N-[5-(pyren-1-ylmethoxy)pentyl]-1-deoxynojirimycin

• 分子结构分类: 有机化合物 - 苯类化合物 - 芘
• 英文名称: N-[5-(pyren-1-ylmethoxy)pentyl]-1-deoxynojirimycin
• 英文别名: (2R,3R,4R,5S)-2-(hydroxymethyl)-1-[5-(pyren-1-ylmethoxy)pentyl]piperidine-3,4,5-triol
• 化学式: C₂₈H₃₃NO₅
• 分子量: 463.574
• InChiKey: IMYBJLKJUZUZCD-WKWYISCVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  34
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  93.4
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  1-脱氧野尻霉素 、 5-(methylpyrenyl)oxy-1-bromopentane 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以7%的产率得到N-[5-(pyren-1-ylmethoxy)pentyl]-1-deoxynojirimycin
  参考文献：
  名称：

  Identification and Development of Biphenyl Substituted Iminosugars as Improved Dual Glucosylceramide Synthase/Neutral Glucosylceramidase Inhibitors

  摘要：

  This work details the evaluation of a number of N-alkylated deoxynojirimycin derivatives on their merits as dual glucosylceramide synthase/neutral glucosylceramidase inhibitors. Building on our previous work, we synthesized a series of d-gluco and l-ido-configured iminosugars N-modified with a variety of hydrophobic functional groups. We found that iminosugars featuring N-pentyloxymethylaryl substituents are considerably more potent inhibitors of glucosylceramide synthase than their aliphatic counterparts. In a next optimization round, we explored a series of biphenyl-substituted iminosugars of both configurations (d-gluco and l-ido) with the aim to introduce structural features known to confer metabolic stability to drug-like molecules. From these series, two sets of molecules emerge as lead series for further profiling. Biphenyl-substituted l-ido-configured deoxynojirimycin derivatives are selective for glucosylceramidase and the nonlysosomal glucosylceramidase, and we consider these as leads for the treatment of neuropathological lysosomal storage disorders. Their d-gluco-counterparts are also potent inhibitors of intestinal glycosidases, and because of this characteristic, we regard these as the prime candidates for type 2 diabetes therapeutics.

  DOI：

  10.1021/jm501181z

文献信息

• Identification and Development of Biphenyl Substituted Iminosugars as Improved Dual Glucosylceramide Synthase/Neutral Glucosylceramidase Inhibitors
  作者：Amar T. Ghisaidoobe、Richard J. B. H. N. van den Berg、Saleem S. Butt、Anneke Strijland、Wilma E. Donker-Koopman、Saskia Scheij、Adrianus M. C. H. van den Nieuwendijk、Gerrit-Jan Koomen、Arnold van Loevezijn、Mark Leemhuis、Tom Wennekes、Mario van der Stelt、Gijsbert A. van der Marel、Constant A. A. van Boeckel、Johannes M. F. G. Aerts、Herman S. Overkleeft

  DOI：10.1021/jm501181z

  日期：2014.11.13

  This work details the evaluation of a number of N-alkylated deoxynojirimycin derivatives on their merits as dual glucosylceramide synthase/neutral glucosylceramidase inhibitors. Building on our previous work, we synthesized a series of d-gluco and l-ido-configured iminosugars N-modified with a variety of hydrophobic functional groups. We found that iminosugars featuring N-pentyloxymethylaryl substituents are considerably more potent inhibitors of glucosylceramide synthase than their aliphatic counterparts. In a next optimization round, we explored a series of biphenyl-substituted iminosugars of both configurations (d-gluco and l-ido) with the aim to introduce structural features known to confer metabolic stability to drug-like molecules. From these series, two sets of molecules emerge as lead series for further profiling. Biphenyl-substituted l-ido-configured deoxynojirimycin derivatives are selective for glucosylceramidase and the nonlysosomal glucosylceramidase, and we consider these as leads for the treatment of neuropathological lysosomal storage disorders. Their d-gluco-counterparts are also potent inhibitors of intestinal glycosidases, and because of this characteristic, we regard these as the prime candidates for type 2 diabetes therapeutics.