1,3-dimethyl-8-(E)-styryl-3,7-dihydro-1H-purine-2,6-dione | 147699-92-1

• 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: 1,3-dimethyl-8-(E)-styryl-3,7-dihydro-1H-purine-2,6-dione
• 英文别名: (E)-1,3-dimethyl-8-styryl-1H-purine-2,6(3H,7H)-dione；1,3-dimethyl-8-trans-styryl-3,7-dihydro-purine-2,6-dione；1,3-Dimethyl-8-trans-styryl-3,7-dihydro-purin-2,6-dion；8-Styryltheophyllin；8-Styryltheophylline；1,3-dimethyl-8-[(E)-2-phenylethenyl]-7H-purine-2,6-dione
• CAS: 147699-92-1
• 化学式: C₁₅H₁₄N₄O₂
• 分子量: 282.302
• InChiKey: BTFAUMMRKLKUJP-CMDGGOBGSA-N

物化性质

• 熔点：
  >270 °C
• 沸点：
  547.0±60.0 °C(Predicted)
• 密度：
  1.369±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  69.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1,3-dimethyl-8-(E)-styryl-3,7-dihydro-1H-purine-2,6-dione 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 20.0 ℃ 、344.75 kPa 条件下， 反应 2.0h， 以100%的产率得到NSC 14319
  参考文献：
  名称：

  US2014/275528

  摘要：

  公开号：
• 作为产物：
  描述：

  8-溴茶碱 在 potassium phosphate 、 四(三苯基膦)钯 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 126.0h， 生成 1,3-dimethyl-8-(E)-styryl-3,7-dihydro-1H-purine-2,6-dione
  参考文献：
  名称：

  Vollmann, Karl; Mueller, Christa E., Heterocycles, 2002, vol. 57, # 5, p. 871 - 879

  摘要：

  DOI：

文献信息

• Structure-activity relationships of 8-styrylxanthines as A2-selective adenosine antagonists
  作者：Kenneth A. Jacobson、Carola Gallo-Rodriguez、Neli Melman、Bilha Fischer、Michel Maillard、Andrew van Bergen、Philip J. M. van Galen、Yishai Karton

  DOI：10.1021/jm00062a005

  日期：1993.5

  7-alkylxanthines was synthesized as potential A2-selective adenosine receptor antagonists, and the potency at rat brain A1- and A2-receptors was studied in radioligand binding experiments. At the xanthine 7-position, only small hydrophobic substituents were tolerated in receptor binding. 7-Methyl analogues were roughly 1 order of magnitude more selective for A2 versus A1 receptors than the corresponding 7-H analogues

  合成了一系列取代的1,3,7-烷基黄嘌呤的8-苯乙烯基衍生物作为潜在的A2选择性腺苷受体拮抗剂，并在放射性配体结合实验中研究了对大鼠脑A1和A2受体的效价。在黄嘌呤7位上，受体结合中仅容忍小的疏水取代基。7-甲基类似物对A2和A1受体的选择性比相应的7-H类似物高大约1个数量级。1,3-二甲基黄嘌呤衍生物比相应的1,3-二烯丙基，二乙基或二丙基衍生物倾向于对A2-受体更具选择性。在3-（单取代）和3，5-（二取代）位置上苯环的取代是有利的。1,3，7-三甲基-8-（3-氯苯乙烯基）黄嘌呤是中等效力的（Ki vs [3H] CGS 21680为54 nM）和高度A2选择性（520倍）腺苷拮抗剂。1,3,7-三甲基-8-[（3-羧基-1-氧丙基）氨基]苯乙烯基]黄嘌呤具有很高的A2选择性（250倍），并且具有更高的水溶性（最大19 mM）。1,3-二丙基-7-甲基-8-（3,5-二甲氧基苯乙烯基）黄嘌呤是有效的（Ki
• Inhibition of monoamine oxidase B by selective adenosine A 2A receptor antagonists
  作者：Jacobus P Petzer、Salome Steyn、Kay P Castagnoli、Jiang-Fan Chen、Michael A Schwarzschild、Cornelis J Van der Schyf、Neal Castagnoli

