2-O-(benzylaminocarbonyl)-5-O-benzyl-1,4:3,6-dianhydro-D-glucitol | 1217319-76-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 呋喃类
• 英文名称: 2-O-(benzylaminocarbonyl)-5-O-benzyl-1,4:3,6-dianhydro-D-glucitol
• 英文别名: 2-(Benzylaminocarbonyloxy)-5-O-benzyl-1,4:3,6-dianhydro-D-glucitol；[(3R,3aR,6S,6aR)-3-phenylmethoxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl] N-benzylcarbamate
• CAS: 1217319-76-0
• 化学式: C₂₁H₂₃NO₅
• 分子量: 369.417
• InChiKey: ROBGGBFLUNTBTH-IYWMVGAKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  66
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (3S,3aR,6R,6aR)-6-(benzyloxy)hexahydrofuro[3,2-b]furan-3-ol 、 异氰酸苄酯 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以108.6 mg的产率得到2-O-(benzylaminocarbonyl)-5-O-benzyl-1,4:3,6-dianhydro-D-glucitol
  参考文献：
  名称：

  Isosorbide-based cholinesterase inhibitors; replacement of 5-ester groups leading to increased stability

  摘要：

  Isosorbide-2-carbamate-5-esters are highly potent and selective butyrylcholinesterase inhibitors with potential utility in the treatment of Alzheimer's Disease (AD). They are stable in human plasma but in mouse plasma they undergo hydrolysis at the 5-ester group potentially attenuating in vivo potency. In this paper we explore the role of the 5-position in modulating potency. The focus of the study was to increase metabolic stability while preserving potency and selectivity. Dicarbamates and 5-keto derivatives were markedly less potent than the ester class. The 2-benzylcarbamate-5-benzyl ether was found to be potent (IC50 52 nM) and stable in the presence of mouse plasma and liver homogenate. The compound produces sustained moderate inhibition of mouse butyrylcholinesterase at 1 mg/kg, IP. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.12.052

文献信息

• Isosorbide-based cholinesterase inhibitors; replacement of 5-ester groups leading to increased stability
  作者：Gerald P. Dillon、Joanne M. Gaynor、Denise Khan、Ciaran G. Carolan、Sheila A. Ryder、Juan F. Marquez、Sean Reidy、John F. Gilmer

  DOI：10.1016/j.bmc.2009.12.052

  日期：2010.2

  Isosorbide-2-carbamate-5-esters are highly potent and selective butyrylcholinesterase inhibitors with potential utility in the treatment of Alzheimer's Disease (AD). They are stable in human plasma but in mouse plasma they undergo hydrolysis at the 5-ester group potentially attenuating in vivo potency. In this paper we explore the role of the 5-position in modulating potency. The focus of the study was to increase metabolic stability while preserving potency and selectivity. Dicarbamates and 5-keto derivatives were markedly less potent than the ester class. The 2-benzylcarbamate-5-benzyl ether was found to be potent (IC50 52 nM) and stable in the presence of mouse plasma and liver homogenate. The compound produces sustained moderate inhibition of mouse butyrylcholinesterase at 1 mg/kg, IP. (C) 2009 Elsevier Ltd. All rights reserved.