1-<1-(tert-butyloxycarbonyl)-2(S)-pyrrolidinyl>-1-(thiophene-2-yl)methanol | 929911-41-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: 1-<1-(tert-butyloxycarbonyl)-2(S)-pyrrolidinyl>-1-(thiophene-2-yl)methanol
• 英文别名: tert-butyl (2S)-2-[hydroxy(thiophen-2-yl)methyl]pyrrolidine-1-carboxylate
• CAS: 929911-41-1
• 化学式: C₁₄H₂₁NO₃S
• 分子量: 283.392
• InChiKey: HSSZBYOKOYXXGD-NUHJPDEHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  78
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-<1-(tert-butyloxycarbonyl)-2(S)-pyrrolidinyl>-1-(thiophene-2-yl)methanol 在 戴斯-马丁氧化剂 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以87%的产率得到(2S)-N-Boc-2-thienylcarbonylpyrrolidine
  参考文献：
  名称：

  2(S)-(Cycloalk-1-enecarbonyl)-1-(4-phenyl-butanoyl)pyrrolidines and 2(S)-(aroyl)-1-(4-phenylbutanoyl)pyrrolidines as prolyl oligopeptidase inhibitors

  摘要：

  In order to replace the P2-P1 amide group, different 1-cycloalkenyls and 2-aryls were studied in the place of the PI pyrrolidine group of a 4-phenylbutanoyl-L-Pro-pyrrolidine structure, which is a well-known prolyl oligopeptidase inhibitor SUAM-1221. The 1-cyclopentenyl and the 2-thienyl groups gave novel compounds, which were equipotent with the corresponding pyrrolidine-analog SUAM-1221. It was shown that the P2-P1 amide group of POP inhibitors can be replaced by an alpha, beta-unsaturated carbonyl group or the aryl conjugated carbonyl group. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.12.036
• 作为产物：
  描述：

  2-噻吩基锂 、 (S)-N-Boc-吡咯烷-2-甲醛 N-(叔丁氧羰基)-L-脯氨醛 以 四氢呋喃 为溶剂， 反应 4.0h， 以76%的产率得到1-<1-(tert-butyloxycarbonyl)-2(S)-pyrrolidinyl>-1-(thiophene-2-yl)methanol
  参考文献：
  名称：

  Synthesis and Structure-Activity Relationships of Peptidyl .alpha.-Keto Heterocycles as Novel Inhibitors of Prolyl Endopeptidase

  摘要：

  The preparation and in vitro prolyl endopeptidase (PEP) inhibitory activity of a series of alpha-keto heterocyclic compounds is described. The design is based on the introduction of alpha-keto heterocycles at the C-terminal end of substrate-like peptides. Many of the compounds including those substituted with thiazole, benzothiazole, benzoxazole, imidazole, and pyridine groups exhibit IC50 potencies of PEP inhibition at nanomolar levels. Structure-activity studies of the C-terminal heterocyclic groups indicate the importance of an sp(2) nitrogen atom at a beta-position from the adjoining ketone carbonyl group. This heterocyclic nitrogen atom would provide a critical hydrogen-bond interaction with the histidine residue of the catalytic triad in PEP. Our inhibitors would extend the generality of the alpha-keto heterocycle design to another serine protease.

  DOI：

  10.1021/jm00047a007

文献信息

• Synthesis and Structure-Activity Relationships of Peptidyl .alpha.-Keto Heterocycles as Novel Inhibitors of Prolyl Endopeptidase
  作者：Seiji Tsutsumi、Tsuneo Okonogi、Seiji Shibahara、Shokichi Ohuchi、Emiko Hatsushiba、Arthur A. Patchett、Burton G. Christensen

  DOI：10.1021/jm00047a007

  日期：1994.10

  The preparation and in vitro prolyl endopeptidase (PEP) inhibitory activity of a series of alpha-keto heterocyclic compounds is described. The design is based on the introduction of alpha-keto heterocycles at the C-terminal end of substrate-like peptides. Many of the compounds including those substituted with thiazole, benzothiazole, benzoxazole, imidazole, and pyridine groups exhibit IC50 potencies of PEP inhibition at nanomolar levels. Structure-activity studies of the C-terminal heterocyclic groups indicate the importance of an sp(2) nitrogen atom at a beta-position from the adjoining ketone carbonyl group. This heterocyclic nitrogen atom would provide a critical hydrogen-bond interaction with the histidine residue of the catalytic triad in PEP. Our inhibitors would extend the generality of the alpha-keto heterocycle design to another serine protease.
• 2(S)-(Cycloalk-1-enecarbonyl)-1-(4-phenyl-butanoyl)pyrrolidines and 2(S)-(aroyl)-1-(4-phenylbutanoyl)pyrrolidines as prolyl oligopeptidase inhibitors
  作者：Elina M. Jarho、Jarkko I. Venäläinen、Sami Poutiainen、Harri Leskinen、Jouko Vepsäläinen、Johannes A.M. Christiaans、Markus M. Forsberg、Pekka T. Männistö、Erik A.A. Wallén

  DOI：10.1016/j.bmc.2006.12.036

  日期：2007.3

  In order to replace the P2-P1 amide group, different 1-cycloalkenyls and 2-aryls were studied in the place of the PI pyrrolidine group of a 4-phenylbutanoyl-L-Pro-pyrrolidine structure, which is a well-known prolyl oligopeptidase inhibitor SUAM-1221. The 1-cyclopentenyl and the 2-thienyl groups gave novel compounds, which were equipotent with the corresponding pyrrolidine-analog SUAM-1221. It was shown that the P2-P1 amide group of POP inhibitors can be replaced by an alpha, beta-unsaturated carbonyl group or the aryl conjugated carbonyl group. (c) 2007 Elsevier Ltd. All rights reserved.