N-hexyl-1-deoxynojirimycin | 81117-34-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: N-hexyl-1-deoxynojirimycin
• 英文别名: (2R,3R,4R,5S)-1-hexyl-2-(hydroxymethyl)piperidine-3,4,5-triol；N-hexyl-DNJ；1,5-(hexylimino)-1,5-dideoxy-D-glucitol；N-(n-hexyl)-1,5-dideoxy-1,5-imino-D-glucitol
• CAS: 81117-34-2
• 化学式: C₁₂H₂₅NO₄
• 分子量: 247.335
• InChiKey: KRNOSIJCJVCXKU-WRWGMCAJSA-N

物化性质

• 沸点：
  416.8±45.0 °C(Predicted)
• 密度：
  1.174±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  84.2
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (2R,3R,4R,5S)-3,4,5-三(苄氧基)-2-[(苄氧基)甲基]哌啶 在 盐酸 、 palladium on carbon 、 氢气 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 70.0 ℃ 、400.01 kPa 条件下， 反应 24.0h， 生成 N-hexyl-1-deoxynojirimycin
  参考文献：
  名称：

  基于荧光偏振活性的蛋白质谱分析法在人类非溶酶体葡萄糖基神经酰胺酶的有效，选择性抑制剂的发现中。

  摘要：

  人非溶酶体葡萄糖基神经酰胺酶（GBA2）是控制糖脂水平的几种酶之一，其活性与几种人类疾病状态相关。迫切需要设计或发现选择性的GBA2抑制剂作为化学工具和潜在的治疗剂。在这里，我们描述了基于荧光偏振活性的蛋白质谱分析（FluoPol-ABPP）测定法的发展，该测定法可从350多种亚氨基糖文库中快速鉴定GBA2抑制剂。基于FluoPol-ABPP筛选的线索生成聚焦库，并针对与其他葡糖神经酰胺代谢酶，葡糖神经酰胺合酶（GCS），溶酶体葡糖神经酰胺酶（GBA）和胞质保留β-葡糖苷酶GBA3的GBA2选择性偏移进行评估。我们的工作产生了有效的和选择性的GBA2抑制剂，

  DOI：

  10.1021/jacs.7b07352

文献信息

• 1,5-dideoxy-1,5-imino-D-glucitol derivatives
  申请人：G. D. Searle & Co.

  公开号：US05221746A1

  公开（公告）日：1993-06-22

  O-acylated derivatives of 1,5-dideoxy-1,5-imino-D-glucitol are disclosed that contain an N-alkyl or N-aroyl radical in which from one to four of the free hydroxyl groups are O-acylated with carboxylic alkanoyl radicals selected from the group consisting of .omega.,.omega.,.omega.-trifluoro alkanoyl having from three to eight carbon atoms, carboxylic cycloalkanoyl groups having from four to eight carbon atoms and carboxylic acyclic alkanoyl groups having from two to ten carbon atoms, wherein the N-aroyl radical is selected from the group consisting of p-decylbenzoyl, 3-(p-chlorophenoxy)propanoyl, 2-(acetyloxy)benzoyl, [1,1'-biphenyl]-4-ylcarbonyl, 2-thiopheneacetyl, trans-3-furanacryloyl 3-methoxyphenylacetyl and 3-(trifluoromethyl)benzoyl, and wherein the N-alkyl contains from one to fourteen carbon atoms, provided that when N-alkyl contains from one to five carbon atoms the O-acylated groups are .omega.,.omega.,.omega.-trifluoro alkanoyl or carboxylic cycloalkanoyl.

  披露了1,5-二去氧-1,5-亚胺-D-葡萄糖醇的O-酰化衍生物，其中含有一个到四个自由羟基被选自以下羧基烷酰基的羧基烷酰基的N-烷基或N-芳酰基，.omega.，.omega.，.omega.-三氟烷酰基，碳原子数为三至八个，具有四至八个碳原子的羧基环烷酰基和具有两至十个碳原子的羧基无环烷酰基，其中N-芳酰基选自以下羧基苯基，3-(对氯苯氧基)丙酰基，2-(乙酰氧基)苯甲酰基，[1,1'-联苯]-4-基甲酰基，2-噻吩乙酰基，反式-3-呋喃丙烯基3-甲氧基苯乙酰基和3-(三氟甲基)苯甲酰基，其中N-烷基含有一个到十四个碳原子，前提是当N-烷基含有一个到五个碳原子时，O-酰化基团为.omega.，.omega.，.omega.-三氟烷酰基或羧基环烷酰基。
• Antiviral compounds
  申请人：G. D. Searle & Co.

