5,6-diamino-1-(4-methoxy-benzyl)-3-methyl-1H-pyrimidine-2,4-dione | 54099-72-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 5,6-diamino-1-(4-methoxy-benzyl)-3-methyl-1H-pyrimidine-2,4-dione
• 英文别名: 5,6-Diamino-1-[(4-methoxyphenyl)methyl]-3-methyl-2,4(1h,3h)-pyrimidinedione；5,6-diamino-1-[(4-methoxyphenyl)methyl]-3-methylpyrimidine-2,4-dione
• CAS: 54099-72-8
• 化学式: C₁₃H₁₆N₄O₃
• 分子量: 276.295
• InChiKey: FVGUNKODVMXRRZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.23
• 重原子数：
  20.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  105.27
• 氢给体数：
  2.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  5,6-diamino-1-(4-methoxy-benzyl)-3-methyl-1H-pyrimidine-2,4-dione 在 potassium carbonate 、 三氟乙酸 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 生成 8-ethyl-7-(4-heptyl)-1-methyl-3,7-dihydro-1H-purine-2,6-dione
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of 1,2,3,7-Tetrahydro-6H-purin-6-one and 3,7-Dihydro-1H-purine-2,6-dione Derivatives as Corticotropin-Releasing Factor₁ Receptor Antagonists

  摘要：

  A growing body of evidence suggests that CRF1, receptor antagonism offers considerable therapeutic potential in the treatment of diseases resulting from elevated levels of CRF, such as anxiety and depression. A series of novel 1,2,3,7-tetrahydro-6H-purin-6-one and 3,7-dihydro-1H-purine-2,6-dione derivatives was synthesized and evaluated as corticotropin releasing factor-1 (CRF1) receptor antagonists. Compounds within this series, represented by compound 12d (IC50 = 5.4 nM), were found to be highly potent CRF, receptor antagonists. In addition, compounds 12d and 12j were determined to be selective CRF, antagonists. The synthesis, structure-activity relationships and pharmacokinetic properties of compounds within this series is presented.

  DOI：

  10.1021/jm049787k
• 作为产物：
  描述：

  1-[(4-Methoxyphenyl)methyl]-3-methylurea 在 ammonium hydroxide 、 sodium dithionite 、 乙酸酐 、 溶剂黄146 、 sodium nitrite 作用下， 生成 5,6-diamino-1-(4-methoxy-benzyl)-3-methyl-1H-pyrimidine-2,4-dione
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of 1,2,3,7-Tetrahydro-6H-purin-6-one and 3,7-Dihydro-1H-purine-2,6-dione Derivatives as Corticotropin-Releasing Factor₁ Receptor Antagonists

  摘要：

  A growing body of evidence suggests that CRF1, receptor antagonism offers considerable therapeutic potential in the treatment of diseases resulting from elevated levels of CRF, such as anxiety and depression. A series of novel 1,2,3,7-tetrahydro-6H-purin-6-one and 3,7-dihydro-1H-purine-2,6-dione derivatives was synthesized and evaluated as corticotropin releasing factor-1 (CRF1) receptor antagonists. Compounds within this series, represented by compound 12d (IC50 = 5.4 nM), were found to be highly potent CRF, receptor antagonists. In addition, compounds 12d and 12j were determined to be selective CRF, antagonists. The synthesis, structure-activity relationships and pharmacokinetic properties of compounds within this series is presented.

  DOI：

  10.1021/jm049787k

文献信息

• 8-Aryl xanthines potent inhibitors of phosphodiesterase 5
  作者：Ruth Arnold、David Beer、Gurdip Bhalay、Urs Baettig、Stephen P Collingwood、Sarah Craig、Nicholas Devereux、Andrew Dunstan、Angela Glen、Sylvie Gomez、Sandra Haberthuer、Trevor Howe、Stephen Jelfs、Heinz Moser、Reto Naef、Paul Nicklin、David Sandham、Rowan Stringer、Katharine Turner、Simon Watson、Mauro Zurini

  DOI：10.1016/s0960-894x(02)00480-8

  日期：2002.9

  In clinical studies, several inhibitors of phosphodiesterase 5 (PDE5) have demonstrated utility in the treatment of erectile dysfunction. We describe herein a series of 8-aryl xanthine derivatives which function as potent PDE5 inhibitors with, in many cases, high levels of selectivity versus other PDE isoforms. (C) 2002 Elsevier Science Ltd. All rights reserved.