7-hydroxy-1-methyl-6-(4-(methylsulfonyl)phenyl)-3-propyl-1H-pyrrolo[3,2-d]pyrimidine-2,4(3H,5H)-dione | 1084328-40-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 7-hydroxy-1-methyl-6-(4-(methylsulfonyl)phenyl)-3-propyl-1H-pyrrolo[3,2-d]pyrimidine-2,4(3H,5H)-dione
• 英文别名: 7-hydroxy-1-methyl-6-(4-methylsulfonylphenyl)-3-propyl-5H-pyrrolo[3,2-d]pyrimidine-2,4-dione
• CAS: 1084328-40-4
• 化学式: C₁₇H₁₉N₃O₅S
• 分子量: 377.421
• InChiKey: KUPQOGCWMSZCTA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  119
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1,6-Dimethyl-5-nitro-3-propylpyrimidine-2,4(1H,3H)-dione 、 对甲砜基苯甲醛 在 哌啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.25h， 以68%的产率得到7-hydroxy-1-methyl-6-(4-(methylsulfonyl)phenyl)-3-propyl-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

• 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.