4-((2R,3R,4R)-3,4-bis(benzyloxy)-2-((benzyloxy)methyl)pyrrolidin-1-yl)butan-1-amine | 1450833-88-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-((2R,3R,4R)-3,4-bis(benzyloxy)-2-((benzyloxy)methyl)pyrrolidin-1-yl)butan-1-amine
• 英文别名: (4-{(2R,3R,4R)-3,4-bis(benzyloxy)-2-[(benzyloxy)methyl]pyrrolidin-1yl}butyl)amine
• CAS: 1450833-88-1
• 化学式: C₃₀H₃₈N₂O₃
• 分子量: 474.643
• InChiKey: OPXDOZSPGMYKLY-IDZRBWSNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  35.0
• 可旋转键数：
  14.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  56.95
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  4-((2R,3R,4R)-3,4-bis(benzyloxy)-2-((benzyloxy)methyl)pyrrolidin-1-yl)butan-1-amine 在 盐酸 、 palladium on carbon 、 氢气 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 水 为溶剂， 反应 5.0h， 生成 N-(4-((2R,3R,4R)-3,4-dihydroxy-2-(hydroxymethyl)pyrrolidin-1-yl)butyl)-2-(9H-fluoren-9-yl)acetamide
  参考文献：
  名称：

  亚氨基糖中N-取代的快速修饰：新型β-葡萄糖脑苷脂酶抑制剂和戈谢病药理伴侣的开发

  摘要：

  描述了快速发现β-葡萄糖脑苷脂酶（GCase）抑制剂和戈谢病的药理伴侣蛋白。的Ñ -氨基丁基基于DNJ-亚氨基糖合成并与各种羧酸缀合，以产生Ñ -diversely取代的亚氨基糖的基于库。已发现该文库的几个成员是GCase的纳摩尔范围抑制剂。抑制常数K i发现最有效的为71 nM。尽管这些新分子在来自Gaucher患者来源的细胞系的N370S成纤维细胞中显示出合理的伴侣活性（1.5至1.9倍），但同时伴随着细胞α-葡萄糖苷酶活性的下降，这可能会限制其进一步的治疗潜力。接下来，将新开发的N-取代基与吡咯烷基支架组装在一起，以产生新的分子用于进一步评估。新的2,5-二脱氧-2,5-亚氨基d -mannitol（DMDP）基亚氨基糖22被发现显示出令人满意的活性的陪伴通过以增强的GCase活性的戈谢N370S细胞系2.2倍，而没有损害蜂窝α-葡萄糖苷酶活性。

  DOI：

  10.1016/j.bmc.2013.06.054
• 作为产物：
  描述：

  (2R,3R,4R)-1-(4-azidobutyl)-3,4-bis(benzyloxy)-2-[(benzyloxy)methyl]pyrrolidine 在 三苯基膦 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 16.0h， 以84%的产率得到4-((2R,3R,4R)-3,4-bis(benzyloxy)-2-((benzyloxy)methyl)pyrrolidin-1-yl)butan-1-amine
  参考文献：
  名称：

  Dual targeting of PTP1B and glucosidases with new bifunctional iminosugar inhibitors to address type 2 diabetes

  摘要：

  The diffusion of type 2 diabetes (T2D) throughout the world represents one of the most important health problems of this century. Patients suffering from this disease can currently be treated with numerous oral anti-hyperglycaemic drugs, but none is capable of reproducing the physiological action of insulin and, in several cases, they induce severe side effects. Developing new anti-diabetic drugs remains one of the most urgent challenges of the pharmaceutical industry. Multi-target drugs could offer new therapeutic opportunities for the treatment of T2D, and the reported data on type 2 diabetic mice models indicate that these drugs could be more effective and have fewer side effects than mono-target drugs. alpha-Glucosidases and Protein Tyrosine Phosphatase 1B (PTP1B) are considered important targets for the treatment of T2D: the first digest oligo- and disaccharides in the gut, while the latter regulates the insulin-signaling pathway. With the aim of generating new drugs able to target both enzymes, we synthesized a series of bifunctional compounds bearing both a nitro aromatic group and an iminosugar moiety. The results of tests carried out both in vitro and in a cell-based model, show that these bifunctional compounds maintain activity on both target enzymes and, more importantly, show a good insulin-mimetic activity, increasing phosphorylation levels of Akt in the absence of insulin stimulation. These compounds could be used to develop a new generation of anti-hyperglycemic drugs useful for the treatment of patients affected by T2D.

  DOI：

  10.1016/j.bioorg.2019.03.053