(2S,3R,4R,5S,6R)-6-(acetoxymethyl)-3-(3-methylthioureido)-tetrahydro-2H-pyran-2,4,5-triyl triacetate | 1009816-88-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (2S,3R,4R,5S,6R)-6-(acetoxymethyl)-3-(3-methylthioureido)-tetrahydro-2H-pyran-2,4,5-triyl triacetate
• 英文别名: [(2R,3S,4R,5R,6S)-3,4,6-triacetyloxy-5-(methylcarbamothioylamino)oxan-2-yl]methyl acetate
• CAS: 1009816-88-9
• 化学式: C₁₆H₂₄N₂O₉S
• 分子量: 420.441
• InChiKey: XJCPUEDUWFOYTL-KJWHEZOQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  28
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  171
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  (2S,3R,4R,5S,6R)-6-(acetoxymethyl)-3-(3-methylthioureido)-tetrahydro-2H-pyran-2,4,5-triyl triacetate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 (3aR,5R,6S,7R,7aR)-(5-(acetoxymethyl)-2-(methylamino)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazole-6,7-diyl)diacetate
  参考文献：
  名称：

  Analysis of transition state mimicry by tight binding aminothiazoline inhibitors provides insight into catalysis by human O-GlcNAcase

  摘要：

  2'-氨基噻唑啉抑制剂是人OGA的紧密结合过渡态模拟物，其结合依赖于抑制剂的pKa。

  DOI：

  10.1039/c6sc00370b
• 作为产物：
  描述：

  1,3,4,6-四-O-乙酰基-2-氨基-2-脱氧-Β-D-葡萄糖盐酸盐 在 三乙胺 作用下， 以 二氯甲烷 、 水 、 乙腈 为溶剂， 生成 (2S,3R,4R,5S,6R)-6-(acetoxymethyl)-3-(3-methylthioureido)-tetrahydro-2H-pyran-2,4,5-triyl triacetate
  参考文献：
  名称：

  Analysis of transition state mimicry by tight binding aminothiazoline inhibitors provides insight into catalysis by human O-GlcNAcase

  摘要：

  2'-氨基噻唑啉抑制剂是人OGA的紧密结合过渡态模拟物，其结合依赖于抑制剂的pKa。

  DOI：

  10.1039/c6sc00370b

文献信息

• SELECTIVE GLYCOSIDASE INHIBITORS AND USES THEREOF
  申请人：Vocadlo David

  公开号：US20100016386A1

  公开（公告）日：2010-01-21

  The invention provides compounds of formula (I) for selectively 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

  该发明提供了式(I)的化合物，用于选择性抑制酶，该化合物的前药以及包括化合物或化合物前药的药物组合物。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。
• Selective glycosidase inhibitors and uses thereof
  申请人：Simon Fraser University

  公开号：US08334310B2

  公开（公告）日：2012-12-18

  The invention provides compounds of formula (I) for selectively 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

  该发明提供了式（I）的化合物，用于选择性抑制糖苷酶，该化合物的前药物以及包括该化合物或其前药物的制药组合物。该发明还提供了治疗与O-GlcNA酶缺乏或过度表达、O-GlcNAc的积累或缺乏有关的疾病和障碍的方法。
• WO2008/25170
  申请人：——

  公开号：——

  公开（公告）日：——
• Exploring NAG‐thiazoline and its derivatives as inhibitors of chitinolytic β‐acetylglucosaminidases
  作者：Tian Liu、Meng Xia、Haitao Zhang、Hao Zhou、Jing Wang、Xu Shen、Qing Yang

  DOI：10.1016/j.febslet.2014.11.032

  日期：2015.1

  NAG‐thiazoline (NGT) and its derivatives are well‐known inhibitors against most β‐acetylglucosaminidases (β‐GlcNAcases) except for insect and bacterial chitinolytic β‐GlcNAcases, including the molting‐indispensable OfHex1 from the insect Ostrinia furnacalis. Here, we report the co‐crystal structure of OfHex1 in complex with NGT. This structure reveals a large active pocket in OfHex1 that may account for the poor inhibitory activity of NGT. To test this hypothesis, a bulky substituent was designed and synthesized on the thiazoline ring of NGT. The resulting compound (NMAGT) was determined to be a submicromolar inhibitor of OfHex1 with a K i value of 0.13 μM, which is 600‐fold lower than K i value of NGT. Molecular dynamics simulation analysis supported the good fit of NMAGT to the active pocket.
• US8334310B2
  申请人：——

  公开号：US8334310B2

  公开（公告）日：2012-12-18