N-5-羧基戊基-1-脱氧野尻霉素 | 79206-51-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 中文名称: N-5-羧基戊基-1-脱氧野尻霉素
• 英文名称: N-(5-carboxypentyl)deoxynojirimycin
• 英文别名: N-carboxypentyl-1-deoxynojirimycin；N-(5-carboxypentyl)-1-deoxynojirimycin；5-N-carboxypentyl deoxynojirimycin；N-5-Carboxypentyl-1-deoxynojirimycin；6-[(2R,3R,4R,5S)-3,4,5-trihydroxy-2-(hydroxymethyl)piperidin-1-yl]hexanoic acid
• CAS: 79206-51-2
• 化学式: C₁₂H₂₃NO₆
• 分子量: 277.318
• InChiKey: KTNVTDIFZTZBJY-RBLKWDMZSA-N

物化性质

• 熔点：
  185-187°C
• 沸点：
  534.3±50.0 °C(Predicted)
• 密度：
  1.350±0.06 g/cm3(Predicted)
• 溶解度：
  甲醇（微溶）、水（微溶）

计算性质

• 辛醇/水分配系数(LogP)：
  -3.6
• 重原子数：
  19
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  122
• 氢给体数：
  5
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-5-羧基戊基-1-脱氧野尻霉素 、 N-(6-氨基己基)-5-二甲基氨基萘-1-磺酰胺 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.17h， 以120 mg的产率得到N-(dansylamino)hexylaminocarbonylpentyl-1,5-dideoxy-1,5-imino-D-glucitol
  参考文献：
  名称：

  1-Deoxynojirimycins with dansyl capped N-substituents as probes for Morbus Gaucher affected cell lines

  摘要：

  Cyclization by double reductive amination of D-xylo-hexos-5-ulose with methyl 6-aminohexanoate gave (methoxycarbonyl)pentyl-1-deoxynojirimycin. Reaction of the terminal carboxylic acid with N-dansyl-1,6-diaminohexane provided the corresponding chain-extended fluorescent derivative. By reaction with bis(6-dansylaminohexyl)amine, the corresponding branched di-N-dansyl compound was obtained. Both compounds are strong inhibitors of D-glucosidases and could also be shown to distinctly improve, at sub-inhibitory concentrations, the activity of beta-glucocerebrosidase in a Gaucher fibroblast (N370S) cell-line through chaperoning of the enzyme to the lysosome. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.carres.2010.04.015
• 作为产物：
  描述：

  1-脱氧野尻霉素 在 palladium 10% on activated carbon 、 氢气 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 21.0h， 生成 N-5-羧基戊基-1-脱氧野尻霉素
  参考文献：
  名称：

  合成的1-Deoxynojirimycin N取代肽为N-连接的糖加工提供了更长的中断时间

  摘要：

  合成了一组1-脱氧野oji霉素（DNJ）N-连接的肽。他们在体外针对α-葡萄糖苷酶I和II的IC 50值进行了测量，发现两种同工酶的IC 50值都在微摩尔范围内，并且优于针对α-葡萄糖苷酶II的亚氨基糖N B-DNJ（miglustat，3）。基于细胞的研究表明，尽管游离亚氨基糖3在短期孵育（一天）中能最有效地破坏N-连接的聚糖加工，但是当基于细胞的研究延长至三天时，DNJ N-连接的四肽KDEL ，这是一个内质网（ER）保留序列，表现远好于3。在低抑制剂洗脱研究中，NB-DNJ抑制作用在24小时后降至零，但DNJ-KDEL保留了13％的活性。这种方法为将药物靶向ER并延长其活性提供了一种通用方法。此外，它是模块化的，因此，当发现新的效力增强的亚氨基糖时，可以将它们添加到此模板中进行靶向。

  DOI：

  10.1002/cmdc.201402186

文献信息

• Glycomimetic affinity-enrichment proteomics identifies partners for a clinically-utilized iminosugar
  作者：Isa N. Cruz、Conor S. Barry、Holger B. Kramer、C. Celeste Chuang、Sarah Lloyd、Aarnoud C. van der Spoel、Frances M. Platt、Min Yang、Benjamin G. Davis

  DOI：10.1039/c3sc50826a

  日期：——

  Widescale evaluation of interacting partners for carbohydrates is an underexploited area. Probing of the ‘glyco-interactome’ has particular relevance given the lack of direct genetic control of glycoconjugate biosynthesis. Here we design, create and utilize a natural product-derived glycomimetic iminosugar probe in a Glycomimetic Affinity-enrichment Proteomics (Glyco-AeP) strategy to elucidate key interactions directly from mammalian tissue. The binding partners discovered here and the associated genomic analysis implicate a subset of chaperone and junctional proteins as important in male fertility. Such repurposing of existing therapeutics thus creates direct routes to probing in vivo function. The success of this strategy suggests a general approach to discovering ‘carbohydrate-active’ partners in biology.

  对碳水化合物的相互作用伙伴进行大规模评估是一个尚未充分开发的领域。由于缺乏对糖类共轭物生物合成的直接基因控制，对 "糖类相互作用组 "的探究就显得尤为重要。在这里，我们设计、创建并利用源自天然产物的拟糖亚胺糖探针，采用拟糖亲和力富集蛋白质组学（Glyco-AeP）策略，直接从哺乳动物组织中阐明关键的相互作用。这里发现的结合伙伴和相关的基因组分析表明，伴侣蛋白和连接蛋白是男性生育力的重要因素。因此，这种对现有疗法的重新利用为探测体内功能开辟了直接途径。这一策略的成功为发现生物学中的 "碳水化合物活性 "伙伴提供了一种通用方法。
• Synthesis and biological evaluation of novel biotin–iminoalditol conjugates
  作者：Gerit Pototschnig、Christian Morales De Csáky、Jose R. Montenegro Burke、Georg Schitter、Arnold E. Stütz、Chris A. Tarling、Stephen G. Withers、Tanja M. Wrodnigg

  DOI：10.1016/j.bmcl.2010.05.084

  日期：2010.7

  Biotin-iminosugar conjugates of different configuration such as D-gluco, D-galacto, L-ido as well as a furanoid representative in the D-manno configuration have been synthesised and exhibit powerful inhibition of beta-glucosidase from Agrobacterium sp. with K(i) values in the range of the respective parent compounds. Such molecular probes have potential for activity-based protein pro. ling taking advantage of the biotin-(strept)avidin interaction. (C) 2010 Elsevier Ltd. All rights reserved.
• A METHOD FOR THE TREATMENT OF POMPE DISEASE USING 1-DEOXYNOJIRIMYCIN AND DERIVATIVES
  申请人：Amicus Therapeutics, Inc.

  公开号：EP1896083B1

  公开（公告）日：2016-03-02
• METHOD FOR THE TREATMENT OF POMPE DISEASE USING 1-DEOXYNOJIRIMYCIN DERIVATIVES
  申请人：AMICUS THERAPEUTICS, INC.

  公开号：US20180221357A1

  公开（公告）日：2018-08-09

  The present invention provides a method for increasing the activity of a mutant or wild-type α-glucosidase enzyme in vitro and in vivo by contacting the enzyme with a specific pharmacological chaperone which is a derivative of 1-deoxynojirimycin. The invention also provides a method for the treatment of Pompe disease by administration of chaperone small molecule compound which is a derivative of 1-deoxynojirimycin. The 1-deoxynojirimycin derivative is substituted at the N or C1 position. Combination therapy with replacement α-glucosidase gene or enzyme is also provided.
• US9181184B2
  申请人：——

  公开号：US9181184B2

  公开（公告）日：2015-11-10