  公开号：US05310745A1

  公开（公告）日：1994-05-10

  A method of inhibiting lentivirus is disclosed which comprises mammalian host susceptible to said lentivirus with a virally inhibitory effective amount of an O-acylated derivative of 1,5-dideoxy-1,5-imino-D-glucitol and their N-alkyl, N-acyl and N-aroyl derivatives in which from one to four of the free hydroxyl groups are O-acylated with carboxylic alkanoyl radicals selected from the group consisting of .omega.,.omega.,.omega.-trifluoroalkanoyl having from three to eight carbon atoms, carboxylic cycloalkanoyl groups having from four to eight carbon atoms and carboxylic acyclic alkanoyl groups having from two to ten carbon atoms, wherein the N-aroyl groups contain from 7 to 14 carbon atoms, the N-acyl groups contain from 4 to 8 carbon atoms and the N-alkyl groups contain from 1 to 14 carbon atoms.

  本发明揭示了一种抑制慢病毒的方法，包括将哺乳动物宿主暴露于所述慢病毒的有效抑制量的1,5-二去氧-1,5-亚胺-D-葡萄糖醇的O-酰化衍生物及其N-烷基，N-酰基和N-芳酰衍生物中，其中从一个到四个自由羟基被选自由三至八个碳原子的羧基烷酰基的.omega.，.omega.，.omega.-三氟烷酰基，含有四至八个碳原子的环烷基羧基和含有两至十个碳原子的无环烷基羧基，其中N-芳酰基含有七至十四个碳原子，N-酰基含有四至八个碳原子，N-烷基含有一至十四个碳原子。
• Identification of Potent and Selective Glucosylceramide Synthase Inhibitors from a Library of N-Alkylated Iminosugars
  作者：Amar Ghisaidoobe、Pieter Bikker、Arjan C. J. de Bruijn、Frithjof D. Godschalk、Eva Rogaar、Marieke C. Guijt、Peter Hagens、Jerre M. Halma、Steven M. van't Hart、Stijn B. Luitjens、Vincent H. S. van Rixel、Mark Wijzenbroek、Thor Zweegers、Wilma E. Donker-Koopman、Anneke Strijland、Rolf Boot、Gijs van der Marel、Herman S. Overkleeft、Johannes M. F. G. Aerts、Richard J. B. H. N. van den Berg

  DOI：10.1021/ml100192b

  日期：2011.2.10

  iminosugar type GCS inhibitors often also inhibit to some extent human acid glucosylceramidase (GBA1) and the nonlysosomal glucosylceramidase (GBA2), the two enzymes known to process glucosylceramide. Of these, GBA1 itself is a potential drug target for the treatment of the lysosomal storage disorder, Gaucher disease, and selective GBA1 inhibitors are sought after as potential chemical chaperones. The physiological

  葡萄糖基神经酰胺合酶（GCS）是用于临床治疗溶酶体贮积症的重要药物，也是抗击2型糖尿病的有希望的药物。氨基糖是开发GCS抑制剂的有用线索。然而，据报道，有效的亚氨基糖型GCS抑制剂与其他糖加工酶具有不必要的交叉反应性。特别是，亚氨基糖型GCS抑制剂通常还会在一定程度上抑制人酸性葡糖神经酰胺酶（GBA1）和非溶酶体葡糖神经酰胺酶（GBA2），这两种酶均已知可处理葡糖神经酰胺。其中，GBA1本身是用于治疗溶酶体贮积病，高雪氏病的潜在药物靶标，并且选择性的GBA1抑制剂被寻求作为潜在的化学伴侣。关于疾病状态，GBA2在糖基神经酰胺加工中的生理重要性尚不十分清楚，在此，选择性抑制剂可以用作化学敲除实体。在本次交流中，我们报告了对高度有效和选择性的N-烷基化L-氨基构型亚氨基糖的鉴定。特别是，GCS对GBA1的选择性为27。
• 1,5-dideoxy-1,5-imino-d-glucitol derivatives
  申请人：G. D. Searle & Co.

