8-N-(cyclopropylmethyl)-2-(3,3-dimethylpiperazin-1-yl)-4-N-(2-methylsulfanylphenyl)pyrimido[5,4-d]pyrimidine-4,8-diamine | 1392888-96-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 8-N-(cyclopropylmethyl)-2-(3,3-dimethylpiperazin-1-yl)-4-N-(2-methylsulfanylphenyl)pyrimido[5,4-d]pyrimidine-4,8-diamine
• CAS: 1392888-96-8
• 化学式: C₂₃H₃₀N₈S
• 分子量: 450.611
• InChiKey: VVLUPUQPMLRDDL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  116
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  在 三氟乙酸 作用下， 生成 8-N-(cyclopropylmethyl)-2-(3,3-dimethylpiperazin-1-yl)-4-N-(2-methylsulfanylphenyl)pyrimido[5,4-d]pyrimidine-4,8-diamine
  参考文献：
  名称：

  Pyrimidinopyrimidine inhibitors of ketohexokinase: Exploring the ring C2 group that interacts with Asp-27B in the ligand binding pocket

  摘要：

  Inhibitors of ketohexokinase (KHK) have potential for the treatment of diabetes and obesity. We have continued studies on a pyrimidinopyrimidine series of potent KHK inhibitors by exploring the 2-position substituent (R-3) that interacts with Asp-27B in the ATP-binding region of KHK (viz. 1, 2; Table 1). We found that increased spacing between the terminal ammonium group and the heterocyclic scaffold (viz. 16-20), such that interaction with Asp-27B is not possible, still results in potent KHK inhibition (IC50 = 15-50 nM). We propose a new interaction with Asp-194, which serves to expand the pyrimidinopyrimidine pharmacophore. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.06.008

文献信息

• Pyrimidinopyrimidine inhibitors of ketohexokinase: Exploring the ring C2 group that interacts with Asp-27B in the ligand binding pocket
  作者：Bruce E. Maryanoff、John C. O’Neill、David F. McComsey、Stephen C. Yabut、Diane K. Luci、Alan C. Gibbs、Margery A. Connelly

  DOI：10.1016/j.bmcl.2012.06.008

  日期：2012.8

  Inhibitors of ketohexokinase (KHK) have potential for the treatment of diabetes and obesity. We have continued studies on a pyrimidinopyrimidine series of potent KHK inhibitors by exploring the 2-position substituent (R-3) that interacts with Asp-27B in the ATP-binding region of KHK (viz. 1, 2; Table 1). We found that increased spacing between the terminal ammonium group and the heterocyclic scaffold (viz. 16-20), such that interaction with Asp-27B is not possible, still results in potent KHK inhibition (IC50 = 15-50 nM). We propose a new interaction with Asp-194, which serves to expand the pyrimidinopyrimidine pharmacophore. (C) 2012 Elsevier Ltd. All rights reserved.