(2S,4R)-tert-butyl 4-azido-2-(pyrrolidine-1-carbonyl)pyrrolidine-1-carboxylate | 1407969-39-4

• 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,4R)-tert-butyl 4-azido-2-(pyrrolidine-1-carbonyl)pyrrolidine-1-carboxylate
• 英文别名: tert-butyl (2S,4R)-4-azido-2-(pyrrolidine-1-carbonyl)pyrrolidine-1-carboxylate
• CAS: 1407969-39-4
• 化学式: C₁₄H₂₃N₅O₃
• 分子量: 309.368
• InChiKey: IPPUAXLVJZRYJB-MNOVXSKESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  64.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2S,4R)-tert-butyl 4-azido-2-(pyrrolidine-1-carbonyl)pyrrolidine-1-carboxylate 在 copper(l) iodide 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 26.75h， 生成 4-phenyl-1-[(2S,4R)-4-(4-phenyltriazol-1-yl)-2-(pyrrolidine-1-carbonyl)pyrrolidin-1-yl]butan-1-one
  参考文献：
  名称：

  P2-Substituted N-Acylprolylpyrrolidine Inhibitors of Prolyl Oligopeptidase: Biochemical Evaluation, Binding Mode Determination, and Assessment in a Cellular Model of Synucleinopathy

  摘要：

  We have investigated the effect of regiospecifically , introducing substituents in the P2 part of the typical dipeptide derived basic structure of PREP inhibitors. This hitherto unexplored modification type can be used to improve target affinity, selectivity, and physicochemical parameters in drug discovery programs focusing on PREP inhibitors. Biochemical evaluation of the Produced inhibitors identified, several substituent types that significantly increase target affinity, thereby reducing the need for an electrophilic "warhead" functionality. Pronounced PREP specificity within the group Of Clan SC proteases was generally observed. Omission of the P1 electrophilic function did not affect the overall binding mode of three representative compounds, as studied by X-ray crystallography, while the P2 substituents were demonstrated to be accommodated in a cavity of PREP that, to date, has not been probed by inhibitors. Finally, we report on results of selected inhibitors in a SH-SY5Y cellular model of synucleinopathy and demonstrate a significant antiaggregation effect on alpha-synuclein.

  DOI：

  10.1021/jm301060g
• 作为产物：
  描述：

  四氢吡咯 、 (2S,4R)-4-azido-1-(tert-butoxycarbonyl)pyrrolidine-2-carboxylic acid 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 以86%的产率得到(2S,4R)-tert-butyl 4-azido-2-(pyrrolidine-1-carbonyl)pyrrolidine-1-carboxylate
  参考文献：
  名称：

  P2-Substituted N-Acylprolylpyrrolidine Inhibitors of Prolyl Oligopeptidase: Biochemical Evaluation, Binding Mode Determination, and Assessment in a Cellular Model of Synucleinopathy

  摘要：

  We have investigated the effect of regiospecifically , introducing substituents in the P2 part of the typical dipeptide derived basic structure of PREP inhibitors. This hitherto unexplored modification type can be used to improve target affinity, selectivity, and physicochemical parameters in drug discovery programs focusing on PREP inhibitors. Biochemical evaluation of the Produced inhibitors identified, several substituent types that significantly increase target affinity, thereby reducing the need for an electrophilic "warhead" functionality. Pronounced PREP specificity within the group Of Clan SC proteases was generally observed. Omission of the P1 electrophilic function did not affect the overall binding mode of three representative compounds, as studied by X-ray crystallography, while the P2 substituents were demonstrated to be accommodated in a cavity of PREP that, to date, has not been probed by inhibitors. Finally, we report on results of selected inhibitors in a SH-SY5Y cellular model of synucleinopathy and demonstrate a significant antiaggregation effect on alpha-synuclein.

  DOI：

  10.1021/jm301060g

文献信息

• P2-Substituted <i>N</i>-Acylprolylpyrrolidine Inhibitors of Prolyl Oligopeptidase: Biochemical Evaluation, Binding Mode Determination, and Assessment in a Cellular Model of Synucleinopathy
  作者：Pieter Van der Veken、Vilmos Fülöp、Dean Rea、Melanie Gerard、Roos Van Elzen、Jurgen Joossens、Jonathan D. Cheng、Veerle Baekelandt、Ingrid De Meester、Anne-Marie Lambeir、Koen Augustyns

  DOI：10.1021/jm301060g

  日期：2012.11.26

  We have investigated the effect of regiospecifically , introducing substituents in the P2 part of the typical dipeptide derived basic structure of PREP inhibitors. This hitherto unexplored modification type can be used to improve target affinity, selectivity, and physicochemical parameters in drug discovery programs focusing on PREP inhibitors. Biochemical evaluation of the Produced inhibitors identified, several substituent types that significantly increase target affinity, thereby reducing the need for an electrophilic "warhead" functionality. Pronounced PREP specificity within the group Of Clan SC proteases was generally observed. Omission of the P1 electrophilic function did not affect the overall binding mode of three representative compounds, as studied by X-ray crystallography, while the P2 substituents were demonstrated to be accommodated in a cavity of PREP that, to date, has not been probed by inhibitors. Finally, we report on results of selected inhibitors in a SH-SY5Y cellular model of synucleinopathy and demonstrate a significant antiaggregation effect on alpha-synuclein.