  公开号：US05144037A1

  公开（公告）日：1992-09-01

  Antiviral O-acylated derivatives of 1,5-dideoxy-1,5-imino-D-glucitol are disclosed that contain an N-alkyl or N-aroyl radical in which from one to four of the free hydroxyl groups are O-acylated with carboxylic alkanoyl radicals selected from the group consisting of .omega.,.omega.,.omega.-trifluoro alkanoyl having from three to eight carbon atoms, carboxylic cycloalkanoyl groups having from four to eight carbon atoms and carboxylic acyclic alkanoyl groups having from two to ten carbon atoms, wherein the N-aroyl radical is selected from the group consisting of p-decylbenzoyl, 3-(p-chlorophenoxy)propanoyl, 2-(acetyloxy)benzoyl, [1,1'-biphenyl]-4-ylcarbonyl, 2-thiopheneacetyl, trans-3-furanacryloyl, 3-methoxyphenylacetyl and 3-(trifluoromethyl)benzoyl, and wherein the N-alkyl contains from one to fourteen carbon atoms, provided that when N-alkyl contains from one to five carbon atoms the O-acylated groups are .omega.,.omega.,.omega.-trifluoro alkanoyl or carboxylic cycloalkanoyl.

  本发明涉及1,5-二去氧-1,5-亚硝基-D-葡萄糖醇的抗病毒O-酰化衍生物，其中含有一个至四个游离羟基被选自由从三到八个碳原子的羧基脂肪酰基所选择的ω,ω,ω-三氟代烷酰基、从四到八个碳原子的环烷基羧基和从二到十个碳原子的非环烷基羧基的N-烷基或N-芳酰基，其中N-芳酰基被选自p-癸基苯甲酰基、3-(对氯苯氧基)丙酰基、2-(乙酰氧基)苯甲酰基、[1,1'-联苯]-4-基羰基、2-噻吩乙酰基、反式-3-呋喃丙烯酰基、3-甲氧基苯乙酰基和3-(三氟甲基)苯甲酰基，其中N-烷基含有从一个到十四个碳原子，但当N-烷基含有从一个到五个碳原子时，O-酰化基为ω,ω,ω-三氟代烷酰基或环烷基羧基。
• α-1-C-Octyl-1-deoxynojirimycin as a pharmacological chaperone for Gaucher disease
  作者：Liang Yu、Kyoko Ikeda、Atsushi Kato、Isao Adachi、Guillaume Godin、Philippe Compain、Olivier Martin、Naoki Asano

  DOI：10.1016/j.bmc.2006.08.003

  日期：2006.12

  beta-Glu activity without affecting the intracellular alpha-Glu activity for 10 days. Only CO-DNJ showed a weak beta-Glu chaperoning activity in the L444P type 2 variant, with 1.2-fold increase at 5-20 microM, and furthermore maximally increased the alpha-Glu activity by 1.3-fold at 20 microM. These experimental results suggest that CO-DNJ is a significant pharmacological chaperone for N370S Gaucher variants

  最常见的溶酶体贮积病是高雪氏病，是由溶酶体β-葡萄糖苷酶（β-Glu，也称为β-葡萄糖脑苷脂酶）的某些变体折叠和运输效率低下引起的。最近，Sawker等。报道称，在高歇患者来源的细胞中添加亚抑制浓度（10 microM）的药理伴侣N-壬基-1-脱氧野oji霉素（NN-DNJ）（10）会导致突变体（N370S）活性增加2倍酶[Proc。Natl。学院 科学 USA2002，99，15428]。然而，我们发现，尽管N370S成纤维细胞具有出色的伴侣活性，但在整个检测期间，添加10 microM的NN-DNJ可使溶酶体α-葡萄糖苷酶（alpha-Glu）活性降低了50％。因此，我们制备了一系列在C-1alpha位置具有烷基链的DNJ衍生物，并评估了它们的体外抑制活性和作为Gaucher细胞系药理伴侣的潜能。其中，α-1-C-辛基-DNJ（CO-DNJ）（15）对DN-Glu的体外抑制活性比DNJ