4-(9-([1,1'-biphenyl]-4-ylmethyl)-8-ethyl-9H-purin-6-yl)morpholine

• 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: 4-(9-([1,1'-biphenyl]-4-ylmethyl)-8-ethyl-9H-purin-6-yl)morpholine
• 英文别名: 4-[8-Ethyl-9-[(4-phenylphenyl)methyl]purin-6-yl]morpholine；4-[8-ethyl-9-[(4-phenylphenyl)methyl]purin-6-yl]morpholine
• 化学式: C₂₄H₂₅N₅O
• 分子量: 399.495
• InChiKey: SBTGPRGZHRBZSZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  56.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  6-氯-8-乙基-9H-嘌呤 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 4-(9-([1,1'-biphenyl]-4-ylmethyl)-8-ethyl-9H-purin-6-yl)morpholine
  参考文献：
  名称：

  Design and optimization of purine derivatives as in vivo active PDE10A inhibitors

  摘要：

  Phosphodiesterases are important enzymes regulating signal transduction mediated by second messenger molecules cAMP or cGMP. PDE10A is a unique member in the PDE family because of its selective expression in medium spiny neurons. It is recognized as anti-psychotic drug target. Based on the structural similarity between our previous chemistry work on 8-aminoimidazo[1,2-alpyrazines and the PDE10A inhibitors reported by Bartolome-Nebreda et al., we initialized a project for developing PDE10A inhibitors. After several rounds of optimization, we were able to obtain a few compounds with good PDE10A enzymatic activity. And after further PDE enzymatic selectivity study, metabolic stability assay and in vivo pharmacological tests we identified two inhibitors as interesting lead compounds with the potential for further PDE10A lead optimizatioin. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.04.019

文献信息

• Design and optimization of purine derivatives as in vivo active PDE10A inhibitors
  作者：Liu Chen、Danqi Chen、Le Tang、Jing Ren、Jiaojiao Chen、Xuechu Zhen、Yu-Chih Liu、Chenhua Zhang、Haibin Luo、Jingkang Shen、Bing Xiong

  DOI：10.1016/j.bmc.2017.04.019

  日期：2017.7

  Phosphodiesterases are important enzymes regulating signal transduction mediated by second messenger molecules cAMP or cGMP. PDE10A is a unique member in the PDE family because of its selective expression in medium spiny neurons. It is recognized as anti-psychotic drug target. Based on the structural similarity between our previous chemistry work on 8-aminoimidazo[1,2-alpyrazines and the PDE10A inhibitors reported by Bartolome-Nebreda et al., we initialized a project for developing PDE10A inhibitors. After several rounds of optimization, we were able to obtain a few compounds with good PDE10A enzymatic activity. And after further PDE enzymatic selectivity study, metabolic stability assay and in vivo pharmacological tests we identified two inhibitors as interesting lead compounds with the potential for further PDE10A lead optimizatioin. (C) 2017 Elsevier Ltd. All rights reserved.