1-(4-methoxyphenyl)-3-[4-({4-oxo-2H,4H,5H-pyrazolo[3,4-d]pyrimidin-2-yl}methyl)phenyl]urea | 1126894-01-6

• 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-(4-methoxyphenyl)-3-[4-({4-oxo-2H,4H,5H-pyrazolo[3,4-d]pyrimidin-2-yl}methyl)phenyl]urea
• 英文别名: 1-(4-methoxyphenyl)-3-[4-[(4-oxo-5H-pyrazolo[3,4-d]pyrimidin-2-yl)methyl]phenyl]urea
• CAS: 1126894-01-6
• 化学式: C₂₀H₁₈N₆O₃
• 分子量: 390.401
• InChiKey: YGXUTTFHTNBHCM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  107
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-(4-aminobenzyl)-2H-pyrazolo[3,4-d]pyrimidin-4(5H)-one 、 对甲氧基苯异氰酸酯 反应 0.17h， 以49%的产率得到1-(4-methoxyphenyl)-3-[4-({4-oxo-2H,4H,5H-pyrazolo[3,4-d]pyrimidin-2-yl}methyl)phenyl]urea
  参考文献：
  名称：

  Exploiting the Pyrazolo[3,4-d]pyrimidin-4-one Ring System as a Useful Template To Obtain Potent Adenosine Deaminase Inhibitors

  摘要：

  A number of pyrazolo[3,4-d]pyrimidin-4-ones bearing either alkyl or arylalkyl substituents in position 2 of the nucleus were synthesized and tested for their ability to inhibit adenosine deaminase (ADA) from bovine spleen. The 2-arylalkyl derivatives exhibited excellent inhibitory activity, showing K-i values in the nanomolar/subnanomolar range. The most active compound, 1-(4-((4-oxo-4,5-dihydropyrazolo[3,4-d]pyrimidin-2-yl)methyl)phenyl)-3-(4-(trifluoromethyl)phenyl)urea, 14d, was tested in rats with colitis induced by 2,4-dinitrobenzenesulfonic acid to assess its efficacy to attenuate bowel inflammation. The treatment with 14d induced a significant amelioration of both systemic and intestinal inflammatory alterations in animals with experimental colitis. Docking simulations of the synthesized compounds into the ADA catalytic site were also performed to rationalize the structure-activity relationships observed and to highlight the key pharmacophoric elements of these products, thus prospectively guiding the design of novel ADA inhibitors.

  DOI：

  10.1021/jm801427r

文献信息

• Exploiting the Pyrazolo[3,4-<i>d</i>]pyrimidin-4-one Ring System as a Useful Template To Obtain Potent Adenosine Deaminase Inhibitors
  作者：Concettina La Motta、Stefania Sartini、Laura Mugnaini、Silvia Salerno、Francesca Simorini、Sabrina Taliani、Anna Maria Marini、Federico Da Settimo、Antonio Lavecchia、Ettore Novellino、Luca Antonioli、Matteo Fornai、Corrado Blandizzi、Mario Del Tacca

  DOI：10.1021/jm801427r

  日期：2009.3.26

  A number of pyrazolo[3,4-d]pyrimidin-4-ones bearing either alkyl or arylalkyl substituents in position 2 of the nucleus were synthesized and tested for their ability to inhibit adenosine deaminase (ADA) from bovine spleen. The 2-arylalkyl derivatives exhibited excellent inhibitory activity, showing K-i values in the nanomolar/subnanomolar range. The most active compound, 1-(4-((4-oxo-4,5-dihydropyrazolo[3,4-d]pyrimidin-2-yl)methyl)phenyl)-3-(4-(trifluoromethyl)phenyl)urea, 14d, was tested in rats with colitis induced by 2,4-dinitrobenzenesulfonic acid to assess its efficacy to attenuate bowel inflammation. The treatment with 14d induced a significant amelioration of both systemic and intestinal inflammatory alterations in animals with experimental colitis. Docking simulations of the synthesized compounds into the ADA catalytic site were also performed to rationalize the structure-activity relationships observed and to highlight the key pharmacophoric elements of these products, thus prospectively guiding the design of novel ADA inhibitors.