(R)-2-(tert-butoxycarbonyl)-6-fluoro-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid | 444892-16-4

• 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: (R)-2-(tert-butoxycarbonyl)-6-fluoro-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid
• 英文别名: (3R)-2-[(tert-butoxy)carbonyl]-6-fluoro-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid；(3R)-6-fluoro-2-[(2-methylpropan-2-yl)oxycarbonyl]-3,4-dihydro-1H-isoquinoline-3-carboxylic acid
• CAS: 444892-16-4
• 化学式: C₁₅H₁₈FNO₄
• 分子量: 295.311
• InChiKey: RPIVJWKAEDUERE-GFCCVEGCSA-N

物化性质

• 沸点：
  433.6±45.0 °C(Predicted)
• 密度：
  1.278±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-溴-2-(2-(二甲氨基)乙氧基)苯胺 、 (R)-2-(tert-butoxycarbonyl)-6-fluoro-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 tert-butyl (3R)-3-[[4-bromo-2-[2-(dimethylamino)ethoxy]phenyl]carbamoyl]-6-fluoro-3,4-dihydro-1H-isoquinoline-2-carboxylate
  参考文献：
  名称：

  Tetrahydroisoquinoline Derivatives As Highly Selective and Potent Rho Kinase Inhibitors

  摘要：

  Rho kinase (ROCK) is a promising drug target for the treatment of many diseases including hypertension, multiple sclerosis, cancer, and glaucoma. The structure-activity relationships (SAR) around a series of tetrahydroisoquinolines were evaluated utilizing biochemical and cell-based assays to measure ROCK inhibition. These novel ROCK inhibitors possess high potency, high selectivity, and appropriate pharmacokinetic properties for glaucoma applications. The lead compound, 35, had subnanomolar potency in enzyme ROCK-II assays as well as excellent cell-based potency (IC(50) = 51 nM). In a kinase panel profiling, 35 had an off-target hit rate of only 1.6% against 442 kinases. Pharmacology studies showed that compound 35 was efficacious in reducing intraocular pressure (IOP) in rats with reasonably long duration of action. These results suggest that compound 35 may serve as a promising agent for further development in the treatment of glaucoma.

  DOI：

  10.1021/jm100579r
• 作为产物：
  描述：

  二碳酸二叔丁酯 、 (R)-6-fluoro-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid hydrochloride 在 sodium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 2.0h， 生成 (R)-2-(tert-butoxycarbonyl)-6-fluoro-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid
  参考文献：
  名称：

  Tetrahydroisoquinoline Derivatives As Highly Selective and Potent Rho Kinase Inhibitors

  摘要：

  Rho kinase (ROCK) is a promising drug target for the treatment of many diseases including hypertension, multiple sclerosis, cancer, and glaucoma. The structure-activity relationships (SAR) around a series of tetrahydroisoquinolines were evaluated utilizing biochemical and cell-based assays to measure ROCK inhibition. These novel ROCK inhibitors possess high potency, high selectivity, and appropriate pharmacokinetic properties for glaucoma applications. The lead compound, 35, had subnanomolar potency in enzyme ROCK-II assays as well as excellent cell-based potency (IC(50) = 51 nM). In a kinase panel profiling, 35 had an off-target hit rate of only 1.6% against 442 kinases. Pharmacology studies showed that compound 35 was efficacious in reducing intraocular pressure (IOP) in rats with reasonably long duration of action. These results suggest that compound 35 may serve as a promising agent for further development in the treatment of glaucoma.

  DOI：

  10.1021/jm100579r

文献信息

• Tetrahydroisoquinoline Derivatives As Highly Selective and Potent Rho Kinase Inhibitors
  作者：Xingang Fang、Yan Yin、Yen Ting Chen、Lei Yao、Bo Wang、Michael D. Cameron、Li Lin、Susan Khan、Claudia Ruiz、Thomas Schröter、Wayne Grant、Amiee Weiser、Jennifer Pocas、Alok Pachori、Stephan Schürer、Philip LoGrasso、Yangbo Feng

  DOI：10.1021/jm100579r

  日期：2010.8.12

  Rho kinase (ROCK) is a promising drug target for the treatment of many diseases including hypertension, multiple sclerosis, cancer, and glaucoma. The structure-activity relationships (SAR) around a series of tetrahydroisoquinolines were evaluated utilizing biochemical and cell-based assays to measure ROCK inhibition. These novel ROCK inhibitors possess high potency, high selectivity, and appropriate pharmacokinetic properties for glaucoma applications. The lead compound, 35, had subnanomolar potency in enzyme ROCK-II assays as well as excellent cell-based potency (IC(50) = 51 nM). In a kinase panel profiling, 35 had an off-target hit rate of only 1.6% against 442 kinases. Pharmacology studies showed that compound 35 was efficacious in reducing intraocular pressure (IOP) in rats with reasonably long duration of action. These results suggest that compound 35 may serve as a promising agent for further development in the treatment of glaucoma.