 000 compounds could be reduced to 3000 molecules. Testing these 3000 selected compounds in the DNA gyrase assay provided 150 hits clustered in 14 classes. Seven classes could be validated as true, novel DNA gyrase inhibitors that act by binding to the ATP binding site located on subunit B: phenols, 2-amino-triazines, 4-amino-pyrimidines, 2-amino-pyrimidines, pyrrolopyrimidines, indazoles, and 2-hydroxymethyl-indoles. The 3D guided optimization provided highly potent DNA gyrase inhibitors, e.g., the 3,4-disubstituted indazole 23 being a 10 times more potent DNA gyrase inhibitor than novobiocin (3).

  DOI：

  10.1021/jm000017s

文献信息

• Novel Inhibitors of DNA Gyrase:  3D Structure Based Biased Needle Screening, Hit Validation by Biophysical Methods, and 3D Guided Optimization. A Promising Alternative to Random Screening
  作者：Hans-Joachim Boehm、Markus Boehringer、Daniel Bur、Hans Gmuender、Walter Huber、Werner Klaus、Dirk Kostrewa、Holger Kuehne、Thomas Luebbers、Nathalie Meunier-Keller、Francis Mueller

  DOI：10.1021/jm000017s

  日期：2000.7.1

  Random screening provided no suitable lead structures in a search for novel inhibitors of the bacterial enzyme DNA gyrase. Therefore, an alternative approach had to be developed. Relying on the detailed 3D structural information of the targeted ATP binding site, our approach combines as key techniques (1) an in silico screening for potential low molecular weight inhibitors, (2) a biased high throughput DNA gyrase screen, (3) validation of the screening hits by biophysical methods, and (4) a 3D guided optimization process. When the in silico screening was performed, the initial data set containing 350 000 compounds could be reduced to 3000 molecules. Testing these 3000 selected compounds in the DNA gyrase assay provided 150 hits clustered in 14 classes. Seven classes could be validated as true, novel DNA gyrase inhibitors that act by binding to the ATP binding site located on subunit B: phenols, 2-amino-triazines, 4-amino-pyrimidines, 2-amino-pyrimidines, pyrrolopyrimidines, indazoles, and 2-hydroxymethyl-indoles. The 3D guided optimization provided highly potent DNA gyrase inhibitors, e.g., the 3,4-disubstituted indazole 23 being a 10 times more potent DNA gyrase inhibitor than novobiocin (3).