4-(5-methylfuran-2-yl)-6-[3-(morpholine-4-carbonyl)phenyl]pyrimidin-2-amine

• 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: 4-(5-methylfuran-2-yl)-6-[3-(morpholine-4-carbonyl)phenyl]pyrimidin-2-amine
• 英文别名: [3-[2-Amino-6-(5-methylfuran-2-yl)pyrimidin-4-yl]phenyl]-morpholin-4-ylmethanone；[3-[2-amino-6-(5-methylfuran-2-yl)pyrimidin-4-yl]phenyl]-morpholin-4-ylmethanone
• 化学式: C₂₀H₂₀N₄O₃
• 分子量: 364.404
• InChiKey: QIFBQOZLXFZMLD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  94.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3-羧基苯甲醛 在 水 、 sodium hydride 、 N,N'-羰基二咪唑 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 53.0h， 生成 4-(5-methylfuran-2-yl)-6-[3-(morpholine-4-carbonyl)phenyl]pyrimidin-2-amine
  参考文献：
  名称：

  2-Aminopyrimidines as dual adenosine A1/A2A antagonists

  摘要：

  In this study thirteen 2-aminopyrimidine derivatives were synthesised and screened as potential antagonists of adenosine A(1) and A(2A) receptors in order to further investigate the structure activity relationships of this class of compounds. 4-(5-Methylfuran-2-yl)-6[3-(piperidine-1-carbonyl)phenyl] pyrimidin-2-amine (8m) was identified as a compound with high affinities for both receptors, with an A(2A)Ki value of 6.34 nM and an A(1)Ki value of 9.54 nM. The effect of selected compounds on the viability of cultured cells was assessed and preliminary results indicate low cytotoxicity. In vivo efficacy at A(2A) receptors was illustrated for compounds 8k and 8m since these compounds attenuated haloperidol-induced catalepsy in rats. A molecular docking study revealed that the interactions between the synthesised compounds and the adenosine A2A binding site most likely involve Phe168 and Asn253, interactions which are similar for structurally related adenosine A(2A) receptor antagonists. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.09.035

文献信息

• 2-Aminopyrimidines as dual adenosine A1/A2A antagonists
  作者：Sarel J. Robinson、Jacobus P. Petzer、Gisella Terre’Blanche、Anél Petzer、Mietha M. van der Walt、Jacobus J. Bergh、Anna C.U. Lourens

  DOI：10.1016/j.ejmech.2015.09.035

  日期：2015.11

  In this study thirteen 2-aminopyrimidine derivatives were synthesised and screened as potential antagonists of adenosine A(1) and A(2A) receptors in order to further investigate the structure activity relationships of this class of compounds. 4-(5-Methylfuran-2-yl)-6[3-(piperidine-1-carbonyl)phenyl] pyrimidin-2-amine (8m) was identified as a compound with high affinities for both receptors, with an A(2A)Ki value of 6.34 nM and an A(1)Ki value of 9.54 nM. The effect of selected compounds on the viability of cultured cells was assessed and preliminary results indicate low cytotoxicity. In vivo efficacy at A(2A) receptors was illustrated for compounds 8k and 8m since these compounds attenuated haloperidol-induced catalepsy in rats. A molecular docking study revealed that the interactions between the synthesised compounds and the adenosine A2A binding site most likely involve Phe168 and Asn253, interactions which are similar for structurally related adenosine A(2A) receptor antagonists. (C) 2015 Elsevier Masson SAS. All rights reserved.