(5R,6R,7S,8S)-5-(hydroxymethyl)-2-octyl-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-6,7,8-triol | 851445-82-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并吡啶类
• 英文名称: (5R,6R,7S,8S)-5-(hydroxymethyl)-2-octyl-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-6,7,8-triol
• 英文别名: (5R,6R,7S,8S)-5-hydroxymethyl-2-n-octyl-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-6,7,8-triol
• CAS: 851445-82-4
• 化学式: C₁₆H₂₈N₂O₄
• 分子量: 312.409
• InChiKey: OMVDIWMZQBJVFN-APIJFGDWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  98.7
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (5R,6R,7S,8S)-6,7,8-tris(benzyloxy)-5-[(benzyloxy)-methyl]-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine 在 N-碘代丁二酰亚胺 、 copper(l) iodide 、 四(三苯基膦)钯 、 palladium on carbon 、 乙基溴化镁 、 氢气 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 80.0 ℃ 、600.01 kPa 条件下， 反应 65.17h， 生成 (5R,6R,7S,8S)-5-(hydroxymethyl)-2-octyl-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-6,7,8-triol
  参考文献：
  名称：

  Structure–activity relationships in a series of C2-substituted gluco-configured tetrahydroimidazopyridines as β-glucosidase inhibitors

  摘要：

  Inhibition of glycoside hydrolases has widespread application in treatment of diabetes, viral infections, lysosomal storage diseases and cancers. Gluco-configured tetrahydroimidazopyridines are the most potent beta-glucosidase inhibitors reported to date. Using transition state mimic strategy, a series of C2-substituted gluco-configured tetrahydroimidazopyridines were designed and synthesized. Compounds 3 (K-i = 0.64 nM) and 5 (K-i = 0.58 nM) showed stronger inhibitory potency against beta-glucosidase. Maestro 9.1 was used to study the structure-activity relationships by docking the compounds into the beta-glucosidase active sites. Crown Copyright (C) 2011 Published by Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.02.043

文献信息

• Glucoimidazole and polyhydroxycyclohexenyl amine derivatives to treat gaucher disease
  申请人：Fan Jian-Qiang

  公开号：US20050137223A1

  公开（公告）日：2005-06-23

  The present invention provides glucoimidazole (GIZ) and polyhydroxycyclohexenyl amine (PHCA) derivatives, methods of making them, and methods of use where the GIZ and PHCA derivatives have a short, flexible linker emanating from the corresponding position of the ring oxygen in a pyranose; and a lipophilic moiety connected to the linker and pharmaceutically acceptable salts thereof. More particularly, the present invention further provides a method for treating individuals having Gaucher disease by administering the novel GIZ or PHCA derivatives as “active-site specific chaperones” for the mutant glucocerebrosidase associated with the disease.

  本发明提供了葡萄糖咪唑（GIZ）和多羟基环己烯基胺（PHCA）衍生物，其制备方法以及使用方法。其中，GIZ和PHCA衍生物具有从吡喃糖环氧原子相应位置发出的短、柔性连接器；以及连接到连接器的亲脂性基团和其药学上可接受的盐。更具体地，本发明还提供了一种治疗高氏病患者的方法，即通过将新型GIZ或PHCA衍生物作为“活性位点特异性伴侣蛋白”，用于治疗与该疾病相关的突变型葡萄糖鞘脂酶。
• METHOD FOR THE TREATMENT OF NEUROLOGICAL DISORDERS BY ENHANCING THE ACTIVITY OF BETA-GLUCOCEREBROSIDASE
  申请人：Wustman Alan Brandon

  公开号：US20080009516A1

  公开（公告）日：2008-01-10

  Provided is a method of increasing the stability of wild-type β-glucocerebrosidase. Also provided are methods of treating and/or preventing an individual having a neurological disease in which increased expression or activity of β-glucocerebrosidase in the central nervous system would be beneficial. This method comprises administering an effective amount of a pharmacologic chaperone for β-glucocerebrosidase, with the proviso that the individual does not have a mutation in the gene encoding β-glucocerebrosidase. Further provided are β-glucocerebrosidase inhibitors which have been identified as specific pharmacologic chaperones and which have been shown to increase activity of β-glucocerebrosidase in vivo in the central nervous system.

