(S,S)-N-(4-phenylbenzoyl)-3-bromophenylalanyl-O-((1-(methoxycarbonylmethyl)-1H-1,2,3-triazol-4-yl)methyl)serine nitrile

• 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: (S,S)-N-(4-phenylbenzoyl)-3-bromophenylalanyl-O-((1-(methoxycarbonylmethyl)-1H-1,2,3-triazol-4-yl)methyl)serine nitrile
• 英文别名: methyl 2-[4-[[(2R)-2-[[(2S)-3-(3-bromophenyl)-2-[(4-phenylbenzoyl)amino]propanoyl]amino]-2-cyanoethoxy]methyl]triazol-1-yl]acetate
• 化学式: C₃₁H₂₉BrN₆O₅
• 分子量: 645.512
• InChiKey: ANZFZARZEQENJQ-IAPPQJPRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  43
• 可旋转键数：
  14
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  148
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (S)-2-[(tert-butoxycarbonyl)amino]-3-(prop-2-yn-1-yloxy)propanoic acid 在 N-甲基吗啉 、 三聚氯氰 、 copper(ll) sulfate pentahydrate 、 sodium ascorbate 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.84h， 生成 (S,S)-N-(4-phenylbenzoyl)-3-bromophenylalanyl-O-((1-(methoxycarbonylmethyl)-1H-1,2,3-triazol-4-yl)methyl)serine nitrile
  参考文献：
  名称：

  Cathepsin B Inhibitors: Combining Dipeptide Nitriles with an Occluding Loop Recognition Element by Click Chemistry

  摘要：

  An active site mapping of human cathepsin B with dipeptide nitrile inhibitors was performed for a combinatorial approach by introducing several points of diversity and stepwise optimizing the inhibitor structure. To address the occluding loop of cathepsin B by a carboxylate moiety, click chemistry to generate linker-connected molecules was applied. Inhibitor 17 exhibited K-i values of 41.3 nM, 27.3 nM, or 19.2 nM, depending on the substrate and pH of the assay. Kinetic data were discussed with respect to the conformational selection and induced fit models.

  DOI：

  10.1021/acsmedchemlett.5b00474

文献信息

• Cathepsin B Inhibitors: Combining Dipeptide Nitriles with an Occluding Loop Recognition Element by Click Chemistry
  作者：Janina Schmitz、Tianwei Li、Ulrike Bartz、Michael Gütschow

  DOI：10.1021/acsmedchemlett.5b00474

  日期：2016.3.10

  An active site mapping of human cathepsin B with dipeptide nitrile inhibitors was performed for a combinatorial approach by introducing several points of diversity and stepwise optimizing the inhibitor structure. To address the occluding loop of cathepsin B by a carboxylate moiety, click chemistry to generate linker-connected molecules was applied. Inhibitor 17 exhibited K-i values of 41.3 nM, 27.3 nM, or 19.2 nM, depending on the substrate and pH of the assay. Kinetic data were discussed with respect to the conformational selection and induced fit models.