BOC-glycine-4-phenylpiperazin-1-ylamide | 1020083-62-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: BOC-glycine-4-phenylpiperazin-1-ylamide
• 英文别名: tert-butyl N-[2-oxo-2-(4-phenylpiperazin-1-yl)ethyl]carbamate
• CAS: 1020083-62-8
• 化学式: C₁₇H₂₅N₃O₃
• 分子量: 319.404
• InChiKey: WLJPSMVUVCJIBN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  61.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  BOC-glycine-4-phenylpiperazin-1-ylamide 在 三氟乙酸 作用下， 反应 1.0h， 以60%的产率得到glycine-4-phenylpiperazin-1-ylamide trifluoroacetate
  参考文献：
  名称：

  Malawska, Barbara; Kulig, Katarzyna; Gajda, Justyna, Acta poloniae pharmaceutica, 2007, vol. 64, # 2, p. 127 - 137

  摘要：

  DOI：
• 作为产物：
  描述：

  BOC-甘氨酸 、 N-苯基哌嗪 在 N,N'-羰基二咪唑 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以97%的产率得到BOC-glycine-4-phenylpiperazin-1-ylamide
  参考文献：
  名称：

  Malawska, Barbara; Kulig, Katarzyna; Gajda, Justyna, Acta poloniae pharmaceutica, 2007, vol. 64, # 2, p. 127 - 137

  摘要：

  DOI：

文献信息

• 1,3-Dialkyl-substituted tetrahydropyrimido[1,2-f]purine-2,4-diones as multiple target drugs for the potential treatment of neurodegenerative diseases
  作者：Pierre Koch、Rhalid Akkari、Andreas Brunschweiger、Thomas Borrmann、Miriam Schlenk、Petra Küppers、Meryem Köse、Hamid Radjainia、Jörg Hockemeyer、Anna Drabczyńska、Katarzyna Kieć-Kononowicz、Christa E. Müller

  DOI：10.1016/j.bmc.2013.09.044

  日期：2013.12

  Adenosine receptors and monoamine oxidases are drug targets for neurodegenerative diseases such as Parkinson's and Alzheimer's disease. In the present study we prepared a library of 55 mostly novel tetrahydropyrimido[2,1-f]purinediones with various substituents in the 1- and 3-position (1,3-dimethyl, 1,3-diethyl, 1,3-dipropyl, 1-methyl-3-propargyl) and broad variation in the 9-position. A synthetic strategy to obtain 3-propargyl-substituted tetrahydropyrimido[2,1-f]purinedione derivatives was developed. The new compounds were evaluated for their interaction with all four adenosine receptor subtypes and for their ability to inhibit monoamine oxidases (MAO). Introduction of mono-or di-chloro-substituted phenyl, benzyl or phenethyl residues at N9 of the 1,3-dimethyl series led to the discovery of a novel class of potent MAO-B inhibitors, the most potent compound being 9-(3,4-dichlorobenzyl)-1,3-dimethyl-6,7,8,9-tetrahydropyrimido[1,2-f]purine-2,4(1H,3H)-dione (21g, IC50 human MAO-B: 0.0629 mu M), which displayed high selectivity versus the other investigated targets. Potent dually active A(1)/A(2A) adenosine receptor antagonists were identified, for example, 9-benzyl-1-methyl-3-propargyl-6,7,8,9-tetrahydropyrimido[1,2-f]purine-2,4(1H,3H)dione (19f, K-i, human receptors, A(1): 0.249 mu M, A(2A): 0.253 mu M). Several compounds showed triple-target inhibition, the best compound being 9-(2-methoxybenzyl)-1-methyl-3-(prop-2-ynyl)-6,7,8,9-tetrahydro pyrimido [1,2-f]purine-2,4(1H,3H)-dione (19g, K-i A(1): 0.605 mu M, K-i A(2A): 0.417 mu M, IC50 MAO-B: 1.80 mu M). Compounds inhibiting several different targets involved in neurodegeneration may exhibit additive or even synergistic effects in vivo. (C) 2013 Elsevier Ltd. All rights reserved.