ethyl 2-(8-bromo-1,3-dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-7-yl)acetate | 52943-73-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: ethyl 2-(8-bromo-1,3-dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-7-yl)acetate
• 英文别名: ethyl 2-(8-bromo-1,3-dimethyl-2,6-dioxo-2,3-dihydro-1H-purin-7(6H)-yl)acetate；ethyl 2-[8-bromo-1,3-dimethyl-2,6-dioxo-2,3-dihydro-1H-purin-7(6H)-yl]acetate；(8-bromo-1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-purin-7-yl)-acetic acid ethyl ester；(8-Brom-1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-purin-7-yl)-essigsaeure-aethylester；Ethyl 2-(8-bromo-1,3-dimethyl-2,6-dioxopurin-7-yl)acetate
• CAS: 52943-73-4
• 化学式: C₁₁H₁₃BrN₄O₄
• 分子量: 345.153
• InChiKey: KOUDKMQKKXZWLY-UHFFFAOYSA-N

物化性质

• 熔点：
  153-153.5 °C
• 沸点：
  501.1±60.0 °C(Predicted)
• 密度：
  1.74±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  84.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 2-(8-bromo-1,3-dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-7-yl)acetate 在 盐酸 作用下， 生成 2-(8-bromo-1,3-dimethyl-2,6-dioxo-2,3-dihydro-1H-purin-7(6H)-yl)acetic acid
  参考文献：
  名称：

  Cacace et al., Annali di Chimica, 1956, vol. 46, p. 99,102,104

  摘要：

  DOI：
• 作为产物：
  描述：

  8-溴茶碱 、 溴乙酸乙酯 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 ethyl 2-(8-bromo-1,3-dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-7-yl)acetate
  参考文献：
  名称：

  [EN] PURINE DIONES AS WNT PATHWAY MODULATORS
  [FR] PURINE DIONES UTILISÉES COMME MODULATEURS DE LA VOIE WNT

  摘要：

  本发明涉及通用结构（I）化合物在调节Wnt信号通路中的应用。其中，R1、R2、R3、R4和R5各自独立地为H或烷基；D选自由H、卤素、烷基、环烷基、芳基和二烷基氨基组成的组，每个（除H和卤素外）可被选为取代；Ar是芳基或杂芳基，可被选为取代；Cy是芳基、杂芳基或至少含有一个杂原子的饱和环，每个可被选为取代；n是从1到3的整数。

  公开号：

  WO2014189466A1

文献信息

• Novel amide derivatives of 1,3-dimethyl-2,6-dioxopurin-7-yl-alkylcarboxylic acids as multifunctional TRPA1 antagonists and PDE4/7 inhibitors: A new approach for the treatment of pain
  作者：Grażyna Chłoń-Rzepa、Marietta Ślusarczyk、Agnieszka Jankowska、Alicja Gawalska、Adam Bucki、Marcin Kołaczkowski、Artur Świerczek、Krzysztof Pociecha、Elżbieta Wyska、Małgorzata Zygmunt、Grzegorz Kazek、Kinga Sałat、Maciej Pawłowski

  DOI：10.1016/j.ejmech.2018.09.021

  日期：2018.10

  promising multifunctional TRPA1 antagonist and PDE4B/7A dual inhibitor with IC50 values in the range of that of the reference rolipram and BRL-50481, respectively. Compound 36 as a combined TRPA1/PDE4B/PDE7A ligand was characterized by a distinct binding mode in comparison to 16 and 27, in the given protein targets. The inhibition of both cAMP-specific PDE isoenzymes resulted in a strong anti-TNF-α effect

  合成并分析了一系列使用基于结构的计算方法设计的1,3-二甲基-2,6-二氧杂嘌呤-7-基-烷基羧酸的新型酰胺衍生物，以评估其阻断人TRPA1通道和抑制PDE4B /的能力。 7A活动。我们鉴定了与HC-030031相比，对TRPA1具有更高效力的化合物16和27。反过来，化合物36是最有前途的多功能TRPA1拮抗剂和PDE4B / 7A双重抑制剂，其IC 50值分别在参考咯利普兰和BRL-50481的范围内。化合物36作为TRPA1 / PDE4B / PDE7A的组合配体，其特征在于与16和1627，在给定的蛋白质靶标上。两种cAMP特异性PDE同工酶的抑制作用在体内可产生36 种强的抗TNF-α作用。此外，在疼痛和发炎的动物模型（小鼠中的福尔马林测试和大鼠中的角叉菜胶诱发的爪水肿）中观察到了强效的36消炎和镇痛效果。该化合物在化疗诱导的小鼠周围神经病变的早期也显示出显着的抗痛觉过敏特性
• Synthesis of 8-alkoxy-1,3-dimethyl-2, 6-dioxopurin-7-yl-substituted acetohydrazides and butanehydrazides as analgesic and anti-inflammatory agents
  作者：Grażyna Chłoń-Rzepa、Agnieszka W. Jankowska、Małgorzata Zygmunt、Krzysztof Pociecha、Elżbieta Wyska

  DOI：10.1515/hc-2015-0100

  日期：2015.10.1

  A series of new 8-alkoxy-1,3-dimethyl-2,6-dioxopurin-7-yl-substituted acetohydrazides and butanehydrazides 6–12 was synthesized and evaluated for the analgesic activity in two in vivo models: the writhing syndrome and the hot-plate tests. Among the investigated derivatives, compounds with N′-arylidenehydrazide moiety 9–12 show analgesic activity significantly higher than that of acetylsalicylic acid, which may indicate the importance of this structural element for analgesic properties. The lack of the activity in the hot-plate test may suggest that the analgesic activity of the newly synthesized compounds is mediated by a peripheral mechanism. The selected compounds 7 and 12 inhibit tumor necrosis factor α production in a rat model of lipopolysaccharide-induced endotoxemia, similarly to theophylline, which may confirm their anti-inflammatory properties.

