1,3-dimethyl-5-nitro-6-styryluracil | 59119-41-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1,3-dimethyl-5-nitro-6-styryluracil
• 英文别名: 1,3-dimethyl-5-nitro-6-styryl-1H-pyrimidine-2,4-dione；1,3-Dimethyl-5-nitro-6-(2-phenylethenyl)pyrimidine-2,4-dione
• CAS: 59119-41-4
• 化学式: C₁₄H₁₃N₃O₄
• 分子量: 287.275
• InChiKey: LKYSNWSHWDHNJX-UHFFFAOYSA-N

物化性质

• 熔点：
  196-198 °C(Solv: acetic acid (64-19-7); water (7732-18-5))
• 沸点：
  406.3±55.0 °C(Predicted)
• 密度：
  1.38±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  86.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1,3-dimethyl-5-nitro-6-styryluracil 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 生成 5-amino-1,3-dimethyl-6-phenethyluracil
  参考文献：
  名称：

  Nishigaki, Sadao; Kanamori, Yukako; Senga, Keitaro, Chemical and pharmaceutical bulletin, 1980, vol. 28, # 5, p. 1636 - 1641

  摘要：

  DOI：
• 作为产物：
  描述：

  1,3,4-三甲基尿嘧啶 在 哌啶 、 硫酸 、 硝酸 作用下， 以 乙醇 为溶剂， 反应 5.0h， 生成 1,3-dimethyl-5-nitro-6-styryluracil
  参考文献：
  名称：

  Synthesis and Structure-Activity Relationships of Deazaxanthines: Analogs of Potent A1- and A2-Adenosine Receptor Antagonists

  摘要：

  A set of 22 9-deazaxanthines (pyrrolo[3,2-d]pyrimidine-2,4-diones) and three 7-deazaxanthines (pyrrolo[2,3-d] pyrimidine-2,4-diones) with various substituents in the 1-, 3-, 7- or 9-, and 8-positions was synthesized and investigated in A1 and A2a adenosine receptor binding assays at rat brain cortical membranes and rat brain striatal membranes, respectively. 9-Deazaxanthines showed structure-activity relationships that were similar to those of xanthines. They were about equipotent to the corresponding xanthines at A2a adenosine receptors. 9-Deazaxanthines were generally at least 2-3-fold more potent than xanthines at A1 receptors and therefore exhibited higher A1 selectivities compared to the xanthines. 1,3-Dimethyl-8-(2-naphthyl)-9-deazaxanthine (19e) showed high affinty (K-i = 26 nM) and selectivity for A1 adenosine receptors. A hydroxyl function at N7 of 9-deazaxanthines was unfavorable for A1 and A2a receptor binding. 7-Deazaxanthines were considerably less potent compared to xanthines and to 9-deazaxanthines at both receptor subtypes.

  DOI：

  10.1021/jm00036a019

文献信息

• Syntheses and properties of 3-hydroxy-4,6-dimethylpyrrolo(3,2-d)pyrimidine-5,7(4H,6H)-dione (9-hydroxy-9-deazatheophylline) derivatives.
  作者：FUMIO YONEDA、MIYUKI MOTOKURA、MUTSUKO KAMISHIMOTO、TOMOHISA NAGAMATSU、MASAKI OTAGIRI、KANETO UEKAMA、MASAYUKI TAKAMOTO

  DOI：10.1248/cpb.30.3187

  日期：——

  Treatment of 1, 3, 6-trimethyl-5-nitrouracil with aryl aldehydes in the presence of piperidine results in condensation to the 5-nitro-6-styryluracil derivatives, followed by intramolecular cyclization including piperidine-catalyzed oxidation-reduction to give rise to the corresponding 3-hydroxy-4, 6-dimethylpyrrolo [3, 2-d] pyrimidine-5, 7 (4H, 6H)-dione (9-hydroxy-9-deazatheophylline) derivatives in a single step. Some properties of these compounds and an X-ray crystal structure determination of 8-(p-chlorophenyl)-9-methoxy-7-methyl-9-deazatheophylline are described.

  1，3，6-三甲基-5-硝基尿嘧啶与芳基醛在哌啶存在下进行处理，缩合生成 5-硝基-6-苯乙烯基尿嘧啶衍生物、然后通过分子内环化（包括哌啶催化的氧化还原），一步生成相应的 3-羟基-4, 6-二甲基吡咯并[3, 2-d] 嘧啶-5, 7 (4H, 6H)-二酮（9-羟基-9-去氮茶碱）衍生物。文中介绍了这些化合物的一些特性以及 8-（对氯苯基）-9-甲氧基-7-甲基-9-去氮茶碱的 X 射线晶体结构。
• Pyrimidine derivatives and related compounds. Part 36. Nucleophilic addition reaction of a cyanide lon to 6-substituted 1,3-dimethyl-5-nitrouracils. Synthesis of 5,6-dihydrouracil and 5,6-dihydrocyclo-thymine derivatives
  作者：Kosaku Hirota、Yoshihiro Yamada、Tetsuji Asao、Shigeo Senda

  DOI：10.1039/p19810001896

  日期：——

  6-Substituted 1,3-dimethyl-5-nitrouracils (3a–c) react with potassium cyanide to give stereospecifically the 6-cyano-5-nitro-5,6-dihydrouracils (4a–c). Reaction of 6-bromomethyl-1,3-dimethyl-5-nitrouracil (7) with potassium cyanide gives 6-cyano-1,3-dimethyl-5-nitro-5,6-dihydrocyclothymine (8). The structures of the 5,6-dihydrouracils (4a–c) and the cyclothymine (8) were clarified using 1H and 13C

