(2S,3S)-N-[(1R)-1-[dihydroxy(methyl)silyl]-3-methylbutyl]-3-methyl-2-[(2-naphthalen-2-ylacetyl)amino]pentanamide | 1393926-72-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2S,3S)-N-[(1R)-1-[dihydroxy(methyl)silyl]-3-methylbutyl]-3-methyl-2-[(2-naphthalen-2-ylacetyl)amino]pentanamide
• CAS: 1393926-72-1
• 化学式: C₂₄H₃₆N₂O₄Si
• 分子量: 444.646
• InChiKey: FOTYGPLESIQEOI-IMRHEYAYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.04
• 重原子数：
  31
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  98.7
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2S,3S)-N-[(1R)-1-[dihydroxy(methyl)silyl]-3-methylbutyl]-3-methyl-2-[(2-naphthalen-2-ylacetyl)amino]pentanamide 在 氢氟酸 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 0.5h， 以15.6 mg的产率得到(2S,3S)-N-((R)-1-(difluoro(methyl)silyl)-3-methylbutyl)-3-methyl-2-(2-(naphthalen-2-yl)acetamido)pentanamide
  参考文献：
  名称：

  Synthesis and Evaluation of Silanediols as Highly Selective Uncompetitive Inhibitors of Human Neutrophil Elastase

  摘要：

  Chronic obstructive pulmonary disease (COPD) is an increasing health problem and is estimated to be the fifth leading cause of death in 2020 according to the World Health Organization. Current treatments are only palliative, and therefore the development of new medicine for the treatment of COPD is urgent. Human Neutrophil Elastase (HNE) is a serine protease that is heavily involved in the progression of COPD through inflammatory breakdown of lung tissue. Consequently, inhibitors of HNE are of great interest as therapeutics. In this article, the development of silanediol peptide isosters as inhibitors of HNE is presented. Kinetic studies revealed that incorporation of a silanediol isoster in the inhibitor structure resulted in an uncompetitive mechanism of inhibition, which further resulted in excellent selectivity. The peculiar mechanism of inhibition and the resulting selectivity makes the presented inhibitors promising leads for the development of new FINE-inhibitor-based therapeutics for the treatment of COPD.

  DOI：

  10.1021/jm301000k
• 作为产物：
  描述：

  (R)-2-methyl-N-((R)-3-methyl-1-(methyl-di-p-tolylsilyl)butyl)propane-2-sulfinamide 在 N-甲基吗啉 、 盐酸 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 86.0h， 生成 (2S,3S)-N-[(1R)-1-[dihydroxy(methyl)silyl]-3-methylbutyl]-3-methyl-2-[(2-naphthalen-2-ylacetyl)amino]pentanamide
  参考文献：
  名称：

  Synthesis and Evaluation of Silanediols as Highly Selective Uncompetitive Inhibitors of Human Neutrophil Elastase

  摘要：

  Chronic obstructive pulmonary disease (COPD) is an increasing health problem and is estimated to be the fifth leading cause of death in 2020 according to the World Health Organization. Current treatments are only palliative, and therefore the development of new medicine for the treatment of COPD is urgent. Human Neutrophil Elastase (HNE) is a serine protease that is heavily involved in the progression of COPD through inflammatory breakdown of lung tissue. Consequently, inhibitors of HNE are of great interest as therapeutics. In this article, the development of silanediol peptide isosters as inhibitors of HNE is presented. Kinetic studies revealed that incorporation of a silanediol isoster in the inhibitor structure resulted in an uncompetitive mechanism of inhibition, which further resulted in excellent selectivity. The peculiar mechanism of inhibition and the resulting selectivity makes the presented inhibitors promising leads for the development of new FINE-inhibitor-based therapeutics for the treatment of COPD.

  DOI：

  10.1021/jm301000k

文献信息

• Synthesis and Evaluation of Silanediols as Highly Selective Uncompetitive Inhibitors of Human Neutrophil Elastase
  作者：Julie L. H. Madsen、Thomas L. Andersen、Salvatore Santamaria、Hideaki Nagase、Jan J. Enghild、Troels Skrydstrup

  DOI：10.1021/jm301000k

  日期：2012.9.13

  Chronic obstructive pulmonary disease (COPD) is an increasing health problem and is estimated to be the fifth leading cause of death in 2020 according to the World Health Organization. Current treatments are only palliative, and therefore the development of new medicine for the treatment of COPD is urgent. Human Neutrophil Elastase (HNE) is a serine protease that is heavily involved in the progression of COPD through inflammatory breakdown of lung tissue. Consequently, inhibitors of HNE are of great interest as therapeutics. In this article, the development of silanediol peptide isosters as inhibitors of HNE is presented. Kinetic studies revealed that incorporation of a silanediol isoster in the inhibitor structure resulted in an uncompetitive mechanism of inhibition, which further resulted in excellent selectivity. The peculiar mechanism of inhibition and the resulting selectivity makes the presented inhibitors promising leads for the development of new FINE-inhibitor-based therapeutics for the treatment of COPD.