  合成了一系列新的8-烷氧基-1,3-二甲基-2,6-二氧杂嘌呤-7-基取代乙酰肼和丁酰肼化合物6–12，并在两个in vivo模型中评估其镇痛活性：扭体综合征和热板测试。在所研究的衍生物中，具有N′-芳香亚甲基肼基的化合物9–12的镇痛活性明显高于乙酰水杨酸，这可能表明这种结构元素对镇痛性质的重要性。在热板测试中缺乏活性可能表明新合成的化合物的镇痛活性是通过外周机制介导的。选择的化合物7和12在脂多糖诱导的内毒素血症大鼠模型中抑制肿瘤坏死因子α的产生，类似于茶碱，这可能证实它们的抗炎性质。

• Purine Diones As Wnt Pathway Modulators
  申请人：AGENCY FOR SCIENCE, TECHNOLOGY AND RESEARCH

  公开号：US20160090386A1

  公开（公告）日：2016-03-31

  The invention relates to the use of compounds of general structure (I) in modulation of the Wnt pathway [Formula should be inserted here] wherein R 1 , R 2 , R 3 , R 4 and R 5 are each, independently, H or an alkyl group; D is selected from the group consisting of H, halogen, alkyl, cycloalkyl, aryl, and dialkylamino, each (other than H and halogen) being optionally substituted; Ar is an aryl or heteroaryl group, optionally substituted; Cy is an aryl, heteroaryl or a saturated ring containing at least one heteroatom, each being optionally substituted; and n is an integer from 1 to 3.

  本发明涉及一般结构（I）化合物在调节Wnt途径中的使用[应在此处插入公式]其中R1、R2、R3、R4和R5各自独立地为H或烷基；D从H、卤素、烷基、环烷基、芳基和二烷基氨基等中选择，除H和卤素外，每种选择都可以被选择性地取代；Ar是芳基或杂芳基，可以被选择性地取代；Cy是芳基、杂芳基或至少含有一个杂原子的饱和环，每个都可以被选择性地取代；n是1到3的整数。
• Purine diones as Wnt pathway modulators
  申请人：Agency for Science, Technology and Research

  公开号：US10472360B2

  公开（公告）日：2019-11-12

  The invention relates to the use of compounds of general structure (I) in modulation of the Wnt pathway [Formula should be inserted here] wherein R1, R2, R3, R4 and R5 are each, independently, H or an alkyl group; D is selected from the group consisting of H, halogen, alkyl, cycloalkyl, aryl, and dialkylamino, each (other than H and halogen) being optionally substituted; Ar is an aryl or heteroaryl group, optionally substituted; Cy is an aryl, heteroaryl or a saturated ring containing at least one heteroatom, each being optionally substituted; and n is an integer from 1 to 3.

  本发明涉及一般结构(I)化合物在调节 Wnt 通路中的用途[此处应插入式子] 其中 R1、R2、R3、R4 和 R5 各自独立地为 H 或烷基； D 选自 H、卤素、烷基、环烷基、芳基和二烷基氨基组成的组，每种基团（H 和卤素除外）均被任选取代；Ar 是芳基或杂芳基，任选被取代；Cy 是芳基、杂芳基或含有至少一个杂原子的饱和环，每种基团均被任选取代；以及 n 是 1 至 3 的整数。
• Synthesis, 5-HT1A and 5-HT2A receptor affinity of new 1-phenylpiperazinylpropyl derivatives of purine-2,6- and pyrrolidine-2,5-diones
  作者：Maciej Pawłowski、Grażyna Chłoń、Jolanta Obniska、Alfred Zejc、Sijka Charakchieva-Minol、Maria J Mokrosz

  DOI：10.1016/s0014-827x(00)00069-0

  日期：2000.7

  Two series of 1-phenylpiperazinylpropyl derivatives 10, 11, 16, 17 and 19-24, structurally related to previously described 5-HT1A or 5-HT2A ligands 4 and 1, respectively, were synthesized and their binding properties were determined. Structural modifications which involved 1,3-diazepine ring opening in 4 (compounds 10, 11, 15, 16) and replacement of spiroalkyl moiety in 1 by aryl substituent (19-24) did not improve binding affinity and selectivity of the tested compounds. The results showed, however, that the diazepine ring present in 4 or spiroalkyl ring in 1 are important for high 5-HT1A or 5-HT2A binding affinity and selectivity of these compounds. (C) 2000 Elsevier Science S.A. All rights reserved.