  6-取代的1,3-二甲基-5-硝基尿嘧啶（3a–c）与氰化钾反应生成立体定向的6-氰基-5-硝基-5,6-二氢尿嘧啶（4a–c）。使6-溴甲基-1,3-二甲基-5-硝基尿嘧啶（7）与氰化钾反应，得到6-氰基-1,3-二甲基-5-硝基-5,6-二氢环胸腺嘧啶（8）。使用1 H和13 C核磁共振波谱对5，6-二氢尿嘧啶（4a–c）和环胸腺嘧啶（8）的结构进行了澄清。
• NEW SYNTHESIS OF 1,3-DIMETHYL-7-HYDROXYPYRROLO[3,2-<i>d</i>]PYRIMIDINE-2,4(1<i>H</i>,3<i>H</i>)-DIONES (9-HYDROXY-9-DEAZATHEOPHYLLINES)
  作者：Fumio Yoneda、Miyuki Motokura、Masaki Otagiri

  DOI：10.1246/cl.1981.1273

  日期：1981.9.5

  Treatment of 5-nitro-1,3,6-trinitrouracil with aryl aldehydes in the presence of piperidine causes the condensation to the 5-nitro-6-styryluracil derivatives, followed by the intramolecular cyclization including piperidine-catalyzed oxidation-reduction to give rise to the corresponding 1,3-dimethyl-7-hydroxypyrrolo[3,2-d]pyrimidine-2,4(1H,3H)-dione (9-hydroxy-9-deazatheophylline) derivatives in a single step. Some properties of these compounds are discussed.

  在有哌啶存在的情况下，5-硝基-1,3,6-三硝基尿嘧啶与芳基醛处理后会缩合成 5-硝基-6-苯乙烯基尿嘧啶衍生物、然后通过分子内环化（包括哌啶催化的氧化还原），一步生成相应的 1,3-二甲基-7-羟基吡咯并[3,2-d]嘧啶-2,4(1H,3H)-二酮（9-羟基-9-去氮茶碱）衍生物。本文讨论了这些化合物的一些特性。
• 1,3-Dialkyl-8-(hetero)aryl-9-OH-9-deazaxanthines as potent A2B adenosine receptor antagonists: Design, synthesis, structure–affinity and structure–selectivity relationships
  作者：Angela Stefanachi、Orazio Nicolotti、Francesco Leonetti、Saverio Cellamare、Francesco Campagna、Maria Isabel Loza、Jose Manuel Brea、Fernando Mazza、Enrico Gavuzzo、Angelo Carotti

  DOI：10.1016/j.bmc.2008.09.067

  日期：2008.11

  A number of 1,3-dialkyl-8-(hetero)aryl-9-OH-9-deazaxanthines were prepared and evaluated as ligands of recombinant human adenosine receptors (hARs). Several 1,3-dipropyl derivatives endowed with nano-molar binding affinity at hA(2B) receptors, but poor selectivity over hA(2A), hA(1) and hA(3) AR subtypes were identified. A comparison with the corresponding 7-OH- and 7,9-unsubstituted-deazaxanthines revealed that 9-OH-9-deazaxanthines are more potent hA(2B) ligands with lower partition coefficients and higher water solubility compared to the other two congeneric classes of deazaxanthines. An optimization of the para-substituent of the 8-phenyl ring of 9-OH-9-deazaxanthines led to the discovery of compound 38, which exhibited outstanding hA(2B) affinity (Ki = 1.0 nM), good selectivity over hA(2A), hA(1) and hA(3) (selectivity indices = 100, 79 and 1290, respectively) and excellent antagonist potency in a functional assay on rat A(2B) (pA(2B) = 9.33). (C) 2008 Published by Elsevier Ltd.
• Synthesis and Structure-Activity Relationships of Deazaxanthines: Analogs of Potent A1- and A2-Adenosine Receptor Antagonists
  作者：Bettina Grahner、Susanne Winiwarter、Wolfgang Lanzner、Christa E. Mueller

  DOI：10.1021/jm00036a019

  日期：1994.5

  A set of 22 9-deazaxanthines (pyrrolo[3,2-d]pyrimidine-2,4-diones) and three 7-deazaxanthines (pyrrolo[2,3-d] pyrimidine-2,4-diones) with various substituents in the 1-, 3-, 7- or 9-, and 8-positions was synthesized and investigated in A1 and A2a adenosine receptor binding assays at rat brain cortical membranes and rat brain striatal membranes, respectively. 9-Deazaxanthines showed structure-activity relationships that were similar to those of xanthines. They were about equipotent to the corresponding xanthines at A2a adenosine receptors. 9-Deazaxanthines were generally at least 2-3-fold more potent than xanthines at A1 receptors and therefore exhibited higher A1 selectivities compared to the xanthines. 1,3-Dimethyl-8-(2-naphthyl)-9-deazaxanthine (19e) showed high affinty (K-i = 26 nM) and selectivity for A1 adenosine receptors. A hydroxyl function at N7 of 9-deazaxanthines was unfavorable for A1 and A2a receptor binding. 7-Deazaxanthines were considerably less potent compared to xanthines and to 9-deazaxanthines at both receptor subtypes.