[1,3]oxazolo[4,5-b]pyridin-2-yl-[(2S)-pyrrolidin-2-yl]methanol | 1048642-44-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶唑并吡啶类
• 英文名称: [1,3]oxazolo[4,5-b]pyridin-2-yl-[(2S)-pyrrolidin-2-yl]methanol
• CAS: 1048642-44-9
• 化学式: C₁₁H₁₃N₃O₂
• 分子量: 219.243
• InChiKey: ZAKSXLRFPIBWIW-JAVCKPHESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  71.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [1,3]oxazolo[4,5-b]pyridin-2-yl-[(2S)-pyrrolidin-2-yl]methanol 在 草酰氯 、 1-羟基苯并三唑 、 二甲基亚砜 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 作用下， 反应 0.5h， 生成 2-<<1-<<1-(4-phenylbutanoyl)-2(S)-pyrrolidinyl>carbonyl>-2(S)-pyrrolidinyl>carbonyl>oxazolo<4,5-b>pyridine
  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
• 作为产物：
  描述：

  N-allyloxycarbonyl-L-prolinal 在 四(三苯基膦)钯 、 5,5-二甲基-1,3-环己二酮 、 三乙胺 、 乙酰氯 作用下， 以 乙醇 、 二氯甲烷 、 氯仿 、 乙酸乙酯 为溶剂， 反应 30.0h， 生成 [1,3]oxazolo[4,5-b]pyridin-2-yl-[(2S)-pyrrolidin-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.