tert-butyl ((2S,3R)-3-(tert-butoxy)-1-oxo-1-(7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydroisoquinoline-2-sulfonamido)butan-2-yl)carbamate | 1422970-26-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: tert-butyl ((2S,3R)-3-(tert-butoxy)-1-oxo-1-(7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydroisoquinoline-2-sulfonamido)butan-2-yl)carbamate
• 英文别名: tert-butyl N-[(2S,3R)-3-[(2-methylpropan-2-yl)oxy]-1-oxo-1-[[7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydro-1H-isoquinolin-2-yl]sulfonylamino]butan-2-yl]carbamate
• CAS: 1422970-26-0
• 化学式: C₂₈H₄₆BN₃O₈S
• 分子量: 595.566
• InChiKey: RDRNIIQNEJCOQO-GCJKJVERSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  41
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  141
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  tert-butyl ((2S,3R)-3-(tert-butoxy)-1-oxo-1-(7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydroisoquinoline-2-sulfonamido)butan-2-yl)carbamate 在 盐酸 、 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 生成 (2S,3R)-N-((7-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-3,4-dihydroisoquinolin-2(1H)-yl)sulfonyl)-2-amino-3-hydroxybutanamide hydrochloride
  参考文献：
  名称：

  Identification of Bacteria-Selective Threonyl-tRNA Synthetase Substrate Inhibitors by Structure-Based Design

  摘要：

  A series of potent and bacteria-selective threonyl-tRNA synthetase (ThrRS) inhibitors have been identified using structure-based drug design. These compounds occupied the substrate binding site of ThrRS and showed excellent binding affinities for all of the bacterial orthologues tested. Some of the compounds displayed greatly improved bacterial selectivity. Key residues responsible for potency and bacteria/human ThrRS selectivity have been identified. Antimicrobial activity has been achieved against wild-type Haemophilus influenzae and efflux-deficient mutants of Escherichia coli and Burkholderia thailandensis.

  DOI：

  10.1021/jm301756m
• 作为产物：
  描述：

  7-溴-1,2,3,4-四氢异喹啉 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 potassium acetate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 、 N,N-二甲基乙酰胺 、 N,N-二甲基甲酰胺 为溶剂， 反应 29.0h， 生成 tert-butyl ((2S,3R)-3-(tert-butoxy)-1-oxo-1-(7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydroisoquinoline-2-sulfonamido)butan-2-yl)carbamate
  参考文献：
  名称：

  Identification of Bacteria-Selective Threonyl-tRNA Synthetase Substrate Inhibitors by Structure-Based Design

  摘要：

  A series of potent and bacteria-selective threonyl-tRNA synthetase (ThrRS) inhibitors have been identified using structure-based drug design. These compounds occupied the substrate binding site of ThrRS and showed excellent binding affinities for all of the bacterial orthologues tested. Some of the compounds displayed greatly improved bacterial selectivity. Key residues responsible for potency and bacteria/human ThrRS selectivity have been identified. Antimicrobial activity has been achieved against wild-type Haemophilus influenzae and efflux-deficient mutants of Escherichia coli and Burkholderia thailandensis.

  DOI：

  10.1021/jm301756m

文献信息

• Identification of Bacteria-Selective Threonyl-tRNA Synthetase Substrate Inhibitors by Structure-Based Design
  作者：Min Teng、Mark T. Hilgers、Mark L. Cunningham、Allen Borchardt、Jeffrey B. Locke、Sunny Abraham、Gregory Haley、Bryan P. Kwan、Courtney Hall、Grayson W. Hough、Karen J. Shaw、John Finn

  DOI：10.1021/jm301756m

  日期：2013.2.28

  A series of potent and bacteria-selective threonyl-tRNA synthetase (ThrRS) inhibitors have been identified using structure-based drug design. These compounds occupied the substrate binding site of ThrRS and showed excellent binding affinities for all of the bacterial orthologues tested. Some of the compounds displayed greatly improved bacterial selectivity. Key residues responsible for potency and bacteria/human ThrRS selectivity have been identified. Antimicrobial activity has been achieved against wild-type Haemophilus influenzae and efflux-deficient mutants of Escherichia coli and Burkholderia thailandensis.