N-(phenylcarbamoyl)-leucyl-methylazaalanine-nitrile | 1259945-85-1

• 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: N-(phenylcarbamoyl)-leucyl-methylazaalanine-nitrile
• 英文别名: 1-[(2S)-1-[[cyano(methyl)amino]-methylamino]-4-methyl-1-oxopentan-2-yl]-3-phenylurea
• CAS: 1259945-85-1
• 化学式: C₁₆H₂₃N₅O₂
• 分子量: 317.391
• InChiKey: CLOALCKDNZPWBO-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  88.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  L-亮氨酸叔丁酯盐酸盐 在 N-甲基吗啉 、 sodium acetate 、 N,N-二异丙基乙胺 、 三氟乙酸 、 sodium hydroxide 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 92.0h， 生成 N-(phenylcarbamoyl)-leucyl-methylazaalanine-nitrile
  参考文献：
  名称：

  Structural Optimization of Azadipeptide Nitriles Strongly Increases Association Rates and Allows the Development of Selective Cathepsin Inhibitors

  摘要：

  Using the example of cathepsin K, we demonstrate the design of highly potent and selective azadipeptide nitrite inhibitors A systematic scan with respect to P2 and P3 substituents was carried out Structural modifications strongly affected the enzyme-inhibitor association (but not dissociation) rate A combination of optimized P2 and P3 substituents with a methylation of the P3-P2 amide linker resulted in the picomolar cathepsin K inhibitor 19 with remarkable selectivity over cathepsins L, B, and S

  DOI：

  10.1021/jm101272p

文献信息

• Structural Optimization of Azadipeptide Nitriles Strongly Increases Association Rates and Allows the Development of Selective Cathepsin Inhibitors
  作者：Maxim Frizler、Friederike Lohr、Norbert Furtmann、Julia Kläs、Michael Gütschow

  DOI：10.1021/jm101272p

  日期：2011.1.13

  Using the example of cathepsin K, we demonstrate the design of highly potent and selective azadipeptide nitrite inhibitors A systematic scan with respect to P2 and P3 substituents was carried out Structural modifications strongly affected the enzyme-inhibitor association (but not dissociation) rate A combination of optimized P2 and P3 substituents with a methylation of the P3-P2 amide linker resulted in the picomolar cathepsin K inhibitor 19 with remarkable selectivity over cathepsins L, B, and S