2-amino-5H-indeno[1,2-d]pyrimidin-4-ol

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 2-amino-5H-indeno[1,2-d]pyrimidin-4-ol
• 英文别名: 2-Amino-3,5-dihydroindeno[1,2-d]pyrimidin-4-one；2-amino-3,5-dihydroindeno[1,2-d]pyrimidin-4-one
• 化学式: C₁₁H₉N₃O
• 分子量: 199.212
• InChiKey: LPOIYANPELPYBS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  67.5
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-amino-5H-indeno[1,2-d]pyrimidin-4-ol 、 对硝基苯磺酰氯 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 以20%的产率得到2-amino-5H-indeno[1,2-d]pyrimidin-4-yl 4-nitrobenzenesulfonate
  参考文献：
  名称：

  Rotationally Constrained 2,4-Diamino-5,6-disubstituted Pyrimidines: A New Class of Histamine H₄ Receptor Antagonists with Improved Druglikeness and in Vivo Efficacy in Pain and Inflammation Models

  摘要：

  A new structural class of histamine H-4 receptor antagonists (6-14) was designed based on rotationally restricted 2,4-diaminopyrimidines. Series compounds showed potent and selective in vitro H-4 antagonism across multiple species, good CNS penetration, improved PK properties compared to reference H-4 antagonists, functional H-4 antagonism in cellular and in vivo pharmacological assays, and in vivo anti-inflammatory and antinociceptive efficacy. One compound, 10 (A-943931), combined the best features of the series in a single molecule and is an excellent tool compound to probe H-4 pharmacology. It is a potent H-4 antagonist in functional assays across species (FLIPR Ca2+ flux, K-b < 5.7 nM), has high (> 190x) selectivity for H-4, and combines good PK in rats and mice (t(1/2) of 2.6 and 1.6 h, oral bioavailability of 37% and 90%) with anti-inflammatory activity (ED50 = 37 mu mol/kg, mouse) and efficacy in pain models (thermal hyperalgesia, ED50 = 72 mu mol/kg, rat).

  DOI：

  10.1021/jm800670r
• 作为产物：
  描述：

  1H-茚-2-甲酸,2,3-二氢-1-氧代-,甲酯 、 碳酸胍 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.1h， 以11%的产率得到2-amino-5H-indeno[1,2-d]pyrimidin-4-ol
  参考文献：
  名称：

  Rotationally Constrained 2,4-Diamino-5,6-disubstituted Pyrimidines: A New Class of Histamine H₄ Receptor Antagonists with Improved Druglikeness and in Vivo Efficacy in Pain and Inflammation Models

  摘要：

  A new structural class of histamine H-4 receptor antagonists (6-14) was designed based on rotationally restricted 2,4-diaminopyrimidines. Series compounds showed potent and selective in vitro H-4 antagonism across multiple species, good CNS penetration, improved PK properties compared to reference H-4 antagonists, functional H-4 antagonism in cellular and in vivo pharmacological assays, and in vivo anti-inflammatory and antinociceptive efficacy. One compound, 10 (A-943931), combined the best features of the series in a single molecule and is an excellent tool compound to probe H-4 pharmacology. It is a potent H-4 antagonist in functional assays across species (FLIPR Ca2+ flux, K-b < 5.7 nM), has high (> 190x) selectivity for H-4, and combines good PK in rats and mice (t(1/2) of 2.6 and 1.6 h, oral bioavailability of 37% and 90%) with anti-inflammatory activity (ED50 = 37 mu mol/kg, mouse) and efficacy in pain models (thermal hyperalgesia, ED50 = 72 mu mol/kg, rat).

  DOI：

  10.1021/jm800670r

文献信息

• Rotationally Constrained 2,4-Diamino-5,6-disubstituted Pyrimidines: A New Class of Histamine H₄ Receptor Antagonists with Improved Druglikeness and in Vivo Efficacy in Pain and Inflammation Models
  作者：Marlon D. Cowart、Robert J. Altenbach、Huaqing Liu、Gin C. Hsieh、Irene Drizin、Ivan Milicic、Thomas R. Miller、David G. Witte、Neil Wishart、Shannon R. Fix-Stenzel、Michael J. McPherson、Ronald M. Adair、Jill M. Wetter、Brian M. Bettencourt、Kennan C. Marsh、James P. Sullivan、Prisca Honore、Timothy A. Esbenshade、Jorge D. Brioni

  DOI：10.1021/jm800670r

  日期：2008.10.23

  A new structural class of histamine H-4 receptor antagonists (6-14) was designed based on rotationally restricted 2,4-diaminopyrimidines. Series compounds showed potent and selective in vitro H-4 antagonism across multiple species, good CNS penetration, improved PK properties compared to reference H-4 antagonists, functional H-4 antagonism in cellular and in vivo pharmacological assays, and in vivo anti-inflammatory and antinociceptive efficacy. One compound, 10 (A-943931), combined the best features of the series in a single molecule and is an excellent tool compound to probe H-4 pharmacology. It is a potent H-4 antagonist in functional assays across species (FLIPR Ca2+ flux, K-b < 5.7 nM), has high (> 190x) selectivity for H-4, and combines good PK in rats and mice (t(1/2) of 2.6 and 1.6 h, oral bioavailability of 37% and 90%) with anti-inflammatory activity (ED50 = 37 mu mol/kg, mouse) and efficacy in pain models (thermal hyperalgesia, ED50 = 72 mu mol/kg, rat).