N-((3S,4R,5S)-4-hydroxy-5-(hydroxymethyl)pyrrolidin-3-yl)acetamide

• 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: N-((3S,4R,5S)-4-hydroxy-5-(hydroxymethyl)pyrrolidin-3-yl)acetamide
• 英文别名: 2-acetamido-1,4-imino-1,2,4-trideoxy-L-arabinitol；N-[(3S,4R,5S)-4-hydroxy-5-(hydroxymethyl)pyrrolidin-3-yl]acetamide
• 化学式: C₇H₁₄N₂O₃
• 分子量: 174.2
• InChiKey: CIBNSHFFZNRICG-LYFYHCNISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.7
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  81.6
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-((3S,4R,5S)-4-hydroxy-5-(hydroxymethyl)pyrrolidin-3-yl)acetamide 、 正戊醛 在 sodium cyanoborohydride 作用下， 以 甲醇 为溶剂， 反应 18.0h， 以63%的产率得到N-((3S,4R,5S)-1-butyl-4-hydroxy-5-(hydroxymethyl)pyrrolidin-3-yl)acetamide
  参考文献：
  名称：

  [EN] GLYCOSIDASE INHIBITORS AND USES THEREOF
  [FR] INHIBITEURS DE GLYCOSIDASES ET LEURS UTILISATIONS

  摘要：

  该发明提供了用于抑制糖苷酶的化合物，这些化合物的前药，以及包括这些化合物或这些化合物的前药的药物组合物。该发明还提供了治疗与O-GlcNAcase的缺乏或过度表达、O-GlcNAc的积累或缺乏相关的疾病和紊乱的方法。

  公开号：

  WO2014032185A1
• 作为产物：
  描述：

  3,5-O-(S)-benzylidene-D-lyxono-1,4-lactone 在 palladium on activated charcoal 、 钯 吡啶 、 锂硼氢 、 sodium azide 、 氢气 、 sodium methylate 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 N-((3S,4R,5S)-4-hydroxy-5-(hydroxymethyl)pyrrolidin-3-yl)acetamide
  参考文献：
  名称：

  Efficient synthesis from d-lyxonolactone of 2-acetamido-1,4-imino-1,2,4-trideoxy-l-arabinitol LABNAc, a potent pyrrolidine inhibitor of hexosaminidases

  摘要：

  The synthesis from D-lyxonolactone of 2-acetamido-1,4-imino-1,2,4-trideOXY-L-arabinitoI LABNAc proceeded in an overall yield of 25%; the enantiomer, 2-acetamido-1,4-imino-1,2,4-trideoxy-D-arabinitol DABNAc, was prepared from L-lyxonolactone. LABNAc and N-benzyl LABNAc are potent non-competitive inhibitors Of D-hexosaminidase, whereas N-benzyl DABNAc exhibits weak competitive inhibition of the enzyme; this provides further evidence in support of Asano's hypothesis that while Dimino sugar mimics inhibit D-glycohydrolases competitively, their L-enantiomers show non-competitive inhibition and in the case of iminofuranoses L-enantiomers are usually more potent inhibitors. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2007.04.041

文献信息

• GLYCOSIDASE INHIBITORS AND USES THEREOF
  申请人：Alectos Therapeutics Inc.

  公开号：US20150218147A1

  公开（公告）日：2015-08-06

  The invention provides compounds for inhibiting glycosidases, prodrugs of the compounds, and pharmaceutical compositions including the compounds or prodrugs of the compounds. The invention also provides methods of treating diseases and disorders related to deficiency or overexpression of O-GlcNAcase, accumulation or deficiency of O-GlcNAc.

  这项发明提供了用于抑制糖苷酶的化合物，这些化合物的前药，以及包括这些化合物或化合物的前药的药物组合物。此外，该发明还提供了治疗与O-GlcNAcase缺乏或过度表达、O-GlcNAc积累或缺乏相关的疾病和障碍的方法。
• METHOD FOR TREATING ALZHEIMER'S DISEASE USING PHARMACOLOGICAL CHAPERONES TO INCREASE THE ACTIVITY OF GANGLIOSIDASES
  申请人：Amicus Therapeutics, Inc.

  公开号：EP2957295B1

  公开（公告）日：2017-08-02
• US9670195B2
  申请人：——

  公开号：US9670195B2

  公开（公告）日：2017-06-06
• Efficient synthesis from d-lyxonolactone of 2-acetamido-1,4-imino-1,2,4-trideoxy-l-arabinitol LABNAc, a potent pyrrolidine inhibitor of hexosaminidases
  作者：J.S.Shane Rountree、Terry D. Butters、Mark R. Wormald、Raymond A. Dwek、Naoki Asano、Kyoko Ikeda、Emma L. Evinson、Robert J. Nash、George W.J. Fleet

  DOI：10.1016/j.tetlet.2007.04.041

  日期：2007.6

  The synthesis from D-lyxonolactone of 2-acetamido-1,4-imino-1,2,4-trideOXY-L-arabinitoI LABNAc proceeded in an overall yield of 25%; the enantiomer, 2-acetamido-1,4-imino-1,2,4-trideoxy-D-arabinitol DABNAc, was prepared from L-lyxonolactone. LABNAc and N-benzyl LABNAc are potent non-competitive inhibitors Of D-hexosaminidase, whereas N-benzyl DABNAc exhibits weak competitive inhibition of the enzyme; this provides further evidence in support of Asano's hypothesis that while Dimino sugar mimics inhibit D-glycohydrolases competitively, their L-enantiomers show non-competitive inhibition and in the case of iminofuranoses L-enantiomers are usually more potent inhibitors. (c) 2007 Elsevier Ltd. All rights reserved.
• [EN] GLYCOSIDASE INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DE GLYCOSIDASES ET LEURS UTILISATIONS
  申请人：ALECTOS THERAPEUTICS INC

  公开号：WO2014032185A1

  公开（公告）日：2014-03-06

  The invention provides compounds for inhibiting glycosidases, prodrugs of the compounds, and pharmaceutical compositions including the compounds or prodrugs of the compounds. The invention also provides methods of treating diseases and disorders related to deficiency or overexpression of O-GlcNAcase, accumulation or deficiency of O-GlcNAc.

  该发明提供了用于抑制糖苷酶的化合物，这些化合物的前药，以及包括这些化合物或这些化合物的前药的药物组合物。该发明还提供了治疗与O-GlcNAcase的缺乏或过度表达、O-GlcNAc的积累或缺乏相关的疾病和紊乱的方法。