  提供了一种增加野生型β-葡萄糖苷酶稳定性的方法。同时，提供了一种治疗和/或预防神经系统疾病的方法，其中在中枢神经系统中增加β-葡萄糖苷酶的表达或活性将有益。该方法包括给予β-葡萄糖苷酶的药理伴侣的有效剂量，但前提是该个体没有β-葡萄糖苷酶编码基因的突变。进一步提供了β-葡萄糖苷酶抑制剂，这些抑制剂已被确定为特定的药理伴侣，并已被证明在中枢神经系统内增加β-葡萄糖苷酶的活性。
• Method for the treatment of neurological disorders by enhancing the activity of β-glucocerebrosidase
  申请人：Amicus Therapeutics, Inc.

  公开号：US07829579B2

  公开（公告）日：2010-11-09

  Provided is a method of increasing the stability of wild-type β-glucocerebrosidase. Also provided are methods of treating and/or preventing an individual having a neurological disease in which increased expression or activity of β-glucocerebrosidase in the central nervous system would be beneficial. This method includes administering an effective amount of a pharmacologic chaperone for β-glucocerebrosidase, with the proviso that the individual does not have a mutation in the gene encoding β-glucocerebrosidase. Further provided are β-glucocerebrosidase inhibitors which have been identified as specific pharmacologic chaperones and which have been shown to increase activity of β-glucocerebrosidase in vivo in the central nervous system.

  提供了一种增加野生型β-葡萄糖苷酶稳定性的方法。还提供了一种治疗和/或预防神经系统疾病的方法，其中在中枢神经系统中增加β-葡萄糖苷酶的表达或活性将是有益的。该方法包括在有效剂量下给予β-葡萄糖苷酶的药理伴侣，但前提是个体没有β-葡萄糖苷酶编码基因的突变。此外，还提供了已被确定为特定药理伴侣的β-葡萄糖苷酶抑制剂，已经证明它们可以在中枢神经系统中增加β-葡萄糖苷酶的活性。
• Method for the Treatment of Neurological Disorders by Enhancing the Activity of Beta-Glucocerebrosidase
  申请人：Amicus Therapeutics, Inc.

  公开号：US20150025109A1

  公开（公告）日：2015-01-22

  Provided is a method of increasing the stability of wild-type β-glucocerebrosidase. Also provided are methods of treating and/or preventing an individual having a neurological disease in which increased expression or activity of β-glucocerebrosidase in the central nervous system would be beneficial. This method comprises administering an effective amount of a pharmacologic chaperone for β-glucocerebrosidase, with the proviso that the individual does not have a mutation in the gene encoding β-glucocerebrosidase. Further provided are β-glucocerebrosidase inhibitors which have been identified as specific pharmacologic chaperones and which have been shown to increase activity of β-glucocerebrosidase in vivo in the central nervous system.

  提供了一种增加野生型β-葡萄糖苷酶稳定性的方法。还提供了治疗和/或预防神经系统疾病的方法，其中在中枢神经系统中增加β-葡萄糖苷酶的表达或活性将有益。该方法包括给予β-葡萄糖苷酶药理伴侣的有效剂量，前提是个体没有β-葡萄糖苷酶编码基因的突变。此外，还提供了已被确定为特定药理伴侣并已被证明能够在中枢神经系统中增加β-葡萄糖苷酶活性的β-葡萄糖苷酶抑制剂。
• Method for the treatment of neurological disorders by enhancing the activity of beta-glucocerebrosidase
  申请人：Wustman Brandon Alan

  公开号：US09119845B2

  公开（公告）日：2015-09-01

  Provided is a method of increasing the stability of wild-type β-glucocerebrosidase. Also provided are methods of treating and/or preventing an individual having a neurological disease in which increased expression or activity of β-glucocerebrosidase in the central nervous system would be beneficial. This method includes administering an effective amount of a pharmacologic chaperone for β-glucocerebrosidase, with the proviso that the individual does not have a mutation in the gene encoding β-glucocerebrosidase. Further provided are β-glucocerebrosidase inhibitors which have been identified as specific pharmacologic chaperones and which have been shown to increase activity of β-glucocerebrosidase in vivo in the central nervous system.

  提供了一种增加野生型β-葡萄糖苷酶稳定性的方法。还提供了一种治疗和/或预防神经系统疾病的方法，其中在中枢神经系统中增加β-葡萄糖苷酶的表达或活性将有益。该方法包括给予β-葡萄糖苷酶的药理伴侣的有效量，前提是该个体没有β-葡萄糖苷酶编码基因的突变。此外，还提供了已被确定为特异性药理伴侣并已在中枢神经系统内显示增加β-葡萄糖苷酶活性的β-葡萄糖苷酶抑制剂。