  DOI：10.1016/s0968-0896(02)00648-x

  日期：2003.4

  in the low micro M to nM range. Included in this series is (E)-1,3-diethyl-8-(3,4-dimethoxystyryl)-7-methylxanthine (KW-6002), a potent A(2A) antagonist and neuroprotective agent that is in clinical trials. The results of these studies suggest that MAO-B inhibition may contribute to the neuroprotective potential of A(2A) receptor antagonists such as KW-6002 and open the possibility of designing dual

  对A（2A）受体亚型具有选择性的腺苷受体拮抗剂（A（2A）拮抗剂）正在作为可能的治疗药物，用于对症治疗与帕金森氏病（PD）相关的运动障碍。PD的MPTP小鼠模型中的最新研究结果表明，A（2A）拮抗剂可能具有神经保护特性。由于单胺氧化酶B（MAO-B）抑制剂还增强运动功能并降低MPTP神经毒性，因此我们研究了几种A（2A）拮抗剂和结构相关化合物对MAO-B的抑制作用，以确定是否抑制MAO-B可能有助于观察到的神经保护作用。这些研究的结果已经确定，所有从（E）-8- styrylxanthinyl衍生的A（2A）拮抗剂在体外均表现出显着的MAO-B抑制特性，其K（i）值在低micro M至nM范围内。该系列产品包括（E）-1,3-二乙基-8-（3,4-二甲氧基苯乙烯基）-7-甲基黄嘌呤（KW-6002），这是一种有效的A（2A）拮抗剂和神经保护剂，正在临床试验中。这些研究的结果表明，MAO-B
• SUBSTITUTED XANTHINES AND METHODS OF USE THEREOF
  申请人：Hydra Biosciences, Inc.

  公开号：US20160145257A1

  公开（公告）日：2016-05-26

  Compounds, compositions and methods are described for inhibiting the TRPC5 ion channel and disorders related to TRPC5.

  本文描述了抑制TRPC5离子通道及与TRPC5相关的疾病的化合物、组合物和方法。
• Inhibition of monoamine oxidase B by analogues of the adenosine A2A receptor antagonist (E)-8-(3-chlorostyryl)caffeine (CSC)
  作者：Nevil Vlok、Sarel F. Malan、Neal Castagnoli、Jacobus J. Bergh、Jacobus P. Petzer

  DOI：10.1016/j.bmc.2006.01.011

  日期：2006.5

  The adenosine A(2A) receptor has emerged as a possible target for the treatment of Parkinson's disease (PD). Evidence suggests that antagonism of the A(2A) receptor not only improves the symptoms of the disease but may also protect against the underlying degenerative processes. We have recently reported that several known adenosine A(2A) receptor antagonists (A(2A) antagonists) also are moderate to very potent inhibitors of monoamine oxidase B (MAO-B). The most potent among these was (E)-8-(3-chlorostyryl)caffeine (CSC), a compound frequently used when examining the in vivo pharmacological effects of A(2A) antagonists. Since MAO-B inhibitors are also thought to possess antiparkinsonian properties, dual targeting drugs that block both MAO-B and A(2A) receptors may have enhanced therapeutic potential in the treatment of PD. In this study, we prepared selected analogues of CSC in an attempt to examine specific structural features that may be important for potent MAO-B inhibition. The results of a SAR study established that the potency of MAO-B inhibition by (E)-8-styrylcaffeinyl analogues depends upon the van der Waals volume (V-w), lipophilicity (pi), and the Hammett constant (sigma(m)) of the substituents attached to C-3 of the phenyl ring of the styryl moiety. Potency also varies with substituents attached to C-4 with bulkiness (V-w) and lipophilicity (pi) being the principal substituent descriptors. (c) 2006 Elsevier Ltd. All rights reserved.
• Hager et al., Journal of the American Pharmaceutical Association (1912), 1954, vol. 43, p. 152,154
  作者：Hager et al.

  DOI：——

  日期：——