1-<1-(tert-butyloxycarbonyl)-2(S)-pyrrolidinyl>-1-(pyridin-2-yl)methanol | 929911-40-0

• 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-(pyridin-2-yl)methanol
• 英文别名: 2-[(Pyridin-2-yl)hydroxymethyl]-1-N-(tert-butoxycarbonyl)-(2S)-pyrrolidine；tert-butyl (2S)-2-[hydroxy(pyridin-2-yl)methyl]pyrrolidine-1-carboxylate
• CAS: 929911-40-0
• 化学式: C₁₅H₂₂N₂O₃
• 分子量: 278.351
• InChiKey: BYXRLDKFBBCYJQ-UEWDXFNNSA-N

物化性质

• 沸点：
  403.9±20.0 °C(Predicted)
• 密度：
  1.175±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  62.7
• 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-(pyridin-2-yl)methanol 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 pyridin-2-yl-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
• 作为产物：
  描述：

  2-溴吡啶 、 (S)-N-Boc-吡咯烷-2-甲醛 N-(叔丁氧羰基)-L-脯氨醛 在 正丁基锂 作用下， 生成 1-<1-(tert-butyloxycarbonyl)-2(S)-pyrrolidinyl>-1-(pyridin-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

• Peptidyl ketones as inhibitors of DPIV
  申请人：——

  公开号：US20030148961A1

  公开（公告）日：2003-08-07

  The present invention relates to compounds of the general formula 1 1 and pharmaceutically acceptable salts thereof, to the use of the compounds for the treatment of impaired glucose tolerance, glucosuria, hyperlipidaemia, metabolic acidosis, diabetes mellitus, diabetic neuropathy and nephropathy and of sequelae caused by diabetes mellitus in mammals.

  本发明涉及一般式11的化合物及其药学上可接受的盐，以及该化合物用于治疗哺乳动物中的糖耐量受损、糖尿病、高脂血症、代谢性酸中毒、糖尿病神经病和肾病以及由糖尿病引起的后遗症的用途。
• PEPTIDYL KETONES AS INHIBITORS OF DPIV
  申请人：Probiodrug AG

  公开号：EP1434792A2

  公开（公告）日：2004-07-07
• US7608577B2
  申请人：——

  公开号：US7608577B2

  公开（公告）日：2009-10-27
• [EN] PEPTIDYL KETONES AS INHIBITORS OF DPIV<br/>[FR] PEPTIDYL-CETONES COMME INHIBITEURS DE MOLECULES DIPEPTIDYL PEPTIDASE DE TYPE IV
  申请人：PROBIODRUG AG

  公开号：WO2003033524A2

  公开（公告）日：2003-04-24

  The present invention relates to compounds of the general formula (I), and pharmaceutically acceptable salts thereof, to the use of the compounds for the treatment of impaired glucose tolerance, glucosuria, hyperlipidaemia, metabolic acidosis, diabetes mellitus, diabetic neuropathy and nephropathy and of sequelae caused by diabetes mellitus in mammals.
• 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.