4-(tert-butyl-dimethyl-silanoxy)-3-methyl-1H-indazole | 293758-71-1

• 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: 4-(tert-butyl-dimethyl-silanoxy)-3-methyl-1H-indazole
• 英文别名: 4-(tert-butyl-dimethyl-silanyloxy)-3-methyl-1H-indazole；4-(tert-butyl-dimethylsilanyloxy)-3-methyl-1H-indazole；tert-butyl-dimethyl-[(3-methyl-2H-indazol-4-yl)oxy]silane
• CAS: 293758-71-1
• 化学式: C₁₄H₂₂N₂OSi
• 分子量: 262.427
• InChiKey: CPUQFASWPYZRAJ-UHFFFAOYSA-N

物化性质

• 沸点：
  340.0±22.0 °C(Predicted)
• 密度：
  1.034±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.26
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  37.9
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-(tert-butyl-dimethyl-silanoxy)-3-methyl-1H-indazole 在 N-溴代丁二酰亚胺(NBS) 、 三乙胺 、 过氧化苯甲酰 作用下， 以 四氯化碳 、 二氯甲烷 、 乙腈 为溶剂， 反应 11.5h， 生成 4-(tert-butyl-dimethyl-silanyloxy)-3-(4-methylcoumarin-7-ylsulfanylmethyl)-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
• 作为产物：
  描述：

  2,6-二羟基苯乙酮 在 咪唑 、 肼 作用下， 以 乙二醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.3h， 生成 4-(tert-butyl-dimethyl-silanoxy)-3-methyl-1H-indazole
  参考文献：
  名称：

  Antifungal Triazole Derivatives

  摘要：

  本文揭示了抗真菌三唑衍生物或其药用盐，其制备方法，以及包含它们的药物组合物。

  公开号：

  US20080194661A1

文献信息

• Antifungal Triazole Derivatives
  申请人：Park Joon Seok

  公开号：US20080194661A1

  公开（公告）日：2008-08-14

  Disclosed herein are antifungal triazole derivatives or pharmaceutically acceptable salts thereof, a preparation method thereof, and a pharmaceutical composition comprising the same.

  本文揭示了抗真菌三唑衍生物或其药用盐，其制备方法，以及包含它们的药物组合物。
• Antifungal triazole derivatives
  申请人：Daewoong Pharmaceutical Co., Ltd.

  公开号：US07812045B2

  公开（公告）日：2010-10-12

  Disclosed herein are antifungal triazole derivatives or pharmaceutically acceptable salts thereof, a preparation method thereof, and a pharmaceutical composition comprising the same.

  本文揭示了抗真菌三唑衍生物或其药学上可接受的盐，其制备方法以及包含其的制药组合物。
• [EN] SUBSTITUTED INDAZOLE-O-GLUCOSIDES<br/>[FR] INDAZOLES-O-GLUCOSIDES SUBSTITUES
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2005011592A3

  公开（公告）日：2005-06-16
• WO2006/109933
  申请人：——

  公开号：——

  公开（公告）日：——
• 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).