5-hydroxy-1,3-dimethyl-6-phenyl-1H-pyrrolo[3,2-d]pyrimidine-2,4(3H,5H)-dione | 85102-46-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 5-hydroxy-1,3-dimethyl-6-phenyl-1H-pyrrolo[3,2-d]pyrimidine-2,4(3H,5H)-dione
• 英文别名: 5-hydroxy-1,3-dimethyl-6-phenylpyrrolo[3,2-d]pyrimidine-2,4-dione
• CAS: 85102-46-1
• 化学式: C₁₄H₁₃N₃O₃
• 分子量: 271.276
• InChiKey: DZKNAAFWUMVTAD-UHFFFAOYSA-N

物化性质

• 熔点：
  220-225 °C (decomp)
• 沸点：
  544.5±60.0 °C(Predicted)
• 密度：
  1.39±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  65.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-hydroxy-1,3-dimethyl-6-phenyl-1H-pyrrolo[3,2-d]pyrimidine-2,4(3H,5H)-dione 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以85%的产率得到1,3-dimethyl-6-phenylpyrrolo<3,2-d>pyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  嘧啶衍生物及相关化合物。第47部分。通过6-取代的5-硝基尿嘧啶衍生物的分子内环化反应合成黄嘌呤和吡咯并[3,2- d ]嘧啶的新方法

  摘要：

  通过在三乙胺存在下使6-氯-1,3-二甲基-5-硝基尿嘧啶（1）与芳基烷基胺反应，制得6-芳烷基氨基-1,3-二甲基-5-硝基尿嘧啶（2a–f）。其中，在氮原子和6-芳基烷基氨基部分中的苄基位置不具有取代基的6-芳基烷基氨基尿嘧啶（2a–d）在转化为相应的8-芳基-1,3-二甲基黄嘌呤（3a–d）时在二甲基甲酰胺（DMF）中加热回流。钠盐（反应7 1,3,6-三甲基-5- nitrouracil（的）6）用在无水DMF烷基和芳基烷基卤化物，得到相应的6-（取代甲基）-1,3-二甲基-5-硝基尿嘧啶（8a–j）。其中，对6-（2-芳基乙基）尿嘧啶（8b-f）进行碱催化的环化反应，得到8-芳基-7-羟基-9-脱氮黄嘌呤（9a-e）。另一方面，用三乙胺处理6- [2-（乙氧羰基，乙酰基和氰基）乙基]尿嘧啶（8h-j）导致形成相应的6-乙烯基尿嘧啶（11a-c）。在干燥的DMF中，在碳酸钾的存在下

  DOI：

  10.1039/p19840000583
• 作为产物：
  描述：

  1,3-dimethyl-5-nitro-6-styryluracil 在 tin(ll) chloride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以98%的产率得到5-hydroxy-1,3-dimethyl-6-phenyl-1H-pyrrolo[3,2-d]pyrimidine-2,4(3H,5H)-dione
  参考文献：
  名称：

  1,3-Dialkyl-8-(hetero)aryl-9-OH-9-deazaxanthines as potent A2B adenosine receptor antagonists: Design, synthesis, structure–affinity and structure–selectivity relationships

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2008.09.067

文献信息

• A Facile Synthesis of 7-Hydroxy-9-deazaxanthines
  作者：Kosaku Hirota、Tadashi Sugiyama、Yukio Kitade、Shigeo Senda、Yoshifumi Maki

  DOI：10.1055/s-1982-30088

  日期：——
• HIROTA, KOSAKU;SUGIYAMA, TADASHI;KITADE, YUKIO;SENDA, SHIGEO;MAKI, YOSHIF+, SYNTHESIS, BRD, 1982, N 12, 1097-1099
  作者：HIROTA, KOSAKU、SUGIYAMA, TADASHI、KITADE, YUKIO、SENDA, SHIGEO、MAKI, YOSHIF+

  DOI：——

  日期：——
• HIROTA, KOSAKU;SUGIYAMA, TADASHI;KITADE, YUKIO;SENDA, SHIGEO;MAKI, YOSHIF+, J. CHEM. SOC. PERKIN TRANS., 1984, N 4, 583-588
  作者：HIROTA, KOSAKU、SUGIYAMA, TADASHI、KITADE, YUKIO、SENDA, SHIGEO、MAKI, YOSHIF+

  DOI：——

  日期：——
• Pyrimidine derivatives and related compounds. Part 47. A new synthesis of xanthines and pyrrolo[3,2-d]pyrimidines by intramolecular cyclisation of 6-substituted 5-nitrouracil derivatives
  作者：Kosaku Hirota、Tadashi Sugiyama、Yukio Kitade、Shigeo Senda、Yoshifumi Maki

  DOI：10.1039/p19840000583

  日期：——

  of 6-[2-(ethoxycarbonyl, acetyl, and cyano) ethyl] uracil (8h–j) with triethylamine led to the formation of the corresponding 6-vinyluracil (11 a–c). A one-step synthesis of the 7-hydroxy-9-deazaxanthines (9a–e) was accomplished by the treatment of the sodium salt (7) with arylalkyl chlorides in the presence of potassium carbonate in dry DMF. Deoxygenation of the 7-hydroxy-9-deazaxanthines (9a–e) smoothly

  通过在三乙胺存在下使6-氯-1,3-二甲基-5-硝基尿嘧啶（1）与芳基烷基胺反应，制得6-芳烷基氨基-1,3-二甲基-5-硝基尿嘧啶（2a–f）。其中，在氮原子和6-芳基烷基氨基部分中的苄基位置不具有取代基的6-芳基烷基氨基尿嘧啶（2a–d）在转化为相应的8-芳基-1,3-二甲基黄嘌呤（3a–d）时在二甲基甲酰胺（DMF）中加热回流。钠盐（反应7 1,3,6-三甲基-5- nitrouracil（的）6）用在无水DMF烷基和芳基烷基卤化物，得到相应的6-（取代甲基）-1,3-二甲基-5-硝基尿嘧啶（8a–j）。其中，对6-（2-芳基乙基）尿嘧啶（8b-f）进行碱催化的环化反应，得到8-芳基-7-羟基-9-脱氮黄嘌呤（9a-e）。另一方面，用三乙胺处理6- [2-（乙氧羰基，乙酰基和氰基）乙基]尿嘧啶（8h-j）导致形成相应的6-乙烯基尿嘧啶（11a-c）。在干燥的DMF中，在碳酸钾的存在下
• 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.