7-(2-bromoethyl)-8-(bromomethyl)-1,3-dimethylpurine-2,4-dione | 1624255-71-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 7-(2-bromoethyl)-8-(bromomethyl)-1,3-dimethylpurine-2,4-dione
• 英文别名: 7-(2-bromoethyl)-8-bromo-1,3-dimethylpurine-2,4-dione
• CAS: 1624255-71-5
• 化学式: C₁₀H₁₂Br₂N₄O₂
• 分子量: 380.039
• InChiKey: FLHCEUUAEVWFHS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.72
• 重原子数：
  18.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  61.82
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  7-(2-bromoethyl)-8-(bromomethyl)-1,3-dimethylpurine-2,4-dione 在 copper(l) iodide 、 四(三苯基膦)钯 、 N,N-二异丙基乙胺 作用下， 以 乙二醇二甲醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 8-(3-(3-methoxyphenyl)prop-2-ynyl)-1,3-dimethyl-6,7,8,9-tetrahydropyrazino-[2,1-f]purine-2,4(1H,3H)-dione
  参考文献：
  名称：

  8-Substituted 1,3-dimethyltetrahydropyrazino[2,1-f]purinediones: Water-soluble adenosine receptor antagonists and monoamine oxidase B inhibitors

  摘要：

  Multitarget approaches, i.e., addressing two or more targets simultaneously with a therapeutic agent, are hypothesized to offer additive therapeutic benefit for the treatment of neurodegenerative diseases. Validated targets for the treatment of Parkinson's disease are, among others, the A(2A) adenosine receptor (AR) and the enzyme monoamine oxidase B (MAO-B). Additional blockade of brain A(1) ARs may also be beneficial. We recently described 8-benzyl-substituted tetrahydropyrazino[2,1-f]purinediones as a new lead structure for the development of such multi-target drugs. We have now designed a new series of tetrahydropyrazino[2,1-f]purinediones to extensively explore their structure-activity-relationships. Several compounds blocked human and rat A(1) and A(2A)ARs at similar concentrations representing dual A(1)/A(2A) antagonists with high selectivity versus the other AR subtypes. Among the best dual A(1)/A(2A)AR antagonists were 8-(3-(4-chlorophenyl)propy1)-1,3-dimethyl-6,7,8,9-tetrahydropyrazino[2,1-flpurine-2,4(1H,3H)-dione (41,K-i human A(1): 65.5 nM, A(2A): 230 nM; K-1 rat A(1): 352 nM, A(2A): 316 nM) and 1,3-dimethy1-84(2(thiophen-2-yl)thiazol-4-y1)methyl)-6,7,8,9-tetrahydropyrazino[2,1-fjpurine-2,4(1H,3H)-dione (57, K-i human A(1): 642 nM, A(2A): 203 nM; K-i rat A(1): 166 nM, A(2A): 121 nM). Compound 57 was found to be well water-soluble (0.7 mg/mL) at a physiological pH value of 7.4. One of the new compounds showed triple -target inhibition: (R)-1,3-dimethy1-8-(2,1,3,4-tetrahydronaphthalen-1-y1)-6,7,8,9-tetrahydropyrazino[2,1-Apurine-2,4(1H,3H)-dione (49) was about equipotent at A(1) and A(2A)ARs and at MAO-B (K-i human A(1): 393 nM, human A(2A): 595 nM, IC50 human MAO-B: 210 nM) thus allowing future in vivo explorations of the intended multi-target approach. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.09.003
• 作为产物：
  描述：

  7-(2-bromoethyl)-8-(hydroxymethyl)-1,3-dimethyl-1H-purine-2,6(3H,7H)-dione 在 三溴化磷 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 7-(2-bromoethyl)-8-(bromomethyl)-1,3-dimethylpurine-2,4-dione
  参考文献：
  名称：

  8-苄基四氢吡嗪并[2,1-f]嘌呤二酮：水溶性三环黄嘌呤衍生物作为神经退行性疾病的多靶点药物

  摘要：

  8-苄基取代的四氢吡嗪并[ 2,1 - f ]嘌呤二酮被设计为在四氢吡嗪环中包含碱性氮原子的三环黄嘌呤衍生物，以提高水溶性。制备了69种衍生物的文库，并在放射性配体结合研究中评估了腺苷受体（AR）亚型及其抑制单胺氧化酶（MAO）的能力。确定了有效的双靶标定向A 1 / A 2A腺苷受体拮抗剂。几种化合物显示出三重靶标抑制作用。最好的化合物之一是8-（2,4-二氯-5-氟苄基）-1,3-二甲基-6,7,8,9-四氢吡嗪并[2,1 - f ]嘌呤-2,4（1 H，3 H）-dione（72）（人类AR：K i  A 1 217 n M，A 2A 233 n M；IC 50 MAO-B：508 n M）。二氯化化合物36 [8-（3,4-二氯苄基）-1,3-二甲基-6,7,8,9-四氢吡嗪并[2,1 - f ]嘌呤-2,4（1 H，3 H）-二酮]被认为是大鼠中最佳的三靶标药物（K i  A 1

  DOI：

  10.1002/cmdc.201402082