(E)-1,3,7-trimethyl-8-(3-methylstyryl)-1H-purine-2,6(3H,7H)-dione

• 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: (E)-1,3,7-trimethyl-8-(3-methylstyryl)-1H-purine-2,6(3H,7H)-dione
• 英文别名: 1,3,7-trimethyl-8-[(E)-2-(3-methylphenyl)ethenyl]purine-2,6-dione
• 化学式: C₁₇H₁₈N₄O₂
• 分子量: 310.356
• InChiKey: SVSAAHQERJSGNZ-CMDGGOBGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  58.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  5,6-二氨基-1,3-二甲基脲嘧啶 在 盐酸 、 potassium carbonate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.75h， 生成 (E)-1,3,7-trimethyl-8-(3-methylstyryl)-1H-purine-2,6(3H,7H)-dione
  参考文献：
  名称：

  Inhibition of monoamine oxidase B by analogues of the adenosine A2A receptor antagonist (E)-8-(3-chlorostyryl)caffeine (CSC)

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2006.01.011

文献信息

• Palladium-catalyzed C–H olefination of uracils and caffeines using molecular oxygen as the sole oxidant
  作者：Xinyu Zhang、Lv Su、Lin Qiu、Zhenwei Fan、Xiaofeng Zhang、Shen Lin、Qiufeng Huang

  DOI：10.1039/c7ob00616k

  日期：——

  The palladium-catalyzed oxidative C–H olefination of uracils or caffeines with alkenes using an atmospheric pressure of molecular oxygen as the sole oxidant has been disclosed. This novel strategy offers an efficient and environmentally friendly method to biologically important C5-alkene uracil derivatives or C8-alkene caffeine derivatives.

  已经公开了使用大气压下的分子氧作为唯一的氧化剂，钯催化尿烷或咖啡因与烯烃的钯催化氧化CH烯化反应。这种新颖的策略为生物学上重要的C5-烯烃尿嘧啶衍生物或C8烯烃咖啡因衍生物提供了一种有效且环保的方法。
• SELECTIVE A2A RECEPTOR ANTAGONISTS FOR THE TREATMENT OF AURICULAR FIBRILLATION
  申请人：Proyecto de Biomedicina Cima, S.L.

  公开号：EP1949903B1

  公开（公告）日：2012-04-18
• COMBINATION THERAPY TO IMPROVE DRUG EFFICIENCY
  申请人：Ding Rui

  公开号：US20120052005A1

  公开（公告）日：2012-03-01

  Compositions and methods for increasing drug bioavailability and/or preventing multi-drug resistance through inhibition of ABCG2 by xanthine compounds are disclosed